Consortium for Infection- and Immune-Mediated Movement Disorders in India: A Call to Action for Collaborative Discovery and Care
Year: 2025
Type: article
Abstract: Introduction Movement disorders arising from infectious and immune-mediated causes represent an important yet under-recognized group of potentially treatable neurological conditions. These include infection-mediated movement disorders (InMD), which occur in the context of systemic or central nervous system infections,[1] and immune-mediated movement disorders (ImMD), which result from aberrant immune responses affecting the nervous system and may encompass both autoinflammatory and autoimmune conditions.[2] The latter two conditions are distinct immune entities. Autoimmune disorders involve the adaptive immune system and cause self-damage through the development of autoantibodies. Autoinflammatory conditions arise from dysregulation of the innate immune system, leading to unprovoked episodes of inflammation without the development of autoantibodies. These are rare monogenetic disorders that are well recognized as being triggered by infections.[3] These movement disorders, though distinct in etiology, often share overlapping clinical features and may even co-exist or evolve from one another.[4] Infections can trigger or modulate the immune response; for instance, ant- N-methyl-D-aspartate receptor encephalitis may be triggered by herpesvirus encephalitis. The immune system responds to eliminate pathogens, which can result in aberrant cross-reactivity. Both processes outlined above share common pathways mediated through innate and acquired immune mechanisms. Importantly, both are potentially treatable, and early recognition is known to significantly improve patient outcomes. InMD may account for up to 5.3% of movement disorders overall and up to 28% of acquired movement disorders,[5,6] particularly in low- and middle-income countries (LMICs), where infectious diseases remain highly prevalent. ImMD, meanwhile, represent a rapidly expanding frontier, with the discovery of several novel autoantibodies, particularly over the past two decades, transforming our understanding of movement disorder syndromes within the autoimmune spectrum. These disorders include autoimmune hypo- and hyperkinetic movement disorders and ataxias, paraneoplastic movement disorders, stiff-person spectrum disorders, and movement disorders arising in the context of systemic immune conditions. The global landscape of these conditions is evolving rapidly. Emerging and re-emerging infections, such as Severe acute respiratory syndrome coronavirus 2, Zika, measles, dengue and chikungunya,[7] highlight the capacity of infectious agents to trigger para- and post-infectious neurological syndromes, including movement disorders. Simultaneously, the increasing availability of antibody testing and advanced imaging has revealed a wide spectrum of autoimmune movement disorders, many of which were previously misclassified or undiagnosed. Despite this momentum, which is also evident in India, these disorders remain under-prioritized in clinical neurology, particularly in LMICs such as India, where the burden is likely to be disproportionately high due to endemic infections, limited resources, and diagnostic challenges. The lack of standardized approaches, epidemiological data, or collaborative networks hampers both clinical care and research. Cost concerns related to diagnostic testing, such as autoimmune panels, the limited availability of specific tests like cell-based assays, and treatment continue to pose challenges in our setting.[8] Indian Context India represents a unique confluence of infectious and immune-mediated diseases, making it an epicenter for disorders at the intersection of infection, immunity, and neurology. Endemic infections such as tuberculosis (TB), neurocysticercosis (NCC), dengue, malaria, chikungunya, and human immunodeficiency virus frequently affect the nervous system, often resulting in secondary movement disorders.[9-14] Streptococcal infections remain highly relevant in India, with Sydenham’s chorea continuing to be a major cause of childhood-onset movement disorders. This post-streptococcal autoimmune phenomenon presents with chorea, behavioral changes, and emotional lability, often occurring in the context of rheumatic fever. Early recognition and treatment of group A streptococcal infections are therefore critical to reducing their burden. Similarly, neurosyphilis—although less common today—can manifest with a variety of movement disorders, including chorea, ataxia, tremor, dystonia, and parkinsonism, reflecting the diverse neurotropic effects of Treponema pallidum.[15-17] Additionally, subacute sclerosing panencephalitis (SSPE) and Japanese encephalitis (JE) continue to be public health concerns across many regions of the country. The emergence of Nipah virus[18] and scrub typhus,[19] and the re-emergence of West Nile virus,[18] further underscore the evolving infectious landscape in India. Studies from India indicate that movement disorders may affect up to 65% of patients with JE and up to 56% of patients with SSPE (excluding myoclonus),[11,12] although data remain lacking for several other conditions, emphasizing both the high burden and the potential for further research. Infectious diseases and their associated movement disorders, which are commonly encountered in India, are rarely seen in high-income countries, leading to gaps in global recognition, guidelines, and research focus on these conditions. Some infections exhibit distinct geographic patterns within the country. For instance, JE is more common in parts of eastern Uttar Pradesh and Bihar, while scrub typhus is endemic to the Himalayan foothills and the northeastern and southern Indian states.[20] It is also notable that several infections engendering InMD may be preventable or treatable if addressed early in the disease course. SSPE has declined in several countries with improved measles vaccination coverage, yet gaps in immunization leave vulnerable populations at risk. Similarly, broader implementation of varicella vaccination could help reduce post-varicella neurological sequelae. Sydenham’s chorea, linked to untreated group A streptococcal infections, persists as an important cause of childhood disability, especially in rural and underserved areas where timely diagnosis and access to antibiotics may be inadequate. Early recognition and treatment of streptococcal infections, along with the timely initiation of immunomodulatory or symptomatic therapies in Sydenham’s chorea, can mitigate disease severity and long-term sequelae.[21] Strengthening routine immunization programs, closing coverage gaps, and ensuring early treatment of common infections are critical public health strategies to reduce the burden of these preventable movement disorders in India. Climate change, urbanization, and changing land-use patterns, observed both globally and nationally,[22] are accelerating the spread of many vector-borne and zoonotic infections. These shifts are likely to expand the burden of infection-related neurological complications,[23] including movement disorders, for which preparedness is crucial. Specific predicted changes due to rising temperatures, increased rainfall, and higher humidity include vector range expansion, increased vector longevity, and altered biting patterns, all of which have specific connotations for the potential rise in vector-borne diseases in India and associated InMD. While improved access to diagnostic tools, such as autoantibody panels and advanced neuroimaging, has led to growing recognition of ImMD across the country, these disorders remain challenging to diagnose and treat.[8] Commonly encountered antibodies include anti-NMDAR, often associated with choreoathetosis and dyskinesias in children and young adults, whereas antibodies such as anti-LGI1, contactin associated protein-like 2, and glutamic acid decarboxylase 65 may rarely present with myoclonus, dystonia, or stiff-person spectrum disorders.[24] The diagnostic challenge lies in differentiating these syndromes from infectious or metabolic mimics, a task compounded by limited access to antibody panels in many regions. The validity and standardization of assays vary widely, and antibodies of uncertain or unknown clinical significance[25,26] are often reported, creating diagnostic dilemmas. Unclassified neuronal antibodies add further complexity, and in some instances, treatment is initiated empirically on the assumption of immune-mediated disease, raising concerns about unnecessary immunotherapy exposure and cost. These issues underscore the importance of judicious antibody testing, careful clinicoradiological correlation, and the timely initiation of therapy only when appropriate, to optimize outcomes in patients with suspected ImMD in India. Therapeutically, timely initiation of immunotherapy can be highly effective, but delays in diagnosis often result in prolonged morbidity. Expanding access to reliable antibody testing and integrating these disorders into the differential diagnosis of acute and subacute movement disorders will be essential for improving outcomes in the Indian setting. Another challenge is investigating undiagnosed cases with the aim of identifying newer antibodies, which will necessitate collaboration with, and the development of, basic science expertise in the future. However, despite this high burden and growing clinical recognition, India lacks a comprehensive national strategy to address these disorders. This gap may potentially contribute to delayed diagnosis, inappropriate treatment, poor outcomes, and inefficient utilization of resources. Many centers function in isolation, and the absence of coordinated research efforts has resulted in fragmented data and variable clinical practices. Moreover, co-existing infections and immune dysfunction often pose unique diagnostic and therapeutic dilemmas in Indian patients— for example, the use of immunotherapy in the context of latent TB or endemic parasitic infections. Additional challenges include diagnosing and treating autoimmune diseases in the context of immune dysregulation syndromes. These clinical challenges are currently being managed by clinicians across the country in a heterogeneous manner. Prevailing gaps and Felt Needs Despite the considerable burden of InMD and ImMD, there is a striking lack of cohesive clinical strategies and consolidated national data from India. Many of the infections seen in India have well-recognized neurological manifestations, including movement disorders. Despite this, the true prevalence of InMD in India remains poorly quantified. While some specialty clinics report a burden as high as 28% of secondary movement disorders,[5] there are no standardized diagnostic pathways or treatment paradigms for InMD, despite the existence of several guidelines for neuroinfections, and long-term outcome data remain scarce, potentially impacting patient care and research prioritization. In India, the diagnosis of InMD and ImMD is often hampered by limited access to autoimmune antibody panels, cerebrospinal fluid studies, and advanced neuroimaging, particularly in rural and secondary care settings. There is a pressing need to develop India-specific diagnostic protocols that incorporate locally prevalent infections such as TB, JE, and NCC. Adopting tiered diagnostic algorithms tailored to varying resource levels can facilitate appropriate and efficient evaluation, improve early detection, and standardize care across diverse healthcare settings. India-specific guidelines and research are also important due to certain specific factors such as genetics, gut microbiome differences, and the profile of chronic infections, which may contribute to the spectrum of InMD and ImMD seen in India, thereby creating a unique avenue for research. For ImMD, the challenge is even more pronounced. Although a growing number of autoimmune movement disorders are being recognized globally, India lacks systematic studies or registries to reflect this evolving landscape. Published data remain largely limited to small case series and single-center experiences.[24] Furthermore, the interaction between infections and immune responses—particularly relevant in low- and middle-income settings such as India—is not well characterized. Currently, India has no dedicated national consortium addressing either InMD or ImMD. While an international study group under the International Parkinson and Movement Disorder Society (MDS) exists for infection-related movement disorders (IRMD study group), there is no equivalent group for ImMD at either the national or international level, nor for InMD at the national level. Notably, a recent survey by the MDS IRMD study group showed a very high response rate (70.5%) from India, emphasizing both a higher burden and significant interest among Indian neurologists (unpublished data) in the field of InMD. Thus, there is a critical need for a unified, collaborative platform that can: Generate multicenter epidemiological data Develop context-specific clinical guidelines Foster interdisciplinary collaboration Amplify awareness and advocacy for these treatable disorders The Consortium for Infection- and Immune-Mediated Movement Disorders in India (CIIMDI) was conceived in direct response to these gaps, recognizing the urgent need for a structured, multicentric, interdisciplinary approach to address these challenges—bringing together neurologists, infectious disease experts, immunologists, and other stakeholders to foster collaboration in this vital area. CIIMDI: Genesis, Aim, and Objectives CIIMDI was formally initiated on 22 May 2025 under the aegis of the Movement Disorders Society of India (MDSI). The aim of CIIMDI is to establish a consortium of movement disorder neurologists and allied specialists who are interested and active in the field of InMD and ImMD, with the goal of promoting advocacy, teaching, and research. CIIMDI has the following specific objectives: To establish a national and international network of movement disorder neurologists interested in the field of InMD and ImMD. To generate large-scale national and international data on the frequency, spectrum, and outcomes of InMD and ImMD. To generate India-specific guidelines on diagnosis and treatment, taking resource constraints into account. To increase awareness among physicians, neurologists, and movement disorder specialists about InMD and ImMD. To advocate for individuals affected by and living with InMD and ImMD and their care-partners. To partner with other groups working in InMD and ImMD, including infectious disease specialists, microbiologists, pathologists, radiologists, oncologists, autoimmune neurology groups, geneticists, basic scientists, and industry-partners. To collaborate with other LMICs with similar infection patterns and with the MDS-Asia-Oceania section. To focus on disorders more prevalent in the pediatric age group, such as SSPE, autoimmune encephalitis (e.g., anti-NMDAR), and post-infectious movement disorders (e.g., Sydenham’s chorea). To develop capacity- building initiatives for healthcare workers across different levels of healthcare (primary, secondary, tertiary). Outlook The CIIMDI is founded on three pillars that guide its core activities, namely research, teaching and knowledge exchange, and advocacy. CIIMDI envisions strategic growth aimed at establishing a strengthened ecosystem for InMD and ImMD in India. The short-, medium-, and long-term goals of CIIMDI are outlined in Table 1.Table 1: Proposed strategic timeline of focus areas and key goals of CIIMDI in SMART formatOne of the key areas of focus will be multicentric collaborative research, with the overarching aim of generating high-quality, standardized and comprehensive national data to accelerate clinical and translational discovery. A crucial strategy will be to facilitate interdisciplinary collaboration with diverse associated specialties, such as infectious diseases, immunology, radiology, microbiology, genetics and others, to garner multidimensional perspectives and strengthen innovative discovery. Securing long-term funding for CIIMDI will be a key priority to maintain research momentum and drive impactful outcomes. Developing standardized national clinical care pathways for high-priority conditions such as SSPE, TB- and JE-associated movement disorders, and ImMD will be a critical and timely initiative. To facilitate teaching and cross-learning, CIIMDI will conduct video-based case discussions, in partnership with and leveraging the ongoing MDSI case discussion efforts under the Rare Movement Disorders consortium and the MDSI Fellows meeting. A video repository of cases is planned to serve as a learning reservoir, accessible through the MDSI platform. As part of its advocacy efforts, CIIMDI will collaborate with public health agencies, patient organizations, and global partners to drive awareness and influence policy change. Online educational materials for patients and their care-partners will be developed and made available across MDSI platforms. Potential challenges that CIIMDI may encounter include securing and sustaining research funding, inter-institutional coordination, and data sharing agreements. However, these challenges are surmountable through strategic planning, effective relationship management, and administrative rigor. CIIMDI aims to address funding constraints by diversifying its funding portfolio, aligning strategically with national and international research priorities, promoting collaborative grant writing, and implementing sustainability planning. MDSI, as the parent body of CIIMDI, will be leveraged for potential intramural and extramural research grants. Interinstitutional coordination may be strengthened through regular communication, conflict resolution planning, and the appointment of designated liaisons. Additionally, the use of standardized data-sharing agreements, secure data platforms, and proactive engagement with ethics boards will help address challenges pertaining to data sharing. Conclusion InMD and ImMD represent a critical, yet historically neglected, frontier in neurology—especially in the Indian context, where infectious diseases remain endemic, and immune dysfunction is increasingly recognized. The CIIMDI emerges as a timely and essential initiative to bridge existing gaps through interdisciplinary collaboration, robust data generation, education, and advocacy. By amalgamating stakeholders across neurology, infectious diseases, immunology, and public health, CIIMDI aspires to build a resilient and responsive ecosystem that prioritizes early diagnosis, equitable care, and innovative research. The vision is clear: to transform these treatable but often overlooked disorders from isolated clinical encounters into nationally recognized priorities. In doing so, CIIMDI not only aims to improve individual patient outcomes but also to redefine the broader landscape of movement disorders in India. We call upon clinicians, researchers, policymakers, and patient advocates to join hands in this collective mission—toward a future where no patient with a treatable movement disorder is left undiagnosed or untreated. Author contribution A. Research project: Conception: Divyani Garg, Vijayashankar Paramanandam Organization: Divyani Garg, Vijayashankar Paramanandam Execution: Divyani Garg, Vijayashankar Paramanandam B. Statistical analysis: Design: None Execution: None Review and Critique: None C. Manuscript preparation Writing of the first draft: Divyani Garg Review and Critique: Vijayashankar Paramanandam, Adreesh Mukherjee, Kartika Gulati, Vikram V Holla, Jacky Ganguly, Niraj Kumar, Ravi Yadav, Soaham Desai, Charulata Sankhla, Pramod Kumar Pal Ethical compliance statement We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
Source: Annals of Movement Disorders
Authors: Divyani Garg, Vijayashankar Paramanandam, Adreesh Mukherjee, Kartika Gulati, Vikram V Holla, Jacky Ganguly, Niraj Kumar, Ravi Yadav, Soaham Desai, Charulata Sankhla, Pramod K. Pal
Institutions: All India Institute of Medical Sciences, Apollo Hospitals, North Bengal Medical College and Hospital, Paras Hospitals, National Institute of Mental Health and Neurosciences, Institute of Neurosciences Kolkata, All India Institute of Medical Sciences Bibinagar, Pramukhswami Medical College, P. D. Hinduja Hospital and Medical Research Centre
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7108474156