Motor neuron disease (MND) is a group of progressive neurodegenerative disorders characterized by the degeneration of motor neurons, resulting in muscle weakness, atrophy, and eventual paralysis. The most common form is amyotrophic lateral sclerosis (ALS), which presents with both upper and lower motor neuron signs, while other forms such as progressive muscular atrophy (PMA) and primary lateral sclerosis (PLS) present predominantly with lower or upper motor neuron involvement, respectively [1,2]. The clinical course of MND is highly variable. ALS typically progresses rapidly, leading to significant morbidity and mortality within a few years of onset. In contrast, PMA and PLS often have a slower, more indolent course [3]. Long-term studies on MND, especially in India, are limited, and data on disease progression, survival outcomes, and clinical patterns remain scarce [4]. This study aims to provide a comprehensive analysis of 30 cases of MND over a ten-year period, focusing on clinical presentation, disease progression, and survival patterns. By evaluating these cases, we aim to enhance understanding of MND’s natural history and inform clinical management strategies in the Indian context.

This was a hospital-based, prospective observational study conducted in the Department of Neurology over a period of ten years, from January 2015 to January 2025. A total of 30 clinically diagnosed cases of motor neuron disease (MND) were included. Diagnosis was established based on clinical criteria and supported by neurophysiological studies according to the revised El Escorial criteria for the diagnosis of amyotrophic lateral sclerosis (ALS). All patients underwent detailed clinical evaluation, including history, neurological examination, and assessment of disease onset, distribution of weakness, progression pattern, and associated bulbar or respiratory involvement. Electromyography (EMG) was performed to confirm lower motor neuron involvement and to exclude other causes of neuropathy or myopathy. Nerve conduction studies, routine hematological and biochemical investigations, and relevant imaging (MRI brain and spine) were performed to exclude structural lesions. Patients were followed up at regular intervals every six months, and clinical progression was documented using the ALS Functional Rating Scale-Revised (ALSFRS-R). Survival duration, site of onset, and presence of bulbar involvement were analyzed for prognostic significance. Data were compiled and statistically analyzed using descriptive statistics, chi-square test, and Kaplan–Meier survival analysis where applicable.

A total of 30 patients diagnosed with motor neuron disease (MND) were included in the study. The age of patients ranged from 28 to 74 years, with a mean age of 52.6 ± 11.4 years. There was a marked male predominance with a male-to-female ratio of 2.3:1. The mean duration of symptoms at presentation was 12.8 months (range 3–36 months) . Clinical Presentation The limb-onset type was the most common presentation, seen in 22 patients (73.3%), while bulbar-onset disease was observed in 8 patients (26.7%). The initial symptoms were asymmetric limb weakness in 18 patients (60%), dysarthria in 6 patients (20%), and dysphagia in 4 patients (13.3%). Fasciculations were noted in 20 patients (66.7%), muscle wasting in 24 patients (80%), and spasticity in 12 patients (40%). Neurophysiological Findings Electromyography (EMG) demonstrated evidence of chronic denervation and reinnervation in all cases. Upper motor neuron signs were present in 24 patients (80%), confirming the diagnosis of amyotrophic lateral sclerosis (ALS), while 6 patients (20%) had lower motor neuron signs only, consistent with progressive muscular atrophy (PMA). Disease Course and Survival During the follow-up period, 18 patients (60%) succumbed to the illness, 6 (20%) were alive with slow progression, and 6 (20%) were lost to follow-up. The mean survival duration from symptom onset was 38.2 ± 14.6 months. Patients with bulbar onset had a significantly shorter mean survival (26.4 ± 8.3 months) compared to limb onset (42.6 ± 12.1 months) (p < 0.05). Associated Features Cognitive impairment suggestive of frontotemporal dysfunction was observed in 3 patients (10%), and respiratory involvement in the form of dyspnea or nocturnal hypoventilation was noted in 5 patients (16.7%). No family history of similar illness was recorded.

In this ten-year prospective study of 30 cases of motor neuron disease (MND), the mean age at onset was 52.6 years, with a male predominance (2.3:1). These findings are consistent with global epidemiological trends that show higher incidence in middle-aged males [5,6]. The predominance of limb-onset disease (73.3%) and the relatively smaller proportion of bulbar-onset cases (26.7%) also align with previous reports [7,8]. The mean survival duration in our cohort was 38.2 months, similar to previous studies reporting a median survival of 30–50 months from symptom onset [9]. As observed in other cohorts, patients with bulbar onset had significantly shorter survival compared to limb onset, emphasizing the prognostic importance of disease phenotype [10,11]. Electrophysiological confirmation of widespread denervation was present in all patients, confirming the diagnostic value of EMG in distinguishing MND from other neuropathies or myopathies [12]. Approximately 20% of our cases met the clinical criteria for progressive muscular atrophy (PMA), which is comparable to reports indicating 10–20% prevalence among MND subtypes [13]. Although PMA generally shows slower progression, some patients later develop upper motor neuron signs, suggesting a spectrum of disease rather than distinct entities [14]. The presence of cognitive impairment in 10% of our patients supports growing evidence linking MND with frontotemporal cognitive dysfunction [15]. This overlap highlights the broader neurodegenerative nature of the disorder beyond pure motor involvement. The mean survival of 38 months in this Indian cohort is comparable to international data but slightly higher than earlier Indian series, such as that by Nalini et al. [3], possibly due to better supportive care and earlier diagnosis. The absence of familial cases and the rarity of respiratory involvement at presentation in our study align with findings from other Asian populations [16]. Long-term observational studies such as ours remain essential to understanding regional variations in MND progression and outcomes. Although limited by small sample size and loss to follow-up, our findings reinforce the clinical heterogeneity and prognostic diversity of MND and underline the importance of multidisciplinary management to improve survival and quality of life.

This ten-year observational study highlights the clinical diversity and variable progression of motor neuron disease (MND) in an Indian cohort. The predominance of limb-onset disease and male preponderance are consistent with international reports. Mean survival duration was approximately 38 months, with significantly shorter survival in bulbar-onset cases, reaffirming the prognostic influence of disease phenotype. Electrophysiological studies confirmed widespread denervation in all cases, underscoring the diagnostic importance of EMG in differentiating MND from other neuromuscular disorders. The presence of cognitive impairment in a subset of patients supports the concept of MND as part of a broader neurodegenerative spectrum. Although the sample size was modest, this long-term follow-up contributes valuable regional data, reflecting patterns comparable to global trends while emphasizing the need for early diagnosis, multidisciplinary management, and palliative support to improve quality of life and survival in patients with MND. Future research with larger, multicentric cohorts and incorporation of genetic and neuroimaging biomarkers is essential to better understand disease mechanisms and therapeutic targets [17].

1.Van den Berg-Vos RM, Visser J, Kalmijn S, et al. A long-term prospective study of the natural course of sporadic adult-onset lower motor neuron syndromes. Arch Neurol. 2009;66(6):751–757. doi:10.1001/archneurol.2009.91. 2.Arora RD. Motor neuron disease. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560774/ 3.Nalini A, Thennarasu K, Yamini BK, et al. Madras motor neuron disease (MMND): clinical description and survival pattern of 116 patients from Southern India seen over 36 years (1971–2007). J Neurol Sci. 2008;275(1–2):1–7. doi:10.1016/j.jns.2008.07.015. 4. Logroscino G, Traynor BJ, Hardiman O, et al. Incidence of amyotrophic lateral sclerosis in Europe. J Neurol Neurosurg Psychiatry. 2010;81(4):385–390. doi:10.1136/jnnp.2009.199535. 5.Zoccolella S, Beghi E, Palagano G, et al. Predictors of long survival in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2008;79(1):33–37. doi:10.1136/jnnp.2007.118016. 6.Park J, Lee J, Lee J, et al. The global burden of motor neuron disease: an analysis of the Global Burden of Disease Study 2019. Front Neurol. 2022;13:864339. doi:10.3389/fneur.2022.864339. 7.Chiò A, Logroscino G, Traynor BJ, et al. Global epidemiology of amyotrophic lateral sclerosis: a systematic review of the published literature. Neuroepidemiology. 2013;41(2):118–130. doi:10.1159/000351153. 8.Hardiman O, Al-Chalabi A, Chio A, et al. Amyotrophic lateral sclerosis. Nat Rev Dis Primers. 2017;3:17071. doi:10.1038/nrdp.2017.71. 9.Marin B, Couratier P, Arcuti S, et al. Age-specific ALS incidence and survival: a population-based study in France. Neuroepidemiology. 2018;51(3–4):117–128. doi:10.1159/000493386. 10.Turner MR, Parton MJ, Leigh PN, Talbot K. Prolonged survival in motor neuron disease: a descriptive study of the King's database 1990–2002. J Neurol Neurosurg Psychiatry. 2003;74(7):995–997. doi:10.1136/jnnp.74.7.995. 11.Gordon PH, Cheng B, Katz IB, et al. The natural history of primary lateral sclerosis. Neurology. 2006;66(5):647–653. doi:10.1212/01.wnl.0000201189.94701.72. 12.De Carvalho M, Dengler R, Eisen A, et al. Electrodiagnostic criteria for diagnosis of ALS. Clin Neurophysiol. 2008;119(3):497–503. doi:10.1016/j.clinph.2007.09.143. 13.Van den Berg-Vos RM, Franssen H, Wokke JHJ, et al. Multifocal motor neuropathy: long-term follow-up of 50 patients. Brain. 2002;125(9):1875–1886. doi:10.1093/brain/awf195. 14.Visser J, de Jong JM, de Visser M. The history of progressive muscular atrophy: syndrome or disease? Neurology. 2008;70(8):723–727. doi:10.1212/01.wnl.0000280578.28763.a4. 15.Phukan J, Elamin M, Bede P, et al. The syndrome of cognitive impairment in amyotrophic lateral sclerosis: a population-based study. J Neurol Neurosurg Psychiatry. 2012;83(1):102–108. doi:10.1136/jnnp-2011-300188. 16.Xu L, Liu T, Liu L, et al. Epidemiology and clinical features of amyotrophic lateral sclerosis in China: a nationwide observational study. Lancet Reg Health West Pac. 2022;18:100320. doi:10.1016/j.lanwpc.2021.100320. 17.Al-Chalabi A, Hardiman O, Kiernan MC, Chiò A, Rix-Brooks B, van den Berg LH. Amyotrophic lateral sclerosis: moving towards a new classification system. Lancet Neurol. 2016;15(11):1182–1194. doi:10.1016/S1474-4422(16)30199-5.