## 1 Introduction  
Multiple sclerosis (MS), a chronic inflammatory and neurodegenerative disorder of the central nervous system (CNS), is marked by demyelination, axonal loss, and heterogeneous clinical manifestations [1]. While magnetic resonance imaging (MRI) remains the gold standard for diagnosing and monitoring MS [2], its utility is constrained by high costs, limited accessibility, and an inability to capture dynamic, real-time metabolic changes. Near-infrared (NIR) spectroscopy, a non-invasive optical technique that provides insights into tissue composition, blood oxygenation, and metabolic processes, has emerged as a promising tool for probing tissue changes in neurological disorders in both cranial [3]) and extracranial sites [3, 4, 5]. Recent advances in NIR spectroscopy technology now enable high-resolution spectral analysis, possibly offering novel insights into systemic manifestations of MS, such as peripheral neuroinflammation, microvascular dysfunction, and secondary tissue-specific changes. In MS, disrupted blood-brain barrier integrity, altered cerebral perfusion, and mitochondrial dysfunction contribute to disease progression [6], yet these processes remain challenging to monitor longitudinally. NIR spectroscopy-derived reflectance spectra provide wavelength-dependent information about chromophores (e.g., oxy/deoxyhemoglobin, lipids, or water) and scatterers (e.g., myelin or cellular membranes) [7], potentially serving as biomarkers for demyelination, inflammation, or metabolic stress. Extracranial measurements--such as those from skeletal muscles--may further reveal systemic correlates of CNS pathology, including endothelial dysfunction, autonomic dysregulation, and fiber hypotrophy, which are increasingly recognized as contributors to MS disability. MS-associated central nervous system dysfunction precipitates secondary skeletal muscle oxidative distress and microvascular abnormalities through several interconnected mechanisms. CNS demyelination and axonal injury in MS disrupt neuromuscular transmission, leading to reduced neural activation of skeletal muscle. This results in muscle disuse, atrophy, and metabolic deconditioning, which in turn impairs mitochondrial function within muscle fibers, increasing the production of reactive oxygen species (ROS) and promoting oxidative stress [8, 9, 10]. Mitochondrial dysfunction in the CNS, a hallmark of MS, is associated with increased ROS generation and impaired energy metabolism, which can extend systemically and affect peripheral tissues, including skeletal muscle [11, 12, 13, 14]. Experimental models demonstrate that early in the disease, skeletal muscle exhibits mitochondrial degeneration and increased oxidative stress markers, with these changes intensifying as neurogenic atrophy progresses [9]. The resulting oxidative distress impairs muscle contractility and promotes further muscle fiber damage. Additionally, chronic inactivity and altered muscle metabolism in MS patients contribute to microvascular abnormalities, such as reduced capillary density and impaired perfusion, further exacerbating muscle hypoxia and oxidative injury [8, 10]. Systemic inflammation and metabolic dysfunction associated with neurodegeneration also play a role in promoting muscle oxidative stress and microvascular compromise [10]. Overall, CNS dysfunction in MS leads to impaired neuromuscular signaling, muscle disuse, mitochondrial dysfunction, and systemic inflammation, collectively driving secondary skeletal muscle oxidative distress and microvascular abnormalities [11, 14]. Despite preliminary applications of NIR spectroscopy in MS for assessing motor cortex activation and fatigue [15], no study has comprehensively analyzed reflectance spectra across both cranial and extracranial sites in tandem. The present dual approach could address critical knowledge gaps, such as whether peripheral changes mirror CNS pathology or how non-neural tissue-specific spectral signatures correlate with disability.