White matter of the central nervous system (CNS) forms an extensive network of myelinated and unmyelinated nerve fibers that enables rapid communication between cortical and subcortical regions. It constitutes  nearly  half  of  total brain  volume  and  is  essential for  cognitive, sensory, motor, and behavioral functions[1]. White matter disorders, commonly referred to as Leukoencephalopathies, comprise a broad spectrum of diseases characterized by abnormalities in myelin formation,  maintenance, or  its  destruction. Since  myelin is critical  for efficient saltatory conduction and axonal protection, damage to  white matter can result in  significant neurological dysfunction.

Myelin is produced by oligodendrocytes and consists of water, lipids, cholesterol, phospholipids, galactolipids, and proteins[2]. Its structural integrity depends on  the coordinated interaction of

oligodendrocytes, axons, astrocytes, microglia, and precursor cells. Disruption  at any point in this complex system due to genetic, inflammatory, metabolic, vascular, infectious, toxic, or traumatic causes may lead to white matter injury.

White matter disorders may broadly be classified into demyelinating, dysmyelinating, and hypomyelinating disorders. Demyelinating disorders involve destruction of previously normal myelin and include multiple sclerosis (MS), acute disseminated encephalomyelitis (ADEM), neuromyelitis optica spectrum disorders (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease[3]. Dysmyelinating disorders are caused by inherited defects in myelin metabolism, resulting in structurally abnormal myelin. Classical leukodystrophies such as metachromatic leukodystrophy, adrenoleukodystrophy, Krabbe disease, and Canavan disease fall within this group[4–7]. Hypomyelinating disorders are characterized by deficient formation of otherwise  normal myelin  and  include  Pelizaeus–Merzbacher disease,  4H  leukodystrophy, Salla disease, and hypomyelination with atrophy of the basal ganglia and cerebellum.

White matter  lesions  (WMLs) can  arise  from  both  vascular  and  non-vascular  causes. Vascular causes commonly include chronic hypoperfusion, cerebral small vessel disease, vasculitis, atherosclerosis, migraine-related vascular changes, cerebral amyloid angiopathy, and Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL)[8]. These lesions typically appear as periventricular or deep white matter hyperintensities on magnetic resonance imaging (MRI). Risk factors such as hypertension, diabetes mellitus, dyslipidemia, smoking, hyperhomocysteinemia, systemic inflammation, and aging significantly contribute to lesion burden [8].Non-vascular causes include inflammatory demyelination, metabolic and toxic encephalopathies, infectious conditions such as HIV- associated leukoencephalopathy and progressive multifocal leukoencephalopathy, traumatic diffuse axonal injury, autoimmune disorders, neoplastic infiltration, and inherited leukodystrophies[4,9]. Depending on the underlying pathology, these disorders may produce focal, multifocal, symmetric, or  confluent  white  matter  abnormalities.Clinical  manifestations  of white matter disorders are highly variable and depend on lesion location, burden, etiology, and age of onset. Mild punctate lesions may remain asymptomatic, especially in older individuals, whereas extensive WMLs are associated with cognitive decline, executive dysfunction, gait disturbances, urinary symptoms, depression, dementia, and disability[9–11]. Several studies have shown that WMLs are independent predictors of stroke, dementia, disability, and mortality[10–12]. In demyelinating disorders such as MS,  symptoms commonly include  sensory disturbances,  visual loss, motor weakness, bladder dysfunction, fatigue, and cognitive impairment[3].MRI has revolutionized the evaluation of white matter disorders because of its superior soft tissue contrast, multiplanar capability, and high sensitivity for detecting microstructural abnormalities[13]. T1-weighted images provide information regarding myelin integrity and cerebral atrophy, while T2-weighted and fluid-attenuated inversion recovery (FLAIR) sequences highlight edema,  gliosis,  and  demyelination.  Diffusion-weighted  imaging  (DWI)  is  particularly useful in detecting acute ischemia and cytotoxic edema, whereas diffusion tensor imaging (DTI) helps evaluate tract integrity. Susceptibility-weighted imaging (SWI) is useful for detecting microhemorrhages and mineralization, and contrast-enhanced MRI helps identify active inflammation.Certain MRI patterns are highly suggestive of specific diseases. Dawson’s fingers are characteristic of MS, the tigroid pattern is often  seen in  metachromatic leukodystrophy, and confluent  deep  white  matter involvement is  commonly associated  with CADASIL[13,14]. MRI  is also useful for differentiating acute from chronic lesions, monitoring disease progression, assessing response to treatment, and guiding further biochemical or genetic investigations. Despite advances in MRI, interpretation of white matter abnormalities remains challenging because of the significant overlap in imaging features among different diseases. A structured MRI-based approach focusing on lesion distribution, symmetry, enhancement, diffusion restriction, and associated gray matter or spinal cord involvement can improve diagnostic accuracy[14]. Therefore, evaluation of MRI findings is essential for early diagnosis, timely treatment, and improved patient outcomes in white matter disorders.

This hospital-based cross-sectional observational study was conducted in the Department of Radiodiagnosis at Mahatma Gandhi Medical College and Hospital with the objective of evaluating the diagnostic role of magnetic resonance imaging (MRI) in clinically suspected cases

of white matter disorders.The study was carried out over a period from April 2024 to September 2025. All clinically suspected patients of white matter diseases referred from the Departments of Medicine  and  Neurology, including  both  outpatient  and  inpatient services, for MRI evaluation during the study period were screened for eligibility.All consecutive patients fulfilling the inclusion criteria were enrolled in the study. Since this was an observational diagnostic study, no prior fixed  sample  size  calculation  was  performed,  and  the  sample  size  was  determined  by  the number  of eligible  patients presenting  during the  study  period.Prior approval  for  the  study  was obtained        from the Institutional         Ethics     Committee              before commencement       of           data        collection.

Written  informed consent was  obtained from  all patients or their legally authorized  guardians after explaining the purpose of the study, MRI procedure, and the use of contrast media wherever required.Patients  of all  age  groups  with  clinically  suspected  white  matter  disorders referred  for MRI brain examination were included in the study.

Patients who refused consent, had contraindications to MRI such as cardiac pacemakers, intracranial aneurysm clips, cochlear implants, or metallic foreign bodies, had severe claustrophobia, or had a known history of severe hypersensitivity to contrast media were excluded from the study.MRI examinations were performed  using either 1.5 Tesla or 3 Tesla MRI scanners available in the Department of Radiodiagnosis. All patients were examined in the supine position using a standard head coil.The routine MRI protocol included axial, sagittal, and coronal sequences comprising T1-weighted imaging, T2-weighted imaging, fluid-attenuated inversion recovery (FLAIR), diffusion-weighted imaging (DWI), and post-contrast T1-weighted imaging wherever indicated. Contrast-enhanced MRI was selectively performed in patients with suspected inflammatory,  infective,  neoplastic,  or  active  demyelinating  lesions.  Prior  to  contrast administration, renal  function  status and  history  of allergy  to  contrast  agents  were  assessed.For each patient, demographic and clinical details were recorded in a structured proforma. Demographic variables included age, sex, and occupation. Clinical presentation was documented in  detail  and included  symptoms  such  as  seizures,  aphasia,  dementia, unilateral  visual  blurring, sensory disturbances, motor weakness, urinary incontinence, speech and swallowing difficulties, numbness, tingling sensations, and cognitive dysfunction.Relevant past medical histor y and vascular risk factors were also documented, including hypertension, diabetes mellitus, hyperlipidemia, hyperhomocysteinemia, and elevated C-reactive protein levels.All MRI scans were  systematically  evaluated  with  emphasis  on  lesion  location, morphology, distribution,  and signal characteristics. Lesion location was categorized as periventricular, deep white matter, subcortical, or infratentorial. Lesion distribution was assessed as focal or diffuse and symmetric or asymmetric. Signal characteristics on T1-weighted, T2-weighted, FLAIR, and DWI sequences were analyzed. The presence of diffusion restriction, contrast enhancement, gray matter involvement, mass effect, and cerebral atrophy was also noted.White matter lesions were graded using the Fazekas scale for periventricular and deep white matter involvement wherever applicable. MRI findings were interpreted in correlation with the clinical presentation to arrive at the most likely diagnosis.All MRI images were independently reviewed by experienced radiologists to reduce observer bias and improve diagnostic accuracy.

Statistical analysis was performed using SPSS version 25.. Categorical variables were expressed as frequency and percentage, while continuous variables were expressed as mean±standard deviation or median with  interquartile  range wherever appropriate. Chi-square  test or Fisher’s exact test was  used for comparison of categorical variables. A p-value of less than  0.05 was considered statistically significant.

A total of 50 patients with clinically suspected white matter disorders were included in the study.The  age  distribution  of the  study  population  showed a  predominance  of middle-aged and elderly  individuals.  The  highest proportion of  patients  belonged  to  the 41–60  years  age  group (36.0%), followed by patients aged more than 60 years (24.0%). The mean age of the study population was 46.8±17.2 years, with  a median  age of  48 years  (IQR: 32–62 years). Males constituted 56.0% of the study population, while females accounted for 44.0%, indicating a slight male predominance (Table 1, Figure 1).

Table 1. Demographic Characteristics of the Study Population (n = 50)

 Figure 1. Patient Distribution by Age Group and Gender

Cognitive impairment or dementia was the most common presenting symptom, observed in 36.0% of patients, followed by motor weakness (32.0%) and seizures (28.0%). Sensory disturbances and gait imbalance were present in nearly one-fourth of patients, while visual disturbances and urinary incontinence  were less  common.  Hypertension  was the  most  common associated clinical risk factor, present in 48.0% of patients, followed by diabetes mellitus (36.0%) and hyperlipidemia (32.0%) (Table 2, Figure 2).

 Table 2. Clinical Presentation and Risk Factors in the Study Population (n = 50)

Figure 2. Clinical Presentation and Risk Factors in the Study Population (n = 50)

Vascular etiology, predominantly small vessel ischemic disease, was the most common cause of white matter lesions, accounting for 44.0% of cases. Demyelinating disorders, including multiple sclerosis  and  acute disseminated encephalomyelitis, formed  the second  largest group  (32.0%). Infectious or inflammatory causes accounted for 12.0% of cases, while metabolic, toxic, and genetic causes together contributed  to  12.0% of cases. Small vessel ischemic disease was the most frequent final MRI diagnosis  (44.0%), followed by multiple sclerosis (28.0%) (Table  3, Figure 3).

Table 3. Etiological Classification and Final MRI Diagnosis of White Matter Disorders (n = 50)

Figure 3. Etiology of White Matter Pathologies

On  MRI,  all patients  demonstrated  hyperintense  lesions  on  T2-weighted  images, while FLAIR hyperintensity was observed in 96.0% of patients. T1 -weighted hypointense lesions were present in 76.0%, restricted diffusion in 28.0%, and post-contrast enhancement in 24.0% of cases. Periventricular  white  matter involvement  was the  most  common lesion location,  seen  in 60.0%

of patients, followed by deep white matter involvement (52.0%) and subcortical lesions (40.0%). Corpus callosum involvement was noted in 24.0% of patients and brainstem or cerebellar involvement in 16.0%. Confluent lesions were the most common lesion pattern, observed in 40.0%  of  cases,  and  asymmetric  involvement was more  common  than  symmetric  involvement (60.0% vs. 40.0%). According to Fazekas grading, Grade 2 lesions were the most common, seen in 40.0% of patients (Table 4).

Table 4. MRI Characteristics and Lesion Distribution in White Matter Disorders (n = 50)

 A statistically significant association was observed between age group and etiology of white matter lesions (p =  0.002).  Vascular lesions  were  more  common in  patients aged  more than  40 years, whereas demyelinating disorders predominated in younger patients  aged 40  years or less. Periventricular lesions were significantly more common in vascular etiologies compared to non - vascular causes (81.8% vs. 42.9%, p = 0.01). In contrast, corpus callosum involvement, contrast enhancement, and restricted diffusion were significantly more frequent in non-vascular disorders, particularly demyelinating diseases. MRI diagnosis was concordant with the final clinical diagnosis in 80.0% of patients. MRI demonstrated excellent sensitivity (95.5%) and high diagnostic accuracy (90.0%) for detecting white matter disorders, although specificity was moderate (50.0%) (Table 5, Figure 4).

Table 5. Association of MRI Findings with Etiology and Diagnostic Performance of MRI

Figure 4. Diagnostic Performance of MRI

Case of ISCHEMIC DEMYELINATION

 Axial T2 and Flair images showing confluent peri ventricular white matter hyperintensities

Case of MULTIPLE SCLEROSIS

Axial T2 and Flair images showing sub cortical and peri ventricular hyperintensities Sagittal T2 image of cervical spine showing patchy areas of white matter hyper intensities in cervical cord

Case of ADEM

Axial T2 and Flair images showing Confluent and patchy hyperintensities involving bilateral basal ganglia Left>Right

Case of METACHROMATIC LEUKODYSTROPHY

Axial T2 and Flair images showing confluent T2 hyperintensities adjoining the frontal and

occipital horns

In this hospital-based cross-sectional study involving 50 patients with clinically suspected white matter disorders, comprehensive MRI evaluation allowed detailed assessment of lesion characteristics, distribution, pattern, severity, and etiological classification, which were th en correlated  with  clinical  findings.  The  mean age  of the  study  population  was 46.8±17.2  years, with a median age of 48 years, and the highest proportion of patients belonged to the 41–60 years age  group (36.0%). This  predominance of middle-aged and  elderly  patients indicates that  white matter  disorders are  more  commonly identified in adulthood,  likely  due to  cumulative  vascular and degenerative changes[15,16]. These findings are consistent with Barkovich et al. (2000)[15], who reported that adult white matter disorders are predominantly acquired, and with Schiffmann et al. (2009)[14], emphasizing the relevance of MRI-based diagnostic algorithms in adult populations. Males constituted  56% of patients, indicating  a slight male predominance, which aligns with previous studies by Rana et al. (2018)[18] and Gowdar et al. (2015)[17], reporting54–58%  male  prevalence  in  similar cohorts.  This is contrasted  by  demyelinating  disorders  such as multiple sclerosis, which show female predominance[19,20]. The sex distribution in our study reflects  the  mixed  etiology,  with  vascular and  metabolic lesions being  more  frequent.Cognitive impairment was  the most common  presenting  symptom  (36.0%), followed  by motor weakness (32.0%) and seizures (28.0%), with sensory disturbances (24.0%), gait imbalance (22.0%), visual disturbances (20.0%), and urinary incontinence (14.0%). These findings suggest predominant involvement of cortical and long motor–sensory pathways. Similar symptom distribution was reported by Barkovich et al. (2000)[15], Sharma et al. (2025)[8], and Debette et al. (2010)[9], emphasizing the strong association between white matter hyperintensities and cognitive decline, gait disturbances, and seizures. Etiologically, vascular causes, mainly small vessel ischemic disease, accounted for 44.0% of cases, followed by demyelinating disorders (32.0%), infectious/inflammatory (12.0%), metabolic/toxic (8.0%), and genetic/leukodystrophy (4.0%) These results correspond with prior adult studies by Weidauer et al.  (2020)[16] and Sharma  et al. (2025)[8], highlighting  small  vessel ischemic  disease as the  leading  cause  of adult white  matter lesions. Demyelinating  disorders were  more  frequent in younger patients (≤40 years), reflecting an age-dependent etiological pattern consistent with Lakhkar et al. (2002)[19] and Rana et al. (2018)[18].MRI findings demonstrated universal T2 hyperintensity (100%), FLAIR hyperintensity in 96%, T1 hypointensity in 76%, restricted diffusion in 28%, and contrast enhancement in 24%(Table 2). Periventricular involvement was most common (60%), followed by deep white matter (52%), subcortical (40%), corpus callosum (24%), and brainstem/cerebellum  (16%). Vascular lesions were predominantly periventricular,  whereas non-vascular lesions showed higher  corpus callosum involvement, greater contrast enhancement, and diffusion restriction (Table 4), supporting prior observations by Schiffmann et al. (2009)[14], Lakhkar et al. (2002)[19], and Hesselink et al. (2006)[21].Pattern analysis showed that confluent lesions were most frequent (40%), with  asymmetric  involvement  in  60%  of  patients. Moderate  severity  (Fazekas  grade  2) was the most  common (40%), indicating  established but  not  end-stage pathology. These  results mirror reports by Weidauer et al. (2020) [16], Sharma  et al. (2025)[8], and Rana et al. (2018)[18], highlighting the association of lesion morphology with etiology and chronicity. MRI-based diagnosis demonstrated 80.0% concordance with the final clinical diagnosis, particularly high for small vessel ischemic disease (81.8%) and multiple sclerosis (78.6%) (Table 5). Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 95.5%, 50.0%, 93.3%, 60.0%, and 90.0%, respectively. These metrics are comparable with published data by Datar et al. (2018)[20], Barkovich et al. (2000)[15], and Malani et al. (2023)[22], underscoring MRI’s excellent sensitivity but moderate specificity due to overlapping imaging features across etiologies.

Overall findings of  this study  indicate  that MRI is  a highly  sensitive  and reliable  tool for the evaluation of white matter disorders. Vascular etiologies, particularly small vessel ischemic disease, were the most common, followed by demyelinating disorders. MRI effectively characterized lesion distribution, pattern, and severity, and showed strong concordance with clinical diagnosis. Age and vascular risk factors were significant determinants of lesion type and distribution.  Early  MRI assessment  facilitates accurate  diagnosis,  guides  management, and aids prognostication in patients with white matter abnormalities.

LIMITATIONS OF THE STUDY

1. The sample size was relatively small and derived from a single tertiary-care center, which may limit the generalizability of the findings.
2. The cross-sectional observational design precludes establishing causal relationships between risk factors and white matter lesions.
3. Long-term clinical outcomes and progression of lesions were not evaluated, limiting insight into the prognostic significance of the findings.

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