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Background and purpose The splenium of the corpus callosum is the most posterior part of the corpus callosum. Its embryological development, anatomy, vascularization, function, imaging of pathology, possible pathophysiological mechanisms by which pathology may develop and the clinical consequences are discussed. Methods A literature-based description is provided on development, anatomy and function. MR and CT images are used to demonstrate pathology. The majority of pathology, known to affect the splenium, and the clinical effects are described in three subsections: (A) limited to the splenium, with elaboration on pathophysiology of reversible splenial lesions, (B) pathology in the cerebral white matter extending into or deriving from the splenium, with special emphasis on tumors, and (C) splenial involvement in generalized conditions affecting the entire brain, with a hypothesis for pathophysiological mechanisms for the different diseases. Results The development of the splenium is preceded by the formation of the hippocampal commissure. It is bordered by the falx and the tentorium and is perfused by the anterior and posterior circulation. It contains different caliber axonal fibers and the most compact area of callosal glial cells. These findings may explain the affinity of specific forms of pathology for this region. The fibers interconnect the temporal and occipital regions of both hemispheres reciprocally and are important in language, visuospatial information transfer and behavior. Acquired pathology may lead to changes in consciousness. Conclusion The development, location, fiber composition and vascularization of the splenium make it vulnerable to specific pathological processes. It appears to play an important role in consciousness.

The corpus callosum has become a key area of interest for researchers in severe mental illness. Disruptions in fractional anisotropy in the callosum have been reported in schizophrenia and major depressive disorder. No change has been reported in oligodendrocyte density and overall size of the callosum in either illness, suggesting that gross morphology is unchanged, but subtler organisational disruption may exist within this structure. Using high-resolution oil immersion microscopy, we examined the cross-sectional area of the nerve fibre and the axonal myelin sheath; and using standard high-resolution light microscopy, we measured the density of myelinated axons. These measurements were made in the splenium of the corpus callosum. Measures were taken in the sagittal plane in the callosal splenium to contrast with the previous similar examination of the callosal genu. Cases of major depressive disorder had significantly decreased mean myelin cross-sectional area (p = 0.014) per axon in the splenium than in controls or schizophrenia groups. There was no significant change in the density of myelinated axons. The results suggest a clear decrease of myelin in the axons of the callosal splenium in MDD, although this type of neuropathological study is unable to clarify whether this is caused by changes during life or has a developmental origin. In contrast with increased myelin in the callosal genu, this result suggests a longitudinal change in callosal myelination in major depressive disorder not present in normal or schizophrenic brains.

Adult-onset neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder. Abnormally high signals of diffusion-weighted image (DWI) along the corticomedullary junction are a useful diagnostic indicator for patients with adult-onset NIID. However, the DWI abnormalities usually were observed in the late stage of disease; further study might be helpful to elucidate some clinical indicators regarding the early awareness of NIID. In this study, we summarized 9 patients with NIID from multiple centers. The mean age was 60.0 ± 6.2 years. The mean duration of disease was 4.4 ± 3.2 years. The most common symptoms included cognitive impairment, episodic encephalopathy, and bladder dysfunction. Among the 6 patients with bladder dysfunction, 3 patients had the symptom prior to the development of other neurological symptoms; 5 patients needed permanent cystostomy. Isolated high DWI signals on the splenium of corpus callosum were observed in 2 patients at the early stage. The characteristic intranuclear inclusions in the skin were identified in all patients and confirmed by electron microscopy. Episodic encephalopathy or bladder dysfunction prior to other neurological symptoms were valuable diagnostic indicators for adult-onset NIID. High DWI signals on the splenium of corpus callosum might be an early indicator for the diagnosis of NIID. The immunostain of anti-ubiquitin or anti-p62 antibody was a convenient and sensitive biomarker for NIID with the background of typical phenotype with cognitive impairment and autonomic dysfunctions.

Aim of Review The presence of isolated, reversible lesions in the splenium of the corpus callosum (SCC) is essential to confirm the diagnosis of mild encephalitis/encephalopathy. The lesions usually heal within a month after the onset of neurological symptoms. Magnetic resonance imaging (MRI) has increasingly been used as a diagnostic tool, which has led to the publication of an increasing number of case reports. These have highlighted some inconsistencies about encephalitis/encephalopathy. First, the condition is not always mild and may be severe. Second, reversible lesions in the SCC have been identified in various diseases and conditions other than viral encephalitis/encephalopathy. Third, lesions in SCC are not always completely reversible. On this note, this review describes the specific clinical and radiological features of encephalitis/encephalopathy. Findings The reversible lesion in SCC is an MRI finding observable in a wide variety of diseases and conditions. Thus, it should be considered as a secondary change rather than a peculiar feature associated with mild encephalitis/encephalopathy. If reversible lesions are present in the SCC, the symptoms and prognosis are not necessarily favorable, with manifestations of encephalitis/encephalopathy varying from absent to severe. Neuroradiological features that appear as isolated high‐intensity signals on diffusion‐weighted images and a decreased apparent diffusion coefficient of the lesion might indicate a diagnosis of cytotoxic edema. Findings of previous studies suggest that cytokine‐mediated cytotoxic edema of the SCC may be an important pathophysiological manifestation of this condition. Conclusion The reversible lesions in the SCC found on MRI are not exclusive to encephalitis/encephalopathy but may be secondary to other disorders. The reversible lesion in the SCC is an MRI finding in a wide variety of diseases and conditions. Findings of previous studies suggest that cytokine‐mediated cytotoxic edema of the SCC may be an important pathophysiological manifestation of this condition. The reversible lesions in the SCC found on MRI might be secondary to several disorders.

Ideational slippage—characterized by incorrect word usage and strained logic during dialogue—is common in aging and, at greater frequency, is an indicator of pre-clinical cognitive decline. Performance-based assessment of ideational slippage may be useful in the study of cognitive aging and Alzheimer’s-disease-related pathology. In this preliminary study, we examine the association between corpus callosum volume and a performance-based assessment of ideational slippage in middle-aged and older adults (age 61–79 years). Ideational slippage was indexed from cognitive special scores using the Rorschach Inkblot Method (RIM), which are validated indices of deviant verbalization and logical inaccuracy (Sum6, WSum6). Among middle-aged and older adults, smaller splenium volume was associated with greater ideational slippage (ηp2 = 0.48), independent of processing speed and fluid intelligence. The observed negative associations are consistent with visuospatial perception and cognitive functions of the splenium. The effect was strongest with the splenium, and volumes of the genu and total white matter had small effects that were not statistically significant. Conclusions: Results are discussed with future application of RIM special scores for the assessment of pre-clinical cognitive decline and, based on observed effect sizes, power analyses are reported to inform future study planning.

Alzheimer disease (AD) and vascular dementia (VaD) together represent the majority of dementia cases. Since their neuropsychological profiles often overlap and white matter lesions are observed in elderly subjects including AD, differentiating between VaD and AD can be difficult. Characterization of these different forms of dementia would benefit by identification of quantitative imaging biomarkers specifically sensitive to AD or VaD. Parameters of microstructural abnormalities derived from diffusion tensor imaging (DTI) have been reported to be helpful in differentiating between dementias, but only few studies have used them to compare AD and VaD with a voxelwise approach. Therefore, in this study a whole brain statistical analysis was performed on DTI data of 93 subjects (31 AD, 27 VaD, and 35 healthy controls-HC) to identify specific white matter patterns of alteration in patients affected by VaD and AD with respect to HC. Parahippocampal tracts were found to be mainly affected in AD, while VaD showed more spread white matter damages associated with thalamic radiations involvement. The genu of the corpus callosum was predominantly affected in VaD, while the splenium was predominantly affected in AD revealing the existence of specific patterns of alteration useful in distinguishing between VaD and AD. Therefore, DTI parameters of these regions could be informative to understand the pathogenesis and support the etiological diagnosis of dementia. Further studies on larger cohorts of subjects, characterized for brain amyloidosis, will allow to confirm and to integrate the present findings and, furthermore, to elucidate the mechanisms of mixed dementia. These steps will be essential to translate these advances to clinical practice.

Limb apraxia is a higher-order motor disorder often occurring post-stroke, which affects skilled actions. It is assessed through tasks involving gesture production or pantomime, recognition, meaningless gesture imitation, complex figure drawing, single and multi-object use. A two-system model for the organisation of actions hypothesizes distinct pathways mediating praxis deficits via conceptual, ‘indirect’, and perceptual ‘direct’ routes to action. Traditional lesion- symptom mapping techniques have failed to identify these distinct routes. We assessed 29 left hemisphere stroke patients to investigate white matter disconnections on deficits of praxis tasks from the Birmingham Cognitive Screening. White matter disconnection maps derived from patients’ structural T1 lesions were created using a diffusion-weighted healthy participant dataset acquired from the human connectome project (HCP). Initial group-level regression analyses revealed significant disconnection between occipital lobes via the splenium of the corpus callosum and involvement of the inferior longitudinal fasciculus in meaningless gesture imitation deficits. There was a trend of left fornix disconnection in gesture production deficits. Further, voxel-wise Bayesian Crawford single-case analyses performed on two patients with the most severe meaningless gesture imitation and meaningful gesture production deficits, respectively, confirmed distinct posterior interhemispheric disconnection, for the former, and disconnections between temporal and frontal areas via the fornix, rostrum of the corpus callosum and anterior cingulum, for the latter. Our results suggest distinct pathways associated with perceptual and conceptual deficits akin to ‘direct’ and ‘indirect’ action routes, with some patients displaying both. Larger studies are needed to validate and elaborate on these findings, advancing our understanding of limb apraxia.

The splenium of the corpus callosum plays a pivotal role in interhemispheric communication and undergoes various changes with ageing. The present study aimed to elucidate the age-related variations in splenial fluid-attenuated inversion recovery (FLAIR) hyperintensity, providing insights into the normal ageing process of the brain and enhancing the clinical interpretation of magnetic resonance (MR) imaging. In the present retrospective cohort study, cerebral MR imaging of 1,176 patients was analysed following application of strict inclusion and exclusion criteria to isolate age and sex-related changes and other factors that can affect splenium hyperintensity. The present study focused on measuring the thickness (anteroposterior) of splenial FLAIR hyperintensity, with interobserver agreement assessed to ensure measurement reliability. Statistical analyses, including the Mann-Whitney U test for sex comparisons and the Kruskal-Wallis test for age group comparisons, were employed to investigate the effects of age, sex, radiation therapy and Fazekas score on splenial FLAIR hyperintensity. The present study demonstrated a significant increase in the presence of splenial FLAIR hyperintensity and thickness (P<0.001; P=0.006) with advancing age, particularly in individuals >57 years of age. No significant differences were observed between male and female participants, suggesting that these age-related changes were consistent across sex. Splenium hyperintensity thickness was significantly higher in the group that received radiation therapy and in the patient group with a Fazekas score of 3 (0.048, 0.018). Interobserver agreement was evaluated using the intraclass correlation coefficient (ICC) to assess measurement consistency (ICC=0.977; P<0.001). The present study provides crucial insights into the age-related dynamics of the splenium.