Refined Analysis of Chronic White Matter Changes after Traumatic Brain Injury and Repeated Sports-Related Concussions: Of Use in Targeted Rehabilitative Approaches?

Traumatic brain injury (TBI) or repeated sport-related concussions (rSRC) may lead to long-term memory impairment. Diffusion tensor imaging (DTI) is helpful to reveal global white matter damage but may underestimate focal abnormalities. We investigated the distribution of post-injury regional white matter changes after TBI and rSRC. Six patients with moderate/severe TBI, and 12 athletes with rSRC were included ≥6 months post-injury, and 10 (age-matched) healthy controls (HC) were analyzed. The Repeatable Battery for the Assessment of Neuropsychological Status was performed at the time of DTI. Major white matter pathways were tracked using q-space diffeomorphic reconstruction and analyzed for global and regional changes with a controlled false discovery rate. TBI patients displayed multiple classic white matter injuries compared with HC (p < 0.01). At the regional white matter analysis, the left frontal aslant tract, anterior thalamic radiation, and the genu of the corpus callosum displayed focal changes in both groups compared with HC but with different trends. Both TBI and rSRC displayed worse memory performance compared with HC (p < 0.05). While global analysis of DTI-based parameters did not reveal common abnormalities in TBI and rSRC, abnormalities to the fronto-thalamic network were observed in both groups using regional analysis of the white matter pathways. These results may be valuable to tailor individualized rehabilitative approaches for post-injury cognitive impairment in both TBI and rSRC patients.

Leukoencephalopathy with brain calcifications and cysts (Labrune syndrome) case report: diagnosis and management of a rare neurological disease

Background Leukoencephalopathy with brain calcifications and cysts (LCC; also known as Labrune syndrome) is a rare genetic microangiopathy caused by biallelic mutations in SNORD118. The mechanisms by which loss-of-function mutations in SNORD118 lead to the phenotype of leukoencephalopathy, calcifications and intracranial cysts is unknown. Case presentation We present the histopathology of a 36-year-old woman with ataxia and neuroimaging findings of diffuse white matter abnormalities, cerebral calcifications, and parenchymal cysts, in whom the diagnosis of LCC was confirmed with genetic testing. Biopsy of frontal white matter revealed microangiopathy with small vessel occlusion and sclerosis associated with axonal loss within the white matter. Conclusions These findings support that the white matter changes seen in LCC arise as a consequence of ischemia rather than demyelination.

NI-19 A case of Leber’s hereditary optic neuropathy with diffuse white matter changes mimicking gliomatosis cerebri

BACKGROUND: Leber’s hereditary optic neuropathy (LHON) is a mitochondrial disease characterized by bilateral severe subacute central vision loss and a mutation in the mitochondrial DNA (mtDNA). The cranial magnetic resonance imaging (MRI) of LHON patients varies from subtle to multiple white matter changes. However, they rarely present with diffuse infiltrative white matter changes. CASE REPORT: We report a case with diffuse white matter changes mimicking gliomatosis cerebri (GC). The histological findings included only mild glial hyperplasia without immunohistochemical positivity supporting the diagnosis of glial tumors. Analysis of mtDNA obtained from the blood and brain tissue revealed mutation of m.11778G&gt;A in the NADH dehydrogenase 4 gene, which confirmed the case as LHON. Immunohistochemistry of the brain tissue revealed 8-hydroxy-2’-deoxyguanosine positivity, suggesting the presence of oxidative stress. CONCLUSION: LHON is extremely difficult to diagnose unless we suspect or know the disease. The present case brings attention not only to LHON but other mtDNA mutated diseases that need to be considered with diffuse white matter changes or GC.

Cilostazol Versus Aspirin on White Matter Changes in Cerebral Small Vessel Disease: A Randomized Controlled Trial

Background and Purpose: Cerebral small vessel disease is characterized by progressive cerebral white matter changes (WMCs). This study aimed to compare the effects of cilostazol and aspirin on changes in WMC volume in patients with cerebral small vessel disease. Methods: In a multicenter, double-blind, randomized controlled trial, participants with moderate or severe WMCs and at least one lacunar infarction detected on brain magnetic resonance imaging were randomly assigned to the cilostazol and aspirin groups in a 1:1 ratio. Cilostazol slow release (200 mg) or aspirin (100 mg) capsules were administered once daily for 2 years. The primary outcome was the change in WMC volume on magnetic resonance images from baseline to 2 years. Secondary imaging outcomes include changes in the number of lacunes or cerebral microbleeds, fractional anisotropy, and mean diffusivity on diffusion tensor images, and brain atrophy. Secondary clinical outcomes include all ischemic strokes, all ischemic vascular events, and changes in cognition, motor function, mood, urinary symptoms, and disability. Results: Between July 2013 and August 2016, 256 participants were randomly assigned to the cilostazol (n=127) and aspirin (n=129) groups. Over 2 years, the percentage of WMC volume to total WM volume and the percentage of WMC volume to intracranial volume increased in both groups, but neither analysis showed significant differences between the groups. The peak height of the mean diffusivity histogram in normal-appearing WMs was significantly reduced in the aspirin group compared with the cilostazol group. Cilostazol significantly reduced the risk of ischemic vascular event compared with aspirin (0.5 versus 4.5 cases per 100 person-years; hazard ratio, 0.11 [95% CI, 0.02–0.89]). Conclusions: There was no significant difference between the effects of cilostazol and aspirin on WMC progression in patients with cerebral small vessel disease. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01932203.

White matter changes in focal to bilateral tonic-clonic seizures

Objective: A better understanding of the mechanistic underpinnings of focal to bilateral tonic-clonic seizures (FBTCS) would aid treatment decisions, and improve disease management for drug-refractory patients. We sought to examine the microstructural white matter differences in patients with FBTCS, compared to those with focal epilepsy without FBTCS, and control participants. Methods: We combined a superior tract segmentation model with track-weighted tensor metrics (TW-TM) in an advanced, automated image analysis and tract reconstruction pipeline. Univariate analysis of covariance (ANCOVA) tests were used to compare group differences in both whole-tract metrics and hemispheric tract metrics. Results: We identified a range of white matter regions that displayed significantly altered white matter in patients with and without FBTCS, compared to controls. Specifically, patients without FBTCS had significantly increased white matter disruption in the inferior fronto-occipital fascicle and the striato-occipital tract. In contrast, patients with FBTCS were more similar to healthy controls in most regions, except for distinct alterations in the inferior cerebellar region compared to the non-FBTCS group and controls. Significance: This study exploited track-weighted tensor metrics (TW-TM) to investigate white matter changes in FBTCS. Our findings revealed marked alterations in a range of subcortical regions widely considered critical in the genesis of seizures. Our application of TW-TM in a new clinical dataset allowed the identification of specific tracts that may act as a predictive biomarker to distinguish patients who are likely to develop FBTCS.