Progressive Asymmetrical Limb Impairment and Cognitive Decline With Leukoencephalopathy

A 41-year-old man sought care for progressive left-sided impairment over many months consistent with progressive left hemiapraxia and left hemiparesis and cognitive decline. He also exhibited features of the alien limb phenomenon, with the left arm grabbing things involuntarily. He had no prior medical disorders and no family history of significant neurologic disorders. Initial evaluations with brain magnetic resonance imaging showed evidence of bilateral, asymmetrical, severe white matter abnormalities, right greater than left hemisphere. There was no gadolinium enhancement. Cervical and thoracic spine magnetic resonance imaging findings were normal. The magnetic resonance imaging white matter abnormalities progressed over serial imaging. Cerebrospinal fluid assessment was normal except for increased neuron-specific enolase value, without increased white blood cells, immunoglobulin G index, or unique cerebrospinal fluid oligoclonal bands. A brain biopsy of the right hemispheric white matter showed marked axonal spheroids on hematoxylin and eosin staining, as well as on electron microscopy. A diagnosis of sporadic, adult-onset, diffuse leukoencephalopathy with axonal spheroids was made. There are no known treatments for diffuse leukoencephalopathy with axonal spheroids. Treatment is symptomatic only, directed by physical medicine and rehabilitation experts and cognitive experts. Continued rapid worsening of the patient’s ambulatory dysfunction over months required increasing use of gait aids, including a cane and wheelchair. He had development of neurogenic bladder dysfunction and pseudobulbar-associated emotional incontinence. His condition progressed leading to death 29 months after onset of his neurologic dysfunction. This case patient had common features of sporadic, adult-onset, diffuse leukoencephalopathy with axonal spheroids, with progressive neurologic degeneration typically over months to a few years, often with substantial asymmetry in presentation.

White Matter Abnormalities in Patients With Typhoon-Related Posttraumatic Stress Disorder

Patients with posttraumatic stress disorder (PTSD) might have white matter abnormalities. However, less is known about white matter changes after exposing a specific traumatic event. The purpose of this study was to explore the abnormalities of diffusion in cerebral white matter and its relationship with the clinical symptoms in patients with PTSD by using diffusion tensor imaging (DTI). Diffusion-weighted imaging of the cerebrum was performed in typhoon survivors with (n = 27) and without PTSD (n = 33) and healthy controls (HCs) (n = 30). Differences in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were calculated among groups using voxel-based analysis of the DTI data. Correlations between diffusion indices and clinical symptoms in patients with PTSD were also assessed. Both patients with PTSD and trauma-exposed control (TEC) group showed increased FA in the anterior limb of the internal capsule, forceps of the corpus callosum, and corona radiata relative to the HC group. Additionally, there was a negative correlation between FA values in the white matter and the clinical symptoms. Trauma exposure may result in disruption of cerebral white matter in individuals with or without PTSD, particularly in the frontal fibers. Aberrant white matter alterations may be associated with the severity of PTSD symptoms.

Infantile-Onset Charcot–Marie–Tooth Disease With Pyramidal Features and White Matter Abnormalities Due to a De novo MORC2 Gene Variant: A Case Report and Brief Review of the Literature

Background: Charcot–Marie–Tooth (CMT) is the most frequent group of inherited neuropathies and includes several heterogeneous phenotypes. Over 80 causative genes have been described so far. Variants in the microrchidia family CW-type zinc finger 2 (MORC2) gene have been described in several axonal polyneuropathy (CMT2) patients with childhood or adult onset. Occasionally more complex phenotypes with delayed milestones, severe hypotonia, intellectual disability, dystonic postures, pyramidal signs, and neuroimaging abnormalities have been reported.Case Presentation: We report on a patient with a de novo MORC2 gene variant (c.1181A>G p.Tyr394Cys) with a history of developmental delay, axial hypotonia, progressive gait disorder with dystonic features, and intentional tremor. At the age of 8 years, he showed bilateral pyramidal signs (clonus, increased tendon reflexes, and Babinski sign) and bilateral pes cavus. The first neuroimaging performed at the age of 3 years demonstrated white matter abnormalities in the posterior periventricular zone, in the frontal lobes bilaterally and at the midbrain, stable during childhood and adolescence. Nerve conduction studies (NCS) were negative until the age of 15 years, when a sensory axonal neuropathy appeared. The association between pyramidal signs and neuropathy due to the MORC2 gene variant is increasingly being highlighted, although a neuroradiological correlate is evident only in about half of the cases. Longitudinal nerve conduction velocity (NCV) are helpful to identify late-onset features and provide useful information for diagnosis in patients with rare neurogenetic disorders.Conclusions: Characterization of complex neurological disorders is important to delineate the expanding phenotypic spectrum of MORC2-related disease, to confirm if possible the pathogenicity of the variants and to deepen the genotype–phenotype correlation.

Brain White Matter Structure and Amyloid Deposition in Black and White Older Adults: The ARIC‐PET Study

Background White matter abnormalities are a common feature of aging and Alzheimer disease, and tend to be more severe among Black individuals. However, the extent to which white matter abnormalities relate to amyloid deposition, a marker of Alzheimer pathology, remains unclear. This cross‐sectional study examined the association of white matter abnormalities with cortical amyloid in a community sample of older adults without dementia and examined the moderating effect of race. Methods and Results Participants from the ARIC‐PET (Atherosclerosis Risk in Communities‐Positron Emission Tomography) study underwent brain magnetic resonance imaging, which quantified white matter hyperintensity volume and microstructural integrity using diffusion tensor imaging. Participants received florbetapir positron emission tomography imaging to measure brain amyloid. Associations between measures of white matter structure and elevated amyloid status were examined using multivariable logistic regression. Among 322 participants (43% Black), each SD increase in white matter hyperintensity volume was associated with a greater odds of elevated amyloid (odds ratio [OR], 1.37; 95% CI, 1.03–1.83) after adjusting for demographic and cardiovascular risk factors. In race‐stratified analyses, a greater white matter hyperintensity volume was more strongly associated with elevated amyloid among Black participants (OR, 2.00; 95% CI, 1.15–3.50), compared with White participants (OR, 1.29; 95% CI, 0.89–1.89). However, the race interaction was not statistically significant ( P interaction=0.09). We found no association between white matter microstructure and elevated amyloid. Conclusions The results suggest a modest positive relationship between white matter hyperintensity and elevated amyloid in older adults without dementia. Although the results indicate that this association is nonsignificantly stronger among Black participants, these findings will need to be confirmed or refuted using larger multiracial cohorts.

Subclinical Atherosclerosis, Vascular Risk Factors, and White Matter Alterations in Diffusion Tensor Imaging Findings of Older Adults With Cardiometabolic Diseases

White matter abnormalities may reflect cerebral microvessel disease. Diffusion tensor imaging (DTI) can help detect early changes in white matter integrity in each tract. However, studies investigating the relationship between subclinical atherosclerosis markers and white matter alterations in DTI findings are limited. This study aimed to examine associations between cardiovascular risk factors and indices of subclinical atherosclerosis—ankle brachial index (ABI), brachial-ankle pulse wave velocity (baPWV), and carotid artery intima-media thickness (IMT)—and altered white matter integrity in older patients. A total of 224 patients (aged ≥65 years) with cardiometabolic disease who underwent magnetic resonance imaging (MRI) and either plethysmography or cervical ultrasound at the start of the 3-year observational study period were included in this study. We measured fractional anisotropy (FA) and mean diffusivity (MD), which are indices of white matter integrity in seven white matter tracts. In a univariate analysis, lower ABI and higher baPWV values were associated with FA or MD abnormalities in several tracts, whereas IMT was scarcely associated with such change. In addition, high blood pressure and glycoalbumin/glycohemoglobin ratio (GA/HbA1c) and low body mass index (BMI) and triglyceride (TG) levels were associated with FA or MD abnormalities. In a multivariate analysis adjusted for age, sex, BMI, diastolic blood pressure, TG, and GA/HbA1c, the associations between ABI and FA or MD remained in all of either side of the following tracts: anterior thalamic radiation, forceps minor, inferior frontooccipital fasciculus (p < 0.001 for all) and superior longitudinal fasciculus (SLF; p < 0.05), whereas most of those between baPWV and FA or MD disappeared except for SLF (p < 0.05). These results indicate that low ABI could be an indicator of white matter abnormalities.