Severity of white matter hyperintensities: Lesion patterns, cognition, and microstructural changes.

White matter hyperintensity (WMH) is a common finding in aging population and considered to be a contributor to cognitive decline. Our study aimed to characterize the spatial patterns of WMH in different severities and explore its impact on cognition and brain microstructure in non-demented elderly. Lesions were both qualitatively (Fazekas scale) and quantitatively assessed among 321 community-dwelled individuals with MRI scanning. Voxel- and atlas-based analyses of the whole-brain white matter microstructure were performed. The WMH of the same severities was found to occur uniformly with a specific pattern of lesions. The severity of WMH had a significant negative association with the performance of working and episodic memory, beginning to appear in Fazekas 3 and 4. The white matter tracts presented significant impairments in Fazekas 3, which showed brain-wide changes above Fazekas 4. Lower FA in the superior cerebellar peduncle and left posterior thalamic radiation was mainly associated with episodic memory, and the middle cerebellar peduncle was significantly associated with working memory. These results support that memory is the primary domain to be affected by WMH, and the effect may potentially be influenced by tract-specific WM abnormalities. Fazekas scale 3 might be the critical stage predicting a future decline in cognition.

Progression of Microstructural Degeneration in Progressive Supranuclear Palsy and Corticobasal Syndrome: A Longitudinal Diffusion Tensor Imaging Study.

Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) are both 4 microtubule binding repeat tauopathy related disorders. Clinical trials need new biomarkers to assess the effectiveness of tau-directed therapies. This study investigated the regional distribution of longitudinal diffusion tensor imaging changes, measured by fractional anisotropy, radial and axial diffusivity over 6 months median interval, in 23 normal control subjects, 35 patients with PSP, and 25 patients with CBS. A mixed-effects framework was used to test longitudinal changes within and between groups. Correlations between changes in diffusion variables and clinical progression were also tested. The study found that over a 6 month period and compared to controls, the most prominent changes in PSP were up to 3±1% higher rates of FA reduction predominantly in superior cerebellar peduncles, and up to 18±6% higher rates of diffusivity increases in caudate nuclei. The most prominent changes in CBS compared to controls were up to 4±1% higher rates of anisotropy reduction and 18±6% higher rates of diffusivity increase in basal ganglia and widespread white matter regions. Compared to PSP, CBS was mainly associated with up to 3±1% greater rates of anisotropy reduction around the central sulci, and 11±3% greater rates of diffusivity increase in superior fronto-occipital fascicules. Rates of diffusivity increases in the superior cerebellar peduncle correlated with rates of ocular motor decline in PSP patients. This study demonstrated that longitudinal diffusion tensor imaging measurement is a promising surrogate marker of disease progression in PSP and CBS over a relatively short period.

White matter integrity of the cerebellar peduncles as a mediator of effects of prenatal alcohol exposure on eyeblink conditioning.

Fetal alcohol spectrum disorders (FASD) are characterized by a range of neurodevelopmental deficits that result from prenatal exposure to alcohol. These can include cognitive, behavioural, and neurological impairment, as well as structural and functional brain damage. Eyeblink conditioning (EBC) is among the most sensitive endpoints affected in FASD. The cerebellar peduncles, large bundles of myelinated nerve fibers that connect the cerebellum to the brainstem, constitute the principal white matter element of the EBC circuit. Diffusion tensor imaging (DTI) is used to assess white matter integrity in fibre pathways linking brain regions. DTI scans of 54 children with FASD and 23 healthy controls, mean age 10.1 ± 1.0 years, from the Cape Town Longitudinal Cohort were processed using voxelwise group comparisons. Prenatal alcohol exposure was related to lower fractional anisotropy (FA) bilaterally in the superior cerebellar peduncles and higher mean diffusivity (MD) in the left middle peduncle, effects that remained significant after controlling for potential confounding variables. Lower FA and higher MD in these regions were associated with poorer EBC performance. Moreover, effects of alcohol exposure on EBC decreased significantly after inclusion of these DTI measures in regression models, suggesting that these white matter deficits partially mediate the relation of prenatal alcohol exposure to EBC. The associations of greater alcohol consumption with these DTI measures are largely attributable to greater radial diffusivity, possibly indicating poorer myelination. Thus, these data suggest that fetal alcohol-related deficits in EBC are attributable, in part, to poorer myelination in key regions of the cerebellar peduncles.

[Bilateral middle cerebellar peduncle infarcts caused by bilateral vertebral artery occlusion: a case report].

Patients with bilateral vertebral artery occlusion have a high incidence of cerebral infarction with poor prognosis. Infarction of bilateral middle cerebellar peduncle (MCP) is extremely rare and only a few cases have been reported in literature. A 74-year-old male patient was admitted to our hospital with a chief complaint of dizziness and walking instability for 13 d. Brain magnetic resonance image showed acute bilateral middle cerebellar peduncle infarction. Digital subtraction angiography showed occlusion of the initiation part of left vertebral artery and whole right vertebral artery, while a large amount of collateral circulations and recanalization were observed. After volume expansion, anti-platelet aggregation and lipid-lowering therapy, the symptoms disappeared. The patient was followed up for 10 months and he recovered well.

Oculopalatal tremor, facial myokymia and truncal ataxia in a patient with neurosarcoidosis.

Symptomatic palatal tremor (SPT) is the result of a structural lesion, in the form of stroke, trauma or demyelinating disease. SPT is due to contractions of the levator veli palatini and can be accompanied by simultaneous movements of the facial and ocular muscles. Facial myokymia (FM) is a persistent quivering of the facial muscles. FM is usually encountered with conditions involving the pontine tegmentum. We report, to our knowledge, the first patient with neurosarcoidosis with simultaneous SPT and FM. A 49-year-old African American woman, with non-caseating granulomas in a paratracheal lymph node biopsy, presented with progressive gait disturbances for the last 3 years. Neurological examination revealed ataxic speech, bilateral rotatory nystagmus, myokymia of the chin and perioral muscles, palatal tremor without ear click and marked truncal ataxia. MRI demonstrated a lesion involving the facial nucleus and the right middle cerebellar peduncle. Based on exclusion of alternative etiologies, a diagnosis of neurosarcoidosis was made and the patient was started on methotrexate for 9 months, with minimal improvement. She was then switched to intravenous infliximab without major adverse events. The patient's speech and gait ataxia improved and follow up MRI demonstrated resolution of the enhancing lesions. To our knowledge, this is the first reported case of the combination of palatal tremor and FM due to neurosarcoidosis. Methotrexate may fail to produce clinical or radiographic response in up to 39% of patients. Tumor necrosis factor-α inhibitors, such as infliximab, should be considered in refractory cases.

Structural and functional brain changes beyond visual system in patients with advanced glaucoma.

In order to test the hypothesis that in primary open angle glaucoma (POAG), an important cause of irreversible blindness, a spreading of neurodegeneration occurs through the brain, we performed multimodal MRI and subsequent whole-brain explorative voxelwise analyses in 13 advanced POAG patients and 12 age-matched normal controls (NC). Altered integrity (decreased fractional anisotropy or increased diffusivities) of white matter (WM) tracts was found not only along the visual pathway of POAG but also in nonvisual WM tracts (superior longitudinal fascicle, anterior thalamic radiation, corticospinal tract, middle cerebellar peduncle). POAG patients also showed brain atrophy in both visual cortex and other distant grey matter (GM) regions (frontoparietal cortex, hippocampi and cerebellar cortex), decreased functional connectivity (FC) in visual, working memory and dorsal attention networks and increased FC in visual and executive networks. In POAG, abnormalities in structure and FC within and outside visual system correlated with visual field parameters in the poorer performing eyes, thus emphasizing their clinical relevance. Altogether, this represents evidence that a vision disorder such as POAG can be considered a widespread neurodegenerative condition.