NEURO

SOX2 (OMIM: 184429) encodes for a transcription factor of the SRY (sex-determining region Y)-related high-mobility-group box family which regulates pluripotency of human embryonic stem cells and is indispensable for coordinated embryogenesis. Pathogenic variants within this gene are associated with autosomal dominant syndromic forms of uni- or bilateral micro- or anophthalmia and a wide range of non-ocular features including neurological, gastrointestinal, genital, skeletal, cardiovascular, endocrine and renal anomalies [1]. from Journal of the Neurological Sciences http://bit.ly/2Im1J0k

from Neurology recent issues http://bit.ly/2YXewfI

T2-weighted MRI brain scans in older people commonly reveal diffuse white matter hyperintensities (WMH). These changes often accompany focal, lacunar ischemic lesions and likely constitute a feature of sporadic small vessel disease (SVD). 1 from Neurology recent issues http://bit.ly/2U4KRxt

Innumerable explanations have been put forth for the failures that have occurred in translating promising preclinical and early-phase treatments in ischemic and hemorrhagic stroke. In their work over the last decade, neurologists Mandava and Kent have promulgated their own unique theory. 1,2 In essence, they posit that phase 3 trials that failed were destined to fail because they were based on false-positive phase 2 trials. They believe that false-positive results arise because of (1) the difficulty in achieving randomization balance in baseline factors that influence outcome; (2) the noise generated by errors in subjective outcome measures; and (3) the complex, nonlinear relationships between baseline factors and outcomes that often violate assumptions required for typical statistical methods intended to correct for imbalances and noise. They assert that these factors together have contributed to misleading early-phase results that ultimately led to failed late-phase trials. from

An estimated two-thirds of boys with adrenoleukodystrophy (ALD) will develop cerebral ALD lesions during their lifetime, with the most concentrated period occurring in the first decade (figure). 1,2 Although the pathogenic triggers and risk factors responsible for the genesis of these inflammatory demyelinating lesions remain poorly characterized, the lesions themselves are fairly stereotyped in their anatomical origins, histologic features, and general trajectory. from Neurology recent issues http://bit.ly/2U1XFo9

While multiple sclerosis (MS) has classically been considered to be a white matter disease, it is now clear that gray matter changes are seen at onset. Importantly, regional gray matter atrophy correlates strongly with motor outcomes in adult patients. 1 Individuals with pediatric-onset MS have greater disease burden, as evidenced by higher relapse rate 2 and increased lesion volume and atrophy on MRI 3 than those with adult-onset MS. Furthermore, cognitive decline may be seen as early as 2 years after diagnosis in this population. 4 Importantly, studies of structural correlates of disease progression in pediatric-onset MS must take the dynamic and maturational changes known to occur in the pediatric brain into account, including age- and sex-specific growth in some areas and regression and pruning in others. 5 To this end, previous studies focused on white matter tracts and head size in pediatric-onset MS, and showed alterations in growth trajectories in patients with pediatric-o

Slow-release dimethyl fumarate (DMF) is the most widely prescribed oral disease-modifying therapy (DMT) for relapsing-remitting multiple sclerosis (RRMS). Class I evidence indicates that DMF reduces relapse rates, MRI disease activity, and, to a lesser extent, disability progression in RRMS. 1,2 Apart from flushing, gastrointestinal symptoms, and (infrequently severe) lymphopenia, the drug is well-tolerated. Real-world comparison of oral DMTs showed slightly variable results, but suggest that DMF is roughly similar in reducing relapses compared to other oral DMTs, that is, fingolimod and teriflunomide, 3 especially when used in naive patients. 4 from Neurology recent issues http://bit.ly/2U4njsk

While women have entered the academic (and nonacademic) neurology task force in large numbers, few have reached high visibility and decision-making positions in the field. A peculiarity of the field of multiple sclerosis (MS) includes the substantial financial aspect associated with marketing of expensive drugs, which has contributed to an influential leadership model marked by inequities. 1,2 Efforts to address gender gaps now and in the future require reliable metrics of the current status of women in neurology. from Neurology recent issues http://bit.ly/2YXevbE

Articles appearing in the August 2018 issue from Neurology recent issues http://bit.ly/2TZEWK0

A 54-year-old woman with a large right petroclival meningioma (figure 1) reported spontaneous spinning vertigo, oscillopsia, and right-sided "clicking" tinnitus lasting 5–30 seconds, recurring every 5–10 minutes. Examination with video-Frenzel goggles revealed flurries of spontaneous right-beating, horizontal-torsional (irritative) nystagmus, time-locked with vertigo (video 1). Hearing was symmetrical with right vestibular hypofunction affecting all 3 semicircular canals and the saccule (figure 2). Vestibular paroxysmia was diagnosed and carbamazepine 100 mg BD was prescribed. The patient was asymptomatic at 4 weeks. Eighth cranial nerve neurovascular cross-compression may cause vestibular paroxysmia characterized by brief spells of spontaneous and positional vertigo associated with unilateral audiovestibular deficits. 1,2 from Neurology recent issues http://bit.ly/2YZFsv5

When we land, Guinea is bright and damp, the air settling like a heavy coat against our arms as we walk off the plane. The sun is shining through wispy clouds, and the sunset seems to last forever, pink and lavender behind the domes and minarets of the mosque. The hospital is on a spit of land that juts into the Gulf of Guinea. Two men paddle away from the shore in a little boat that crests and falls with the wind like a rocking horse. Further out are cargo ships, so gray and still that at first they seem like boulders. from Neurology recent issues http://bit.ly/2U4uctJ

Using the prospective observational Atherosclerosis Risk in Communities cohort, Rawlings et al. sought to determine an independent association between orthostasis and risk of stroke and dementia. After adjustment for known vascular risk factors and other medical history that are associated with stroke and dementia risk, the investigators found an independent association between orthostatic hypotension (OH) and stroke (hazard ratio [HR] 2.08, 95% confidence interval [CI] 1.65–2.62) and dementia (HR 1.54, 95% CI 1.20–1.97) throughout the 16-year follow-up period. from Neurology recent issues http://bit.ly/2Z1XoFN

I read with interest the study by Rawlings et al., 1 which showed an association between orthostatic hypotension (OH) and future risk of dementia. The article proposed a causative effect of OH, in addition to associated cardiovascular risk factors. The evidence presented, however, does not support this view. The strong association between OH and various cardiovascular risk factors—such as diabetes, smoking, hypertension, and antihypertensive drugs—is well-known. These increase risk of vascular dementia, and a majority of Alzheimer cases show increased cerebral vascular burden at autopsy. 2 However, patients with OH without hypertension no longer showed significant association with cognitive decline. 1 Presenting the raw data from the subgroup of patients without any cardiovascular risk factors would be helpful. from Neurology recent issues http://bit.ly/2U1XGIJ

Rawlings et al. 1 reported that orthostatic hypotension (OH) was significantly associated with subsequent dementia and ischemic stroke. In contrast, there was no significant association between OH and cognitive decline. I have some concerns with this study. from Neurology recent issues http://bit.ly/2YYcYSD

We thank Dr. Young for his insightful comment. While there is a biologically plausible mechanism by which orthostatic hypotension (OH) may affect cognition, we agree that our results also support the idea that OH may operate primarily through vascular processes and may simply be a biomarker of elevated vascular risk; this is supported by our results that OH appeared detrimental in persons with hypertension and diabetes, as noted in the Discussion. 1 from Neurology recent issues http://bit.ly/2U1sLfS

Using 3 prospective observational cohorts including 1,288 patients with available clinical and pathologic data, Arvanitakis et al. estimated the association between longitudinal blood pressure (BP) measures and the risk of histopathologic cerebral infarctions. The investigators observed that, for a patient whose mean systolic BP (SBP) was 1 SD above the cohort's mean SBP, that patient would be at a 46% increased risk of any cerebral infarction. from Neurology recent issues http://bit.ly/2YTAyA1

We read with interest the article by Arvanitakis et al., 1 which found that both higher mean and more rapidly declining late-life systolic blood pressure (SBP) increased the odds of gross and microinfarcts. A relationship between higher mean SBP and neuronal neurofibrillary tangles was also observed. In examining blood pressure (BP) and neuropathology of aging, recent work highlighted that high—but also low BP—and wide fluctuations of BP levels may increase the risk of dementia, including mixed or Alzheimer dementia. 2–4 In addition, antihypertensive medications can specifically address the pulsatile component and variability of BP. 4,5 Therefore, it would be interesting to explore whether and how BP variability and pulse pressure relate to brain disease. These analyses would be useful to further understand the vascular contribution to cognitive dysfunction and identify potential therapeutic strategies. from Neurology recent issues http://bit.ly/2U69M3N

We appreciate the interest in our study on late-life blood pressure (BP) and postmortem neuropathology in nearly 1,300 community-dwelling, autopsied persons. 1 While we chose to separately examine longitudinal systolic BP (SBP) and diastolic BP (DBP) data, and indeed found more robust associations of a higher mean and more rapidly declining SBP with neuropathology, we agree that examining other BP variables provides additional insight into this area of research. Using the same datasets and a similar analytic approach of adjusted ordinal regression analyses, we found consistent results using additional BP variables. Increased variability in SBP over the years ( p = 0.002), but not variability in DBP ( p = 0.945), was associated with increased odds of brain infarcts, and increased mean pulse pressure over the years increased the odds of infarcts by 24% ( p < 0.001). In adjusted linear regression analyses, there was no relation of variability in SBP or DBP with neurofibrillary tang