Phenytoin may be neuroprotective on outcomes in optic neuritis.

Background

Acute demyelinating optic neuritis, a common feature of multiple sclerosis, can damage vision through neurodegeneration in the optic nerve and in its fibres in the retina. Inhibition of voltage-gated sodium channels is neuroprotective in preclinical models. In this study we aimed to establish whether sodium-channel inhibition with phenytoin is neuroprotective in patient with acute optic neuritis.

Methods

We did a randomised, placebo-controlled, double-blind phase 2 trial at two UK academic hospitals in London and Sheffield. Patients with acute optic neuritis aged 18–60 years, presenting within 2 weeks of onset, with visual acuity of 6/9 or worse, were randomly assigned (1:1) by minimisation via a web-based service to oral phenytoin (maintenance dose 4 mg/kg per day if randomised before or on July 16, 2013, and 6 mg/kg per day if randomised on or after July 17, 2013) or placebo for 3 months, stratified by time from onset, centre, previous multiple sclerosis diagnosis, use of disease-modifying treatment, and use of corticosteroids for acute optic neuritis. Participants and treating and assessing physicians were masked to group assignment. The primary outcome was retinal nerve fibre layer (RNFL) thickness in the affected eye at 6 months, adjusted for fellow-eye RNFL thickness at baseline, analysed in a modified intention-to-treat population of all randomised participants who were followed up at 6 months. Safety was analysed in the entire population, including those who were lost to follow-up. The trial is registered with ClinicalTrials.gov, number NCT 01451593.

Findings

We recruited 86 participants between Feb 3, 2012, and May 22, 2014 (42 assigned to phenytoin and 44 to placebo). 29 were assigned to phenytoin 4 mg/kg and 13 to phenytoin 6 mg/kg. Five participants were lost to follow-up, so the primary analysis included 81 participants (39 assigned to phenytoin and 42 to placebo). Mean 6-month RNFL thickness in the affected eye at 6 months was 81·46 μm (SD 16·27) in the phenytoin group (a mean decrease of 16·69 μm [SD 13·73] from baseline) versus 74·29 μm (15·14) in the placebo group (a mean decrease of 23·79 μm [13·97] since baseline; adjusted 6-month difference of 7·15 μm [95% CI 1·08–13·22]; p=0·021), corresponding to a 30% reduction in the extent of RNFL loss with phenytoin compared with placebo. Treatment was well tolerated, with five (12%) of 42 patients having a serious adverse event in the phenytoin group (only one, severe rash, was attributable to phenytoin) compared with two (5%) of 44 in the placebo group.

Interpretation

These findings support the concept of neuroprotection with phenytoin in patients with acute optic neuritis at concentrations at which it blocks voltage-gated sodium channels selectively. Further investigation in larger clinical trials in optic neuritis and in relapsing multiple sclerosis is warranted.

Fundoscopic Photography With the iPhone 5 and Welch-Allyn PanOptic Opthalmoscope

Although detailed fundoscopic photography is usually the province of the retinal specialist, I think that there is a place for fundus photography in neurology, especially improving on the standard of writing down our documentation of optic disc abnormalities such as atrophy or pailledema. This is especially true with the advent of better quality cameras in our cell phones.

Welch-Allyn has made an adapter for the iPhone4 to allow fundus photography with their excellent Panoptic opthalmoscope, but they do not plan to make one that fits other phones, at least so far. However, there are a number of inexpensive brackets made for microscopes to allow cellular phones to take photomicrographs, and they do allow the Panoptic opthalmoscope to be used with the Welch-Allyn iPhone retinal photography app, called the iExaminer (available for iPhone to go with the iPhone 4 adapter, and not to my knowledge available for Android).

The cell phone/eyepiece bracket I ordered for the purpose arrived yesterday. I'll post about my experience later.

If cetaceans have culture, can the Star Wars universe be said to exist in reality?

Bizzare rhetorical questions make such fun titles, don't you think? Anyway--

As discussed last year, there is good cumulative evidence that whales and dolphins have culture, where culture is defined as non-genetic information passed from animal to animal. Is culture something that exists objectively? Certainly dolphin behavior as it is influenced by dolphin culture is objectively observable. So, dolphin culture, to the biologist who accepts such evidence, is an objectively detectable thing, even if it is not a material object. A neutral monist might say it was a non-material existent component of the dolphins who carry that culture, composed of complexly structured non-material relationships accompanying the material stuff of the dolphin pod and its environment, and perhaps a non-monist like Popper would say it is a part of his "World 3".

What does it mean for culture to exist? If culture exists, can it do so independently of the material artifacts it produces and that in turn produce it? Or is it a supervenient property of such objects? Culture certainly seems more than just a property of brain tissue.

As Brandon of the Siris blog commented recently, fictional characters like those of the Sherlock Holmes or, more popular recently, the Star Wars fictional worlds exist as cultural artifacts that affect our speech and other behavior just as other cultural artifacts such as political laws and boundaries do. The boundary of a state is in one sense a material location, and in another it is a regulation or law as it applies to that location. The boundary can be seen as a nonmaterial thing with a physical location, like the culture of the dolphin pod, which is located with the pod but is not really made of the material stuff of the pod. So, a political boundary is a cultural, non-material property of culture, not a real fence, made by government, and is not a material thing itself, any more than the planet Tatooine in Star Wars becomes a material thing if we locate it "in a galaxy far, far away."

One difference between fictional entities and legal entities is in the link to specific locations in the material world and the causality on our behavior we attribute to a political boundary. Political boundaries, with their institutional and military implications, seem much more powerfully causal than than the locations and characters of fictional stories.

There seems to be a sense in which fictional characters, governmental laws, and other parts of our cultural stories truly exist, but as non-material existences, like the abstract structure of mathematics. Meinong's golden mountain is part of our intellectual culture, and, like dead fish-play dolphin fads and Star wars light swords, such shared imaginings are are a nonphysical part of the cultures on our earth. If such bits of culture exist merely as behavioral aspects of the organisms making up a society, they are far from epiphenomenal ones. Is a hurricane just a property of air and water?

Governmental structures merely seem more firmly linked to the material aspects of our world and as such are more powerfully causal than most fiction. Yes, this seems to be a form of Platonism, unless we claim instead that all culture reduces to information encoded in material objects. Such "encoding" cannot be said to fully exist without its meaning, however, and meaning itself seems to be a paradigm of the non-material existent.

Electronic toys that emit sounds may slow language development in infants.

Electronic toys for infants that produce lights, words and songs were associated with DECREASED development quantity and quality of language compared to playing with books or traditional toys such as a wooden puzzles, shape-sorters or rubber blocks, according to an article published online by JAMA Pediatrics. The study was controlled, with a 15 minute per day session with the toys, infant, and parent. The effect was not small: about a third fewer adult words produced by study's end.

Surprising? Yes. So, for the time being, we should not get electronic toys for infants, and maybe, by extrapolation, preschoolers. It might slightly decrease their speech development. The Luddite mothers win this round :).

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ABSTRACT

Original Investigation | December 23, 2015

Association of the Type of Toy Used During Play With the Quantity and Quality of Parent-Infant Communication

Anna V. Sosa, PhD

JAMA Pediatr. Published online December 23, 2015. doi:10.1001/jamapediatrics.2015.3753

Importance The early language environment of a child influences language outcome, which in turn affects reading and academic success. It is unknown which types of everyday activities promote the best language environment for children.

Objective To investigate whether the type of toy used during play is associated with the parent-infant communicative interaction.

Design, Setting, and Participants Controlled experiment in a natural environment of parent-infant communication during play with 3 different toy sets. Participant recruitment and data collection were conducted between February 1, 2013, and June 30, 2014. The volunteer sample included 26 parent-infant (aged 10-16 months) dyads.

Exposures Fifteen-minute in-home parent-infant play sessions with electronic toys, traditional toys, and books.

Main Outcomes and Measures Numbers of adult words, child vocalizations, conversational turns, parent verbal responses to child utterances, and words produced by parents in 3 different semantic categories (content-specific words) per minute during play sessions.

Results Among the 26 parent-infant dyads, toy type was associated with all outcome measures. During play with electronic toys, there were fewer adult words (mean, 39.62; 95% CI, 33.36-45.65), fewer conversational turns (mean, 1.64; 95% CI, 1.12-2.19), fewer parental responses (mean, 1.31; 95% CI, 0.87-1.77), and fewer productions of content-specific words (mean, 1.89; 95% CI, 1.49-2.35) than during play with traditional toys or books. Children vocalized less during play with electronic toys (mean per minute, 2.9; 95% CI, 2.16-3.69) than during play with books (mean per minute, 3.91; 95% CI, 3.09-4.68). Parents produced fewer words during play with traditional toys (mean per minute, 55.56; 95% CI, 46.49-64.17) than during play with books (mean per minute, 66.89; 95% CI, 59.93-74.19) and use of content-specific words was lower during play with traditional toys (mean per minute, 4.09; 95% CI, 3.26-4.99) than during play with books (mean per minute, 6.96; 95% CI, 6.07-7.97).

Conclusions and Relevance Play with electronic toys is associated with decreased quantity and quality of language input compared with play with books or traditional toys. To promote early language development, play with electronic toys should be discouraged. Traditional toys may be a valuable alternative for parent-infant play time if book reading is not a preferred activity.

An alternative to Kim's physicalism

In his book Physicalism, or Something Near Enough , Jaegwon Kim says: The final picture that has emerged is this: P is a cause of P*, wi...