AAN issues new guidelines for choosing disease-modifying treatments for multiple sclerosis.

The number of treatments released for MS has been growing steadily in the last 10 years. The American Academy of Neurology has issued guidelines to help with choice of treatment. One new feature of the guidelines is several recommendations that may cause a change in treatment from one medication to another in certain clinical settings--something there has been little consensus on in prior years.

Here's a summary, with italics for "must" (level A) recommendations and bolded text where potential treatment-changing recommendations are made (those are at the lesser "should" level, B):
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Starting DMT: Recommendations

Statement 1

Clinicians should counsel people with newly diagnosed MS about specific treatment options with DMT at a dedicated treatment visit (Level B).

Statement 2a

Clinicians must ascertain and incorporate/review preferences in terms of safety, route of administration, lifestyle, cost, efficacy, common adverse effects (AEs), and tolerability in the choice of DMT in people with MS being considered for DMT (Level A).

Statement 2b

Clinicians must engage in an ongoing dialogue regarding treatment decisions throughout the disease course with people with MS (Level A).

Statement 3a

Clinicians should counsel people with MS that DMTs are prescribed to reduce relapses and new MRI lesion activity. DMTs are not prescribed for symptom improvement in people with MS (Level B).

Statement 3b

Clinicians must counsel people with MS on DMTs to notify the clinicians of new or worsening symptoms (Level A).

Statement 4

Clinicians should evaluate readiness or reluctance to initiate DMT and counsel on its importance in people with MS who are candidates to initiate DMT (Level B).

Statement 5

Clinicians should counsel about comorbid disease, adverse health behaviors, and potential interactions of the DMT with concomitant medications when people with MS initiate DMTs (Level B).

Statement 6a

Clinicians should evaluate barriers to adherence to DMT in people with MS (Level B).

Statement 6b

Clinicians should counsel on the importance of adherence to DMT when people with MS initiate DMTs (Level B).

Statement 7a

Clinicians should discuss the benefits and risks of DMTs for people with a single clinical demyelinating event with 2 or more brain lesions that have imaging characteristics consistent with MS (Level B).

Statement 7b

After discussing the risks and benefits, clinicians should prescribe DMT to people with a single clinical demyelinating event and 2 or more brain lesions characteristic of MS who decide they want this therapy (Level B).

Statement 8

Clinicians may recommend serial imaging at least annually for the first 5 years and close follow-up rather than initiating DMT in people with CIS or relapsing forms of MS who are not on DMT, have not had relapses in the preceding 2 years, and do not have active new MRI lesion activity on recent imaging (Level C).

Statement 9

Clinicians should offer DMTs to people with relapsing forms of MS with recent clinical relapses or MRI activity (Level B).

Statement 10a

Clinicians should monitor for medication adherence, AEs, tolerability, safety, and effectiveness of the therapy in people with MS on DMTs (Level B).

Statement 10b

Clinicians should follow up either annually or according to medication-specific REMS in people with MS on DMTs (Level B).

Statement 11

Clinicians should monitor the reproductive plans of women with MS and counsel regarding reproductive risks and use of birth control during DMT use in women of childbearing potential who have MS (Level B).

Statement 12

Clinicians should counsel men with MS on their reproductive plans regarding treatment implications before initiating treatment with teriflunomide or cyclophosphamide (Level B).

Statement 13

Because of the high frequency of severe AEs, clinicians should not prescribe mitoxantrone to people with MS unless the potential therapeutic benefits greatly outweigh the risks (Level B).

Statement 14

Clinicians should prescribe alemtuzumab, fingolimod, or natalizumab for people with MS with highly active MS (Level B).

Statement 15a

Clinicians may direct people with MS who are candidates for DMTs to support programs (Level C).

Statement 15b

Clinicians may recommend azathioprine or cladribine for people with relapsing forms of MS who do not have access to approved DMTs (Level C).

Statement 16

Clinicians may initiate natalizumab treatment in people with MS with positive anti-JCV antibody indexes above 0.9 only when there is a reasonable chance of benefit compared with the low but serious risk of PML (Level C).

Statement 17

Clinicians should offer ocrelizumab to people with PPMS who are likely to benefit from this therapy unless there are risks of treatment that outweigh the benefits (Level B).

Switching DMT: Recommendations

Statement 1a

Clinicians should monitor MRI disease activity from the clinical onset of disease to detect the accumulation of new lesions in order to inform treatment decisions in people with MS using DMTs (Level B).

Statement 1b

Clinicians should recognize that relapses or new MRI-detected lesions may develop after initiation of a DMT and before the treatment becomes effective in people with MS who are using DMTs (Level B).

Statement 1c

Clinicians should discuss switching from one DMT to another in people with MS who have been using a DMT long enough for the treatment to take full effect and are adherent to their therapy when they experience 1 or more relapses, 2 or more unequivocally new MRI-detected lesions, or increased disability on examination, over a 1-year period of using a DMT (Level B).

Statement 2

Clinicians should evaluate the degree of disease activity, adherence, AE profiles, and mechanism of action of DMTs when switching DMTs in people with MS with breakthrough disease activity during DMT use (Level B).

Statement 3

Clinicians should discuss a change to noninjectable or less frequently injectable DMTs in people with MS who report intolerable discomfort with the injections or in those who report injection fatigue on injectable DMTs (Level B).

Statement 4a

Clinicians should inquire about medication AEs with people with MS who are taking a DMT and attempt to manage these AEs, as appropriate (Level B).

Statement 4b

Clinicians should discuss a medication switch with people with MS for whom these AEs negatively influence adherence (Level B).

Statement 5a

Clinicians should monitor laboratory abnormalities found on requisite laboratory surveillance (as outlined in the medication's package insert) in people with MS who are using a DMT (Level B).

Statement 5b

Clinicians should discuss switching DMT or reducing dosage or frequency (where there are data on different doses [e.g., interferons, teriflunomide, azathioprine]) when there are persistent laboratory abnormalities (Level B).

Statement 6a

Clinicians should counsel people with MS considering natalizumab, fingolimod, rituximab, ocrelizumab, and dimethyl fumarate about the PML risk associated with these agents (Level B).

Statement 6b

Clinicians should discuss switching to a DMT with a lower PML risk with people with MS taking natalizumab who are or become JCV antibody–positive, especially with an index of above 0.9 while on therapy (Level B).

Statement 7a

Clinicians should counsel that new DMTs without long-term safety data have an undefined risk of malignancy and infection for people with MS starting or using new DMTs (Level B).

Statement 7b

If a patient with MS develops a malignancy while using a DMT, clinicians should promptly discuss switching to an alternate DMT, especially for people with MS using azathioprine, methotrexate, mycophenolate, cyclophosphamide, fingolimod, teriflunomide, alemtuzumab, or dimethyl fumarate (Level B).

Statement 7c

People with MS with serious infections potentially linked to their DMT should switch DMTs (does not pertain to PML management in people with MS using DMT) (Level B).

Statement 8a

Clinicians should check for natalizumab antibodies in people with MS who have infusion reactions before subsequent infusions, or in people with MS who experience breakthrough disease activity with natalizumab use (Level B).

Statement 8b

Clinicians should switch DMTs in people with MS who have persistent natalizumab antibodies (Level B).

Statement 9a

Physicians must counsel people with MS considering natalizumab discontinuation that there is an increased risk of MS relapse or MRI-detected disease activity within 6 months of discontinuation (Level A).

Statement 9b

Physicians and people with MS choosing to switch from natalizumab to fingolimod should initiate treatment within 8–12 weeks after natalizumab discontinuation (for reasons other than pregnancy or pregnancy planning) to diminish the return of disease activity (Level B).

Statement 10a

Clinicians should counsel women to stop their DMT before conception for planned pregnancies unless the risk of MS activity during pregnancy outweighs the risk associated with the specific DMT during pregnancy (Level B).

Statement 10b

Clinicians should discontinue DMTs during pregnancy if accidental exposure occurs, unless the risk of MS activity during pregnancy outweighs the risk associated with the specific DMT during pregnancy (Level B).

Statement 10c

Clinicians should not initiate DMTs during pregnancy unless the risk of MS activity during pregnancy outweighs the risk associated with the specific DMT during pregnancy (Level B).

Stopping DMT: Recommendations

Statement 1a

In people with RRMS who are stable on DMT and want to discontinue therapy, clinicians should counsel people regarding the need for ongoing follow-up and periodic reevaluation of the decision to discontinue DMT (Level B).

Statement 1b

Clinicians should advocate that people with MS who are stable (that is, no relapses, no disability progression, stable imaging) on DMT should continue their current DMT unless the patient and physician decide a trial off therapy is warranted (Level B).

Statement 2a

Clinicians should assess the likelihood of future relapse in individuals with SPMS by assessing patient age, disease duration, relapse history, and MRI-detected activity (e.g., frequency, severity, time since most recent relapse or gadolinium-enhanced lesion) (Level B).

Statement 2b

Clinicians may advise discontinuation of DMT in people with SPMS who do not have ongoing relapses (or gadolinium-enhanced lesions on MRI activity) and have not been ambulatory (EDSS 7 or greater) for at least 2 years (Level C).

Statement 3

Clinicians should review the associated risks of continuing DMTs vs those of stopping DMTs in people with CIS using DMTs who have not been diagnosed with MS (Level B).

JAMA takes the red pill.

HERE (image from xkcd).

Dead space and snorkeling deaths on Maui

There were quite a few more than usual snorkeling drownings off the shores of Maui last year. Some of the newer full face masks for snorkeling may be to blame. Although the original models were quite close fitting in the face, clone models may have had enough dead space in the mask between the face and visor to explain passing out during their use leading to drowning.

What is dead space and how does it cause high CO2 pressures? As explained on this poster, we rely on almost completely emptying ourselves of the exhausted air we breathe out to prevent sucking carbon dioxide back into our bodies with our next breath. Too much re-circulation of exhaled air in a full face mask can defeat effective exhalation, allowing toxic levels of carbon dioxide to accumulate.

Cataract surgery and cognitive function

How did cataract surgery improve cognitive performance in the elderly without affecting the risk of true dementia? Likely by improving the ability of elderly persons to stay better informed of their environment, including their test settings. Some types of cognitive dysfunction are of sensory perception more than sensory processing.

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ABSTRACT

Effect of cataract surgery on cognitive function in elderly: Results of Fujiwara-kyo Eye Study

Kimie Miyata, Tadanobu Yoshikawa, Masayuki Morikawa, Masashi Mine, Nozomi Okamoto, Norio Kurumatani, Nahoko Ogata

Published: February 20, 2018

https://doi.org/10.1371/journal.pone.0192677

Purpose

To determine whether there is a significant association between prior cataract surgery and cognitive function in an elderly Japanese cohort.

Setting

Nara Medical University, Nara, Japan.

Design

The Fujiwara-kyo Eye Study was a cross-sectional epidemiological study.

Methods

The subjects were ≥ 68-years who lived in the Nara Prefecture and responded to recruitment notices. All of the subjects received comprehensive ophthalmological examinations, and answered questionnaires on their socio-demographic and medical history including prior cataract surgery. The association between prior cataract surgery and cognitive function was determined.

Results

A total of the 2764 subjects whose mean age was 76.3±4.8 years (±standard deviation) was studied. Of these, 668 individuals (24.2%) had undergone cataract surgery. Of these, 150 (5.4%) had dementia as determined by the Mini-Mental State Examination (MMSE) score ≤23, and 877 individuals (31.7%) had mild cognitive impairment (MCI; MMSE score 24–26). The subjects who had prior cataract surgery had significantly lower odds ratio (OR) of having MCI (OR = 0.78, 95% confidence interval; CI 0.64–0.96, P = 0.019) than those who had not had cataract surgery after adjusting for age, sex, body mass index, education, hypertension, diabetes, depression, and history of stroke. The OR was still lower when the visual acuity was also added to the adjusted factors (OR 0.79, 95% CI 0.64–0.97, P = 0.025). However, prior cataract surgery did not contribute significantly to the low OR for dementia.

Conclusions

Cataract surgery may play a role in reducing the risk of developing MCI independently of visual acuity but not for dementia

Jabuticaba, vintage 2017.

Or is that an arborage?

Final draft of NIH cell phone exposure study in rats does not show any brain tumor risk.

The final draft (not yet the officially published version) of the "TOXICOLOGY AND CARCINOGENESIS STUDIES IN Hsd:SPRAGUE DAWLEY SD RATS EXPOSED TO WHOLE-BODY RADIO FREQUENCY RADIATION AT A FREQUENCY (900 MHz) AND MODULATIONS (GSM AND CDMA) USED BY CELL PHONES " is out. Unlike the preliminary, midstudy data, there is no brain cancer or brain tumor risk found.

The Sprague-Dawley breed of rats seems prone to cardiac tumors, and there is a hint of an increase in the rats of those cardiac tumors in male but not female rats. Since, on the whole, these cardiac tumors do not tend to have any gender bias in rats in other studies, one finds even those results suspect.

Overall, there seems to be no real reason to avoid the use of cell phones because of cancer risk. I think that the study authors are writing as if they are really searching for a positive result in a study that had little to show.

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ABSTRACT

GSM- AND CDMA-MODULATED CELL PHONE RADIO FREQUENCY RADIATION

The predominant source of human exposure to radio frequency radiation (RFR) occurs through the use of cellular phone handsets. The Food and Drug Administration nominated cell phone RFR emission for toxicology and carcinogenicity testing in 1999. At that time, animal experiments were deemed crucial because meaningful human exposure data from epidemiological studies were not available. Male and female Hsd:Sprague Dawley SD rats were exposed to time-averaged whole-body specific absorption rates of Global System for Mobile Communications (GSM)- or Code Division Multiple Access (CDMA)-modulated cell phone RFR at frequencies of 900 MHz (herein referred to as “cell phone RFR”) in utero, during lactation, and after weaning for 28 days or 2 years. Genetic toxicology studies were conducted in rat peripheral blood erythrocytes and leukocytes, brain cells, and liver cells.

Under the conditions of this 2-year whole-body exposure study, there was some evidence of carcinogenic activity of GSM-modulated cell phone RFR at 900 MHz in male Hsd:Sprague Dawley SD rats based on the incidences of malignant schwannoma in the heart. The incidences of adenoma or carcinoma (combined) in the prostate gland, malignant glioma and benign or malignant granular cell tumors in the brain, adenoma of the pars distalis in the pituitary gland, pheochromocytoma (benign, malignant, or complex combined) in the adrenal medulla, and pancreatic islet cell adenoma or carcinoma (combined) may have been related to cell phone RFR exposure. There was no evidence of carcinogenic activity of GSM-modulated cell phone RFR at 900 MHz in female Hsd:Sprague Dawley SD rats administered 1.5, 3, or 6 W/kg. There was some evidence of carcinogenic activity of CDMAmodulated cell phone RFR at 900 MHz in male Hsd:Sprague Dawley SD rats based on the incidences of malignant schwannoma in the heart. The incidences of malignant glioma in the brain, adenoma of the pars distalis in the pituitary gland, and adenoma or carcinoma (combined) of the liver may have been related to cell phone RFR exposure. There was equivocal evidence of carcinogenic activity of CDMA-modulated cell phone RFR at 900 MHz in female Hsd:Sprague Dawley SD rats based on the incidences of malignant glioma in the brain and pheochromocytoma (benign, malignant, or complex combined) in the adrenal medulla.

Increases in nonneoplastic lesions in the heart, brain, and prostate gland of male rats, and of the heart, thyroid gland, and adrenal gland in female rats occurred with exposures to GSM cell phone RFR at 900 MHz. Increases in nonneoplastic lesions of the heart, brain, and prostate gland occurred in males, and of the brain in females exposed to CDMA cell phone RFR at 900 MHz.

Terror exposure and headache.

Stress has long been identified as a major causal factor in the occurrence of headaches. A recently published study in Norway looked at the survivors of a terrorist's attack on a boys camp in that country. Reference: HERE. This study showed a 4 fold increased incidence of tension and migraine headaches for those with terrorism exposure.