Lisa Kinsley

ALS untangled no. 20: The Deanna protocol

ISSN 2167-8421 print/ISSN 2167-9223 online

ALSUntangled: Introducing the table of evidence

We found no precedent for grading the types of evidence we review, so we used a ‘ crowd sourcing ’ approach to create the TOE. One ALSUntangled reviewer (RB) constructed a fi rst draft. The rest of the review team then suggested edits via emails over two months. Finally a subset of reviewers met in person and validated the utility of the TOE by attempting to convert the evidence from all 26 prior ALSUntangled reviews into this.

Reproductive decision-making among individuals at risk for familial amyotrophic lateral sclerosis

Abstract This qualitative study explored the reproductive decision-making process in individuals at 50% risk for familial amyotrophic lateral sclerosis (FALS) from families with a known genetic mutation. We spoke with 10 individuals utilizing a semi-structured interview. Participants had a first-degree relative with FALS, made reproductive decisions in the past 30 years and did not know their genetic status during decision-making. We delineated themes emerging in individuals who chose to have children, those who chose not to have children, and themes describing the process in general. Results showed that those who chose to have children believed that regardless of disease, life is productive. They compared ALS relatively favorably to other diseases, always planned on having children, and hoped for a cure. Individuals who chose not to have children had extensive experience with ALS and caretaking, saw ALS as an inevitable tragedy, and avoided serious relationships. In consultation with partners, individuals considered other reproductive options. Conversations varied in length, and often strengthened relationships. Children experiencing death of a parent was a primary concern. In conclusion, the reproductive decision-making process is complex. Results can guide future research and provide direction for healthcare professionals when discussing the family planning process and prior to predictive genetic testing.

ALS untangled no. 17: "When ALS Is Lyme"

ISSN 1748-2968 print/ISSN 1471-180X online

ALSUntangled No. 16: Cannabis

ISSN 1748-2968 print/ISSN 1471-180X online

ALS untangled 15: Coconut oil

ISSN 1748-2968 print/ISSN 1471-180X online

The Impact of Family History on the Clinical Features of Huntington's Disease

BACKGROUND Huntingtons disease (HD) is an autosomal dominant neurodegenerative disorder. In most cases the disease is inherited from a parent, although a considerable number of affected persons have no reported family history of the disease. While CAG repeat length is negatively correlated with age of symptom onset, variability exists suggesting that other variables may influence symptom onset. OBJECTIVES The objective of this study is to determine whether awareness of a family history of HD has an impact on symptom onset and disease manifestations. METHODS Data were obtained from Enroll-HD to compare subjects with a family history of HD to subjects without on various key clinical outcomes. In addition, multiple regressions were performed to investigate the impact of family history on the age at onset of depression and motor symptoms. RESULTS 4,285 mutation positive subjects were included in the analysis, of which 4.81% had a negative family history. Controlling for CAG repeat length, a positive family history predicted an onset of depression 11.438 years earlier and an onset of motor symptoms 6.681 years earlier when compared to having a negative family history. Subjects with a positive family history were more likely to report behavioral manifestations as the initial major symptom of HD (38.6% vs. 29.6%, p = 0.023), and were more likely to report previous suicidal ideation/attempts (26.2% vs. 20.3%, p = 0.046). CONCLUSIONS A positive family history of HD appears to be associated with an earlier onset of depression and overall disease manifestations. Implications regarding the role of genetic versus environmental contributions to symptom onset in HD are discussed.

ALSUntangled No. 37: Inosine*

Urate (sometimes referred to as uric acid) is a naturally occurring antioxidant (5,6). Interest in urate as a possible neuroprotective agent began when researchers noted that high urate levels are associated with lower risk of developing Parkinson’s disease (7–9) and Alzheimer’s disease (10). Naturally occurring high levels of urate are also associated with slower disease progression in Parkinson’s disease (11–13). The biological mechanisms that cause ALS are not completely understood, but they are likely to include damage to the motor neurons from oxidative stress, as supported by both autopsy and laboratory studies (14). It follows that antioxidants such as urate (or agents that increase levels of these such as inosine) might theoretically be neuroprotective in ALS. Some (15–18) but not all (19–22) studies find that high urate is associated with prolonged survival in PALS. Further database analyses and clinical trials are underway to try and clarify this. Beyond just neuroprotection via urate elevation, recent work suggests that inosine can stimulate the growth of axons in culture, promote collateral sprouting in the corticospinal tract, and even enhance motor recovery after traumatic brain injury (23). These observations suggest that inosine might be able to enhance reinnervation in ALS. ALSUntangled assigns a TOE ‘Mechanism’ grade of C based on this information (Table I).

ALSUntangled No. 36: Accilion

Accilion is a topical mineral cream advertised by Advanced Mineral Compounds, LLC (AMC, 2). It is one of several products with different names and websites (Table I) that trace their origin to a botanist named John Wayne Kennedy (20) and his patent entitled ‘Bioavailable minerals for plant health’ (19). Three of these products are topical mineral creams while a fourth is a mineral supplement marketed to be sprayed on agricultural crops to promote disease resistance and improve growth. These products appear to have similar ingredients and similar proposed mechanisms, and nearly identical description by which they claim to distinguish themselves from other mineral compounds (Table I). A representative from AMC has told us that these products are different in important ways including ‘‘zinc/copper ratios’’ and ‘‘redox’’, that there is a legal dispute underway between the current owners, and that ‘‘efforts to have these compounds independently assessed and thoroughly verified are now routinely obstructed’’ (21). Interestingly, the same cancer-patient testimonials appear for three of these products and the same ALS-patient testimonial appears for two of them (Table I).

ALSUntangled No. 35: Hyperbaric Oxygen Therapy*

HBOT involves treating patients with 100% oxygen at pressures several times higher than atmospheric pressure. This is accomplished by placing patients in a sealed, pressurized chamber (2). HBOT was initially used to treat decompression sickness after diving. There are currently 14 approved, evidencebased indications for HBOT including treatment of air embolism, carbon monoxide poisoning, nonhealing wounds (such as diabetic wounds), burns, gangrene, brain abscess, and radiation injury (3). Numerous websites advertise off-label HBOT for a wide variety of other conditions including multiple sclerosis, dementia, stroke and ALS (4,5). Metaanalyses conclude that there is insufficient evidence to support the use of HBOT in multiple sclerosis (6), dementia (7) and stroke (8). The FDA has warned patients against such off-label use (9).