Yoga and Exercise in early Parkinson’s disease

The emergence of a hyper-connected society where patients routinely check new information about treatments and medications for their diseases has completely changed the parameters that a modern medical practice operates in large, urban centers. Patients ask many questions. Patients with Parkinson’s disease and their relatives ask what non-invasive cures might exist.

The practice of Yoga has been shown to improve the muscle strength, flexibility and balance of its regular practitioners; however, its impact dynamic factors like gait, reactive balance and proprioception was not studied until a group studied the effects of a new meditation program.A new study found that YoMed was as effective as the Proprioception Training (PT) to improve the proprioception, balance and power in older patients that had suffered at least one traumatic fall.

Sixteen patients with Parkinson’s disease were randomly assigned to either the YoMed or the Propioception Training groups and they all received 45 minutes of training, three times per week for a total number of six weeks; patients were evaluated before and after the interventions. Neither the YM or the PT interventions showed statistical significant results except for the “dynamic posturography overall score” (DMA) that was readily improved in the YM group. Thus, YoMed might be clinically useful to improve the posture abnormalities in older PD patients.

Many patients are diagnosed with Parkinson’s disease based on the clinical symptoms but, given that they do not warrant starting a medication schedule yet, many of them ask physicians what they should be doing to slow the progression of this scary disease. Exercise comes to mind first. A study from the Physical Therapy department of the University of Colorado School of Medicine shows that an early start of high-intensity treadmill exercise might accomplish that benefit.

Schenkman et al. designed the “Study in Parkinson’s Disease of Exercise’ (SPARX) by studying 128 patients enrolled between 2012 and 2015, had between 40 and 80 years of age, were within five years of a diagnosis and were not exercising at moderate intensity more than 3 times per week; they were not taking any dopaminergic medication and were not expected to take it soon. They were divided into three groups as follows:

  1. High Intensity group of 43 patients that exercised four days a week at 80-85% of their maximum heart rate.
  2. Moderate Intensity group of 45 patients that also exercised four days a week but at 60-65% of their maximum heart rate.
  3. A control group of 40 patients that did not exercise.

The clinical outcomes were measured primarily by using the change of the motor scores in the “Unified Parkinson’s Disease Rating Scale” (UPDRS) from a baseline level and a six-month mark; the secondary outcomes were measured with the UPDRS subscores and the “Movement Disorders Society UPDRS” (MDS-UPDRS) The participants wore portable heart rate monitoring devices to measure the exercise intensity. The mean change in UPDRS score in the high intensity score was 0.3 compared to 3.2 in the control group; the mean change of UPDRS scoring in the moderate intensity group was 2.0. There were no serious collateral effects in this study. The data shows that high intensity-exercise is a viable alternative to defer the onset of grave PD signs. This phase 2 study is being followed by a more complex phase 3 study to provide more information.

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New test for Alzheimer’s Disease

One of our earliest articles in 2016 for this series of “Wellness” was a discussion of how dedicated researchers had found two new substances to tag in patients with Alzheimer’s disease. This grave pathology can go almost undetected for many years and diagnosis usually comes late. The new focus of pharmacological research has changed to the earliest stages of the disease when amyloid starts to build up in the brain and drugs might make a difference; in order to achieve that a new laboratory test is needed.

A new report in Nature shows that a novel blood test that measures the amyloid biomarkers could be a reliable predictor of the presence of amyloid plaques in Alzheimer patients’ brains. Drs. Nakamura and Villemagne, from research centers in Japan and Australia respectively, described initial results on a blood test for amyloid-beta 9Abeta) that is similar to an earlier test developed by another team in Washington University of Saint Louis. At present researchers believe that the deposition of amyloid plaques can precede at least twenty years the first signs of cognitive decline, for which it is critically important to detect it early on to cure the patients.

The blood testing method consisted of isolating and concentrate three amyloid peptides (Abeta40, Abeta42 and APP699-71) from a sample that contained thousands of other proteins. They took advantage of data from two different cohorts of participants (some normal, some with mild cognitive decline and others with severe Alzheimer’s disease) that were studied previously in Japan (121 people) and Australia (252 people) where they compared the results of positron emission tomography (PET) with the testing of cerebrospinal fluid for amyloid. They calculated ratios of the different amyloid biomarkers and a composite score of multiple biomarkers; a rise in the composite index suggested that there was an active accumulation of amyloid in the brain.

The researchers claim that there was a 90% accuracy rate and a high correlation between the blood and cerebrospinal fluid tests. This test is more cost-effective than other types of testing, which could be the determinant factor in its approval by the public and private payors. It is still being developed and available only in the research labs.

There is a critical need for a safe and practical laboratory test to diagnose Alzheimer’s disease to screen the potential participants in clinical trial studies that usually span for several years. Participants that were initially deemed to have early signs of the disease—a diagnosis that is often very difficult for clinicians—ended up as not having it, which skewed the study results. Getting the right participants into the numerous studies underway is of humongous importance to find safe drugs to use early on.

Researchers are still tweaking the test to find out if it could be used to differentiate Alzheimer’s from other causes of cognitive decline like Lewy body dementia or Frontal lobe dementia; they also want to know if it can be used to track the progression or the disease or to assess the clinical response of patients to new drugs.

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The “broken heart” syndrome

The massive influx of women in the workforce of modern nations has produced a widespread phenomenon of “double stress” in their lives as they usually must cope with the work and household requirements at the same time. Even though there has been a shift in the social customs as more men are becoming aware that they must share the household chores, including the rearing of children, there is still an asymmetry in the distribution of tasks. Women still work more. Much more.

Sadly, the recent statistics show that women are catching up with the morbidity and mortality due to cardiovascular diseases due to their newfound responsibilities. In the USA it is the leading cause of death and disability for women of all societal levels. Oftentimes the presentation of cardiovascular disease is atypical in women as they do not show up in the office with the traditional “angor pectoris”; they have persistent anxiety or asthenia or polymorphic pain syndromes in the extremities.

Early in their lives, the estrogens have a protective effect on their cardiovascular system as they promote the formation of HDL-cholesterol, which cleanses the vessels of atherosclerotic plaques. But as menopause approaches, they have less estrogens and the risk of cardiovascular anomalies increases significantly.

As women usually have a richer emotional dimension, there are more instances where they can suffer from an “emotional frustration” and bear consequences. In post-menopausal women an unusually strong emotional event can produce a particular syndrome called “Takotsubo’s cardiomyopathy”. The sudden release of a high amount of adrenalin produces transitory damages to the cardiac muscle with the corresponding clinical presentation mimicking a “heart attack” due to coronary artery disease; the laboratory values and electrocardiogram may be abnormal.

The angiography shows an increase dilatation of the left ventricle, which normally has a triangular shape; it becomes more elongated and rounded, resembling an inverted vase. The Japanese physicians that discovered this clinical syndrome in 1990 named it after the special utensil Japanese fishermen use to catch octopus. Once the acute episode subsides with proper medical therapy, the heart recovers completely and there are no permanent sequelae of a “broken heart” syndrome.

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Smoke cessation and Stroke

Cessation of Smoking has been repeatedly shown to be a critical factor in the prophylaxis and aftercare of cardiovascular diseases, especially Stroke. But it had not been properly studied with a rigorous scientific study until now.

Kathrine Epstein et al. compared the rates of the composite outcome of stroke, myocardial infarction or death during a period of five years in a cohort of patients that had had a recent ischemic stroke or transient ischemic attack and who were still smoking or had quit. The IRIS protocol included high quality baseline data on smoking and follow-up data on outcomes.

The IRIS study recruited 3,876 non-diabetic individuals that had had a stroke or a TIA in the past six months into a study whether pigliotazone could reduce the recurrence of these events in a five year-period; in 2015 they started studying patients from 179 hospitals and clinics in 7 countries. They studied several lifestyle measures, including smoking cessation, in the beginning of the study and then in a follow-up contact four times per year.

At the baseline 1,490 individuals were classified as former smokers, 450 as quitters after the CVA and 622 continued to smoke for a median time of 40 years. After a median follow-up of almost five years, 60 patients of non-smokers had a stroke, a myocardial infarction of passed away. The mortality was higher in individuals that were still smoking. Only 7 deaths in the quitting group were related to a neoplasia compared to 21 for the smokers (1.5% versus 3.4%) There was a more modest effect in cerebrovascular disease (0.2% versus 1.6%) and heart disease (0.7% versus 1.6%) The relative-risk reduction (34%) and the absolute risk reduction (6.9 %) are comparable to other clinical treatments for secondary stroke prevention.

Physicians should talk clear to their stroke patients that do not quit smoking. “Listen, of 100 persons that do not give up puffing after what you had, 23 of them will most likely have another stroke, a myocardial infarction or even pass away after five years…Do you want to continue playing this lottery?”

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Concussions and Multiple Sclerosis

For many years researchers have been studying the possible link between head concussions in early life and the onset of Multiple Sclerosis in later years. However the results have been disappointing except for a new study.

Montgomery, Hiyoshi et al. studied the large, prospective, collected data of the National Swedish patient register—with hospital diagnoses and the clinical data of patients diagnosed with MS—to compare the information of more than 2000 individuals diagnosed with MS up to 2012 who were matched with more than 72,000 non-MS ones, controlling for sex, year of birth, age and vital status at the time of diagnosis and county of diagnosis. The events of head concussion and broken bones in the extremities were singled out from birth to 10 years old, and from the ages of 11 to 20.

One single concussion occurring between the ages of 11 and 20 provoked an adjusted odds ration of teens later been diagnosed with MS of 1.22% while two or more concussions were associated with an odds ratio of 2.33. The investigators did not find any relationship between children aged 10 or younger who had head concussions with the later onset of the disease; the same was true for young people that had broken bones but no concussions. Interestingly enough they found that the longer the hospital stay for head concussion was, the more likely the possibility of developing MS also was; the odds ratio for developing MS following a single day of hospitalization was 1.15, compared to 1.55 for two days and 1.75 for three days or more.

Dr. Montgomery, professor of Clinical Epidemiology at Örebro University in Sweden, said “in adolescents with more than one concussion, it’s a doubling of the risk for MS. But the risk of developing MS is very low to begin with. That’s why we want to know more about susceptibility. That’s a study we’re going to do now, to look at genetic susceptibility. Then we might see a more precise estimate of risk for individuals.” A previous study showed that brain injury triggers an autoimmune process in nervous tissue. If a genetically susceptible individual has a brain lesion during adolescence, then the statistical possibility of developing MS later in life might increase.

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Neuromodulation for Migraines

For several years we have been using the TENS machines to stimulate the Peripheral Nervous System in order to get needed relief for chronic neuro-muscular problems. The same physiological principle is being used to stimulate the Central Nervous System. One of the stealthiest developments in the treatment of Migraines has been the technological development of devices that will control the episodes. Various regulatory issues have delayed their introduction in the commercial market but they will soon become an option if insurers start to cover them. Here is a review of the three devices that have been approved by the FDA.

Transcutaneous Supraorbital Neurostimulation. It is the first device that was approved by the FDA and its commercial name is “Cefaly.” It is applied on a set of electrodes on the forehead to stimulate both supraorbital nerves. According to a scientific study the device must be used for 20 minutes per day for at least three months in order to noticed a significant reduction of headache days. It has both a high-intensity and low-intensity settings in the USA; in the EU and Canada it has a preventive, acute and chronic settings. With an approximate cost of U$ 400, it is not yet covered by the Payors.

Single-Pulse Transcranial Magnetic Stimulation. The second approved device is a single-pulse transcranial magnetic stimulator that is commercially available under the name “Spring TMS”; it is applied in the back of the skull and sends pulses forward up to the frontal area. It blocks the slow activation of cortical neurons dubbed as “cortical spreading depression” (CSD) that forms the basis of the auras patients experiment before an attack. A study found it effective at the beginning to wipe out the aura and the expected fit; the FDA has approved the deployment of two pulses right before an attack. In a preventive mode, 4 pulses are applied in both the morning and at night.It is only available to rent for 3 months with a price of U$ 150 per month.

Non-invasive Vagal Nerve Stimulation. The third device is a stimulator of the vagus nerve placed on the neck that is used for cluster headaches and set at two cycles in the treatment and prevention protocols. Two studies have shown that it can end an acute episode of cluster headache but it was not effective in the treatment of chronic cluster attacks. Also not effective in chronic migraines after 2 months, it might be effective at longer time points. It can block the CSD and down-regulate the thalamo-cortical pathways.

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Fatigue in Multiple Sclerosis

Fatigue is the worst debilitating symptom of patients with MS (multiple sclerosis) as it severely limits their participation in the public sphere and the workforce, besides alienating their interpersonal relationships. It has a subjective component, i.e. how patients feel, and an objective one, i.e. the diminished performance in physical and intellectual tasks. Kluger et al. created a unified taxonomy to guide its treatment in the medical settings.

Perceived fatigue is what the patient actually feels at any given time; it can be defined as a lack of purpose in daily activities that hampers performance.

Fatigability (also called performance fatigability) is what can be objectively measured by an examiner; it is defined by the measure of change in the performance of a physical or a cognitive task over a certain period of time.

Perceived fatigue is measured by the “Neurological Fatigue Index” (NFI-MS), which was approved by the FDA. It is made of 23 standard questions that cover three domains of fatigue; physical, cognitive and sleep quality. It also has a summary scale that covers the physical and cognitive domains. Fatigability can be measured with a 6-Minute Walk Test (6MWT), a grip strength test and the response speed to different cognitive tests. The third measurement of fatigability is carried out with the “Continuous Performance Test” (CPT) that checks the timely attention in front of a computer screen.

Mayis Aldughmi et al. studied the perceived fatigability and fatigability in 52 patients with mild forms of MS with a mean age of 46 years. The percent change score of the 6MWT was not statistically associated with the physical domain, the cognitive domain or the summary scale. The grip strength test change scores were not statistically associated with physical domain, the cognitive domain or the summary scale. But the performance fatigability was statistically associated with the three parameters of the NFI-MS. The data illustrates that performance fatigability during an attention-based test is associated with increased physical and cognitive perceived fatigue and the overall perceived fatigue. However those assessments of performance fatigability during a physical task did not yield some significant results. This study showed that the presence of depression was associated with fatigue.

In this study MS patients had fatigue after 3 performance fatigability tests: walking, handgrip and attention. Only attention had a statistically significant association with perceived fatigue, unlike the other 2 performance measures.

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