A rehab therapy useful for MS

When patients with Multiple Sclerosis—and other chronic debilitating diseases—start losing the motor function of the upper and/or lower extremities, they feel rightly frustrated. The inability to write steadily, grab a cup, walk without falling and similar common activities will limit their interaction with family, friends and co-workers, leading to anxiety and depression. The chronic pain can be managed more efficiently than the forced isolation due to the above.

Some clinical trials have suggested that MS patients might benefit from several rehabilitation techniques, but they were short in duration and did not answer the fundamental question; can the techniques learned in the rehabilitation clinic be transferred to the patients’ homes efficiently? A new study claims that the “Constraint-induced movement therapy” (CIMT) used in the rehab of stroke patients can be useful, even with short practice runs, in the care of MS motor limitations.

VW Mark et al. designed a Phase II randomized clinical trial with 20 participants that had hemiparetic MS and were assigned either to a 35 hours-training in CIMT or alternative medicine. The CIMT intervention, done on ten consecutive days, had the following components:

  1. Intensive training with the limited extremity for basic activities for three hours/day.
  2. Training with “behavioral shaping”: try to achieve motor goals progressively and with constant encouragement from the therapist, even for small gains.
  3. Restraint of the less compromised limb to prod the use of the affected one.
  4. Use of a “transfer package” to stimulate the practice at home, which included a contract, practice homework, keeping a diary and a 30 minute-daily interview with the therapist.

The participants were evaluated with the “Motor Activity Log” (MAL), a scripted interview to compare the gains from the use of the technique with the previous functional baseline. The participants in the control group did aquatic therapy, yoga and other relaxation techniques. For the group that underwent CIMT there was a mean change in MAL of 2.7 after one year, compared to 0.5 in the control group. A change of 1.0 was considered clinically meaningful for participants; auspiciously, all the CIMT patients and three of the control group reached that clinical goal.

In the second stage of this same study, the researchers studied whether the practice of CIMT could promote changes in the white matter of MS patients with Magnetic Resonance Imaging (MRI) techniques such as T1 weighted scans and whole brain diffusion tensor scans. They found that there were improvements in the white matter of the corticospinal tract, temporal and visual areas. These extraordinary findings were in line with previous data obtained form monkeys in labs. If the neuroplasticity of the nervous tissue can warrant significant clinical changes after just a few days of focused, personalized rehabilitation for MS patients, this technique must be transferred home with a special package. Patients and their families would certainly be more than willing to try it.

Patients with MS should be aware that physical defeat only comes when they “throw the towel into the ring.” They should never, ever give up hope.

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Drug overdose and suicide in Epilepsy

One of the most devastating piece of news physicians can get is that one of our familiar patients has died, not of natural causes or the pathological progression of a disease, but due to suicide. The correct treatment of Epilepsy requires a longstanding relationship with the patients and their families, trying to seek a seizure-free environment so they can have a fruitful, enjoyable lifestyle. Unfortunately, too much attention is being given to medication and little to depression and anxiety.

Dr. Harley C. Gorton directed a study in the United Kingdom that canvassed two large primary care-data sets, the Clinical Practice Research Datalink (CPRD) in England and the Secure Anonymized Information Linkage (SAIL) Databank in Wales, in order to detect unnatural deaths in epileptic patients. Oftentimes the certificate of death of patients do not list Epilepsy as a contributing factor, which severely limits the study of that condition’s morbidity and mortality. Those two databases are linked to hospitalization, outpatient care centers and death records. This study suggested that physicians should pay more attention to co-morbid conditions like anxiety, depression and substance abuse, plus monitor the use of opioids and psychotropic medication.

In this study the researchers matched 44,678 participants with Epilepsy in the CPRD database to 891,429 participants without it in a period spanning from 1998 to 2014; they matched 14,051 participants with the disease in the SAIL database to 279,365 people from 2001 to 2014. Epileptic patients were 2.77 times more likely to die of an unnatural cause, 2.97 times more likely to die of unintentional injury or poisoning, and 2.15 times as likely to die of suicide. People taking medication had 4.99 times higher risk of collateral effects and 3.55 times higher risk of misuse. The most widely abused medication were opioids (56.5%) and psychotropic agents (32.3%)

The researchers stated that “patients should be adequately advised about unintentional injury prevention and monitored for suicidal ideation, thoughts and behavior.” They also said that “the suitability and toxicity of concomitant medication should be considered when prescribing for comorbid conditions.” The care personnel should understand that “good seizure control” is not limited to just a proper medication schedule to obtain a good quality of life for the patients. An excessive focus on seizure control in the follow-up of epileptic patients will sideline the necessary screening for psychiatric and behavioral health issues with the timely referral to other specialists.

It is extremely uncomfortable to discuss the issue of “mental health” with our patients and their families in our medical offices, especially because an archaic stigma lingers on in our societies. However, we must start the discussion in a respectful way, without alarming them excessively; we must stress out that we want to offer them information, without suggesting any particular venue. Sometimes epileptic patients have difficulties to access the mental health care services because the payors will not cover the expenditures, or they lack the proper information due to a disconnect. Our personal attitudes towards these patients must include a greater dosage of sympathy for them.

Suicide Prevention Hotline 1-888-628-9454/ www.suicidepreventionlifeline.org

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A new drug for progressive Multiple Sclerosis

Multiple Sclerosis is not a single pathological entity but rather two abnormal processes that advance in parallel yet inter-connected tracks and varying degrees of severity, which results in different clinical presentations. In the beginning the infiltrative inflammation predominates in the brain and spinal cord with the clinical imprimatur of relapses and remissions. Patients, who are usually young, have the illusion that once the inflammation process subsides, they would be disease-free for a long time.

However, a more sinister and crippling process has already started: degeneration. The clinical picture consists of progression with limiting sequelae like chronic pain and spasticity of upper and lower limbs. The available drugs targeted the first process but failed to address the second one. Until a new drug was studied: siponimod. Like fingolimod, it is a modulator of sphingoside-1-phosphate (SIP) receptors but it only selectively modulates types 1 and 5 receptors of the lymphoid tissue; the first one promotes the disposal of lymphocytes while the second one is stored in the CNS.

Kapos et al. collected more than 1600 patients from almost 300 clinical centers in the USA and Europe to study the administration of 2 mg of sipominod per day to half the cohort to compare it to the other half that only received a placebo for a median period of eighteen months. The principal studied index was “time to three-month confirmed disease progression” (CPD), which was defined as a 1.0 point increase in expanded Disability Status Scale (EDSS) score for the participants with moderate disability or 0.5 point increase for those with severe disability initially.

Only 26% of participants receiving siponimod had grave, prolonged disability compared to 32% of those receiving only the placebo; the drug had a hazard ration of 0.79 and a relative reduction of 21% of the risk to develop crippling symptoms. Once the study was finished all the participants were offered the chance to take it. Imaging studies showed a reduction from baseline in T2 lesion volume and the gadolinium-enhancing lesions. Moreover, those participants taking the drug had less decline in the brain volume between the 12th and 14th months compared to placebo.

Investigators are moderately optimistic about these results, but they point out that, in order to prevent the serious disabilities this disease provokes in young people, they must strive to intervene earlier in progressive forms of MS. Much, much earlier.

What do you think? Please tell us.

Don’t leave me alone.

Hearing loss and Cognitive decline

They say that we wouldn’t be able to tolerate the smell of the Middle Ages, a pervasive stench produced by the dumping of all the raw sewage in the small, congested streets; citizens had the chance to cloister themselves in their homes with incense and spices. But those same citizens wouldn’t be able to function anywhere with our noise pollution.

In our modern hyper-connected age, there are many causes of hearing loss due to the constant bombardment of noise in the public media that is transmitted to people’s personal devices, inside and outside their homes. A significant hearing loss (more than 20 decibels) manifested in the elevation of the threshold for pure detection affects almost half of people over 65 years old and two thirds of those above 80. The loss of hearing does affect the mental capacity of patients, being an important dementia cause. If the hearing loss is greater than 25 decibels, the patient will age approximately 7 years more.

The sense of Hearing has two main neurological components, which are the following:

  1. Peripheral Hearing: it includes all the sensory elements of the outer and middle ear that receive and transmit the encoded sensations to the Central Nervous System.
  2. Central auditory processing (CAP); it includes all the CNS structures involved in the hearing pathway that ends up in the Temporal lobe.

From the paraphernalia of sounds that we are being exposed to on a daily basis, our nervous system must separate the important sounds and “classify” them before their distribution to the brain; our encoding system allows us to differentiate the pitch, rhythm and timbre of the incoming noises. As we age the central processing of sounds progressively deteriorate and affects a majority of people. A clinical study involving 120 participants with a mean age of 70 years old found that the cognitive decline was related to understanding of speech in noise and not the peripheral pick-up of sounds.

RK Gurgel et al. studied a large cohort of 4,545 individuals with a mean age of 75 years old and no clinical signs of any cognitive decline; the clinical examination showed that 836 individuals had baseline hearing loss. All the study participants were subsequently followed for almost 12 years. In the hearing loss group 16% eventually showed signs of cognitive decline and in the normal group 12% did; the mean time to show signs was 10.3 years in the first group and 11.9 in the other. An additional 10% of the patients with hearing loss that developed cognitive decline eventually showed signs of Alzheimer’s disease, compared to 8% of those that did not have any hearing loss.

Lin MY et al. found that study participants with hearing loss had a significant increase in cognitive decline—almost 40% in some cases—and almost a quarter of those with abnormal hearing did develop cognitive decline in the follow-up period of six years; those with hearing loss took on average 7.7 years to show intellectual deterioration compared to 11 years for those without it. It’s a self-sustaining vicious circle as another study showed that dementia worsens hearing loss.

Jonathan Peelle et al showed that impaired hearing capacity is associated with the decrease in the critical volume of gray matter in the auditory cortex bilaterally, as well as the one of the prefrontal cortex; as the study was not longitudinal, it is not clear whether these finding were before or after the loss. Profant et al., using the novel radiological techniques of MR morphometry and Diffuse tensor imaging (DTI),  showed that hearing loss can produce deterioration of the white matter coming in and out of the auditory cortex, suggesting that age alone is not the only factor in cognitive decline; the hearing loss can lead to sensory deprivation, wrong information processing and anatomy changes.

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Botox for Chronic Migraines

As Botox has become more popular in the treatment of Chronic Migraines, treating physicians must make sure that their diagnosis is appropriate in order to get maximum the benefit from it. The patient should have had at least four episodes, each one with at least two of these features:

  1. Unilateral distribution (one-sided)
  2. Pulsatile quality (throbbing)
  3. Moderate or severe pain (a least 5/10)
  4. Worsened by physical activities

They must have at least one of the following: nausea or vomiting or sensitivity to light or noise.

Patients have an aura when the visual effects precede the actual episode at least by five minutes; it usually involves an expanding blind spot or some visual scintillations (shimmering objects) An aura can also manifest itself by difficulties of speech and/or language like missing words or inability to spell certain ones. It could also involve sensory phenomena like dysesthesias in the upper or lower extremities, muscular weakness, gait imbalance or cranial nerve problems.

Episodic migraines occur when the patient has 14 or fewer episodes per month. Chronic Migraines occur when the patient has 15 or more episodes per month. If the patient has headaches more than half the number of days in a month, with characteristic features in 8 of them, then he/she has CM.

The Food and Drug administration (FDA) has only approved Onabotulinum toxin A for the use in Chronic Migraines so far; its safety and efficacy were proved in the phase III of the “Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) where the participants were treated every 12 weeks, whether or not their episodes had ameliorated or there was a good outcome after 2 treatment cycles. On average the study participants had 19 episodes per month and after treatment with Botox they had 8-9 episodes less. A quarter of these patients improved by a 75% reduction.

Only a 30G or 31 G half-inch needle should be used for injections as longer needles penetrate deeper with the consequent risk of muscle weakness and associated cervical pain. Preservative-free normal saline is the only accepted solution to dilute the drug before the injection. With an effective dose using 2ml/100 units of Onabotulinum A, a mean dosage of 165 should be used.

In order to avoid the collateral effect of ptosis, the frontalis muscle should be carefully injected; the needle should not be moved higher or pointed up.in order to avoid diffusion of the liquid to it. Following the PREEMPT guidelines, one injection at a 45% angle of 5 units of Onabotulinum A should be injected in four different places of the frontalis muscle (for a total amount of 20 units)

If the patient had pre-existing cervical pain and/or weakness, the injection of the drug in the occipitalis, paraspinal or trapezius muscles can worsen that symptom and the ensuing limitations. Following the PREEMPT guidelines, 5 units of Onabotulinum A should be administered at two different places on both the right and left sides for a total dosage of 20 units at four different sites.

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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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