Spasticity in MND Improved With Cannabinoid Oral Spray


Nabiximols, a cannabinoid-based oral spray (Sativex, GW Pharmaceuticals) approved outside the United States for various multiple sclerosis (MS) symptoms, shows benefit in improving spasticity and pain in motor neuron disease when administered as an add-on to standard therapy, new research suggests.

“This study is, to our knowledge, the first randomized controlled trial of safety and efficacy of a pharmacological treatment for spasticity and the first trial of nabiximols in motor neuron disease,” write the authors in their article published online December 13 in Lancet Neurology.

“Our results suggest that the study drug is well tolerated and provides first evidence of efficacy in terms of controlling spasticity in patients with motor neuron disease.”

Current treatments commonly used for spasticity in motor neuron diseases such as amyotrophic lateral sclerosis (ALS), the most common and severe of these diseases, including baclofen, dantrolene, and benzodiazepines, lack evidence of efficacy in this context and are associated with undesirable side effects including increased muscle weakness or fatigue.

Nabiximols, an oral spray combining equal parts delta-9 tetrahydrocannabinol and cannabidiol (THC-CBD), has meanwhile gained favor in the treatment of spasticity in MS in countries outside of the United States where it is licensed, suggesting potential for efficacy in spasticity in other diseases.

For the current proof-of-concept study, first author Nilo Riva, MD, of the IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy, and colleagues enrolled 60 patients with at least 3 months of spasticity symptoms associated with known or suspected ALS or primary lateral sclerosis (PLS) who were already taking an anti-spasticity regimen for at least 30 days prior to enrollment.

Patients were randomized to add-on treatment with nabiximols at an escalated dose to a predefined level titrated over 14 days or placebo for 6 weeks.

The study reached its primary endpoint with improvement in spasticity, assessed by change in the spasticity score of the Modified Ashworth Scale (MAS), which measures intensity of muscle tone, by a mean of 0.11 (SD, 0.48) in the nabiximols group (n = 59) compared with a deterioration of a mean of 0.16 (SD, 0.47) in the placebo group (n = 30; P = .01) over the course of the study.

Greater improvements were also observed in pain scores, reported on a scale of 0 to 10, with nabiximols (-0.97 vs -0.06) and in patient-reported global impression of change (P = .001).

Although there were no significant differences in other secondary endpoints, including sleep quality, spasms, spasticity, strength, upper and lower motor neuron tests, and scores on the Amyotrophic Lateral Sclerosis Functional Rating Scale — Revised, the scores suggested some benefit, Riva told Medscape Medical News.

“Although the effects on spasms, sleep disruption, and spasticity NRS scores were not significant, the direction of change was consistently in favor of the active treatment, and the pain NRS score improved significantly in nabiximols recipients,” Riva said.

The improvement was especially notable considering the patients’ existing regimens were falling short, Riva explained.

“The first-line anti-spasticity medications, including general muscle relaxants such as baclofen or benzodiazepines, usually work for some time, but as disease evolves, which can happen in months in ALS, the muscle rigidity may increase and a good number of patients require new management options,” said Riva.

Improvement in pain, which is also reported with the use of cannabinoids in other conditions, is also notably important, considering that it is a common complaint among people with motor neuron disease, Riva added.

“Although pain is an often neglected symptom in motor neuron disease, its prevalence has been reported to be as high as 51% to 80%, it negatively affects quality of life, and it necessitates specific treatment in 37% to 39% of patients.”

Similar to a previous study of cramps in ALS, no significant changes specifically in the intensity of spasms were seen in the study.

There were no serious adverse events. Although 21 (72%) of participants in the nabiximols group had at least one potentially treatment-related adverse event, compared with four in the placebo group (13%), none of the patients permanently discontinued treatment during the double-blind phase.

Non-serious adverse events were described as modest and were consistent with those common to cannabinoid treatment: three patients in the nabiximols group temporarily discontinuing treatment, one because of nausea and anxiety, one who had influenza and experienced a fall, and one who had disease progression.

Although nabiximols contain THC, the psychoactive component of cannabis, Riva noted that the levels are much lower than those typically associated with cannabis.

“The maximal levels of THC in blood (Cmax) reached with this oromucosal spray medication are about 60 times lower than the levels reached through THC inhalation, so no psychoses-like effects were expected,” Riva said.

“The medication has been used in Europe by tens of thousands of multiple sclerosis patients [for] years without major psychoactive cases.”

Meanwhile, the THC is believed to have an important role in the anti-spasticity effect of nabiximols, Riva added. “The muscle relaxant effect of the medication has been related to low and continuous levels of THC, as well as analgesia.

“Cannabidiol alone has shown effect on epilepsy area, but not in a relevant manner on muscle relaxation or pain to my knowledge.”

After the 6-week double-blind phase of the study, all participants had the opportunity to enroll in an open-label phase, and among them, two patients did not continue and seven patients ended up withdrawing from the open-label phase because of side effects or disease progression.

Meanwhile, participants who had been in the placebo group showed substantial improvements in mean MAS scores during the open-label phase.

“The (extension findings) further support nabiximols’ efficacy, even if the open-label design excludes the possibility of drawing any definitive conclusion,” Riva said.

Limitations of the study include that the MAS, despite being the most used and best validated objective measure of spasticity, may not fully represent patients’ experience of spasticity, and self-reported measures may also fall short in accurately representing spasticity, the authors noted.

“The ideal objective measure of the highly complex symptom of spasticity does not exist,” they said.

In an accompanying commentary, Marianne de Visser, MD, PhD, professor of neuromuscular disorders at Amsterdam University Medical Centre, the Netherlands, noted that limitations of the study include a bias towards patients who primarily had involvement of upper motor neurons in the nabiximols group.

“These patients (with upper motor neuron involvement) could have benefited more than the 13 patients with classic ALS, which involves both upper and lower motor neurons,” de Visser said.

Further commenting to Medscape Medical News, de Visser added that focusing on spasticity as a prevailing symptom, in general, could be a limitation.

“As yet, there is still uncertainty of how much spasticity contributes to the disease burden in the so-called classical type of ALS — not only spasticity but also flaccid weakness,” she explained.

Although the cannabinoids have shown efficacy and safety in MS, de Visser noted that responses could be different in patients with motor neuron disease.

“The literature on the use of nabiximols in MS seems to be reassuring regarding side effects,” she said. “However, ALS/motor neuron disease is a totally different disease, so we need the larger trials as well in order to assess the adverse effects.”

“The evidence provided (in the current research), albeit in a proof-of-principle study, is encouraging, ” she added.

“Further studies with larger numbers of ALS patients are needed to assess whether nabiximols is not only leading to reduction of spasticity but also reduces disease burden and improves quality of life.”

GW Pharmaceuticals has already made waves in the cannabis-based drug market in the United States this year with its oral drug Epidiolex (cannabidiol), the first drug containing a purified drug component derived from cannabis to receive approval from the US Food and Drug Administration.

Years of Thyroid Monitoring Needed After MS Drug Alemtuzumab


Treatment with the multiple sclerosis (MS) drug alemtuzumab (Lemtrada, Genzyme/Sanofi) is associated with thyroid dysfunction and an increased risk of Graves disease that may have onset later than previously thought and therefore could require longer-term monitoring, according to results of one of the largest case series to date, spanning 20 years.

“Alemtuzumab is a highly effective therapy for relapsing-remitting MS, [with a] number needed to treat to benefit of five [and] number needed to treat for a serious adverse event of 148,” say Nadia Pariani, University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, United Kingdom, and colleagues.

“However, the development of thyroid autoimmunity months or years after treatment is a frequent complication, requiring ongoing biochemical surveillance for at least 4 years after alemtuzumab therapy to detect and treat thyroid dysfunction promptly,” they note in their article published in the Journal of Clinical Endocrinology and Metabolism.

The development of autoimmunity is established as the most notable adverse effect of alemtuzumab, a monoclonal antibody, with thyroid autoimmunity representing the most common form.

Physicians can expect to see more cases of thyroid dysfunction among these patients, the authors note. “Following recent regulatory approval of alemtuzumab for treatment of MS, endocrinologists will be required to manage this form of thyroid dysfunction more often,” they write.

Alemtuzumab was approved by the US Food and Drug Administration in 2014, with a boxed warning for risk of serious, sometimes fatal autoimmune conditions, and must be prescribed and distributed in the United States through a risk evaluation and mitigation strategy (REMS). It is also licensed in the European Union.

Commenting on the new study, Barbara S. Giesser, MD, vice-chair of neurology at the Ronald Reagan UCLA Medical Center, Los Angeles, California, noted that the evidence still suggests that the benefits of alemtuzumab in MS likely outweigh the risks in terms of thyroid dysfunction.

“For patients with aggressive or unstable MS, alemtuzumab is a very effective treatment option,” Giesser, who is a fellow with the American Academy of Neurology, told Medscape Medical News.

“Some other reports have suggested that alemtuzumab-associated thyroid dysfunction may be less troublesome than spontaneous thyroid disease, and in some cases remits spontaneously,” she said. “The risks for neurologic deficit from MS have to be weighed against the risk of developing autoimmune disease which can usually be effectively treated.”

Thyroid Dysfunction With Alemtuzumab: Fluctuating and Unpredictable

To better understand the nature of the thyroid dysfunction, Pariani and colleagues evaluated data on 248 patients with MS who were treated with alemtuzumab in clinical trials in the United Kingdom from 1993 to 2013.

They discovered 102 (41.1%) patients who went on to develop thyroid dysfunction, including 80 women and 22 men, with the cases primarily involving Graves disease (71.6%), consistent with prior research.

Although there was high variation in the time of onset of the thyroid dysfunction, the majority (89%) of cases occurred within 36 months of the last dose of alemtuzumab and 91% occurred within 4 years.

Contrary to previous studies, however, nine cases were considered “late-onset” thyroid dysfunction, including two cases at 5 years, four cases at 6 years, one case at 7 years, and two cases as late as 9 years following the last dose of alemtuzumab.

“In a previous clinical trial, risk of autoimmune dysfunction peaked at 12 to 18 months after last alemtuzumab treatment, with no recorded autoimmunity beyond 5 years after therapy,” the authors note.

To take a closer look at the course of thyroid dysfunction, Pariani and colleagues analyzed data on a subgroup of 71 patients who had information available at a median of just over 5 years (67 months; range, 6 to 251 months).

Of those, 52 (73.2%) developed Graves disease, with 10 (19.2%) developing fluctuating thyroid dysfunction.

All participants who developed Graves disease were treated with antithyroid drugs, and of the 47 patients who completed a course, 16 were in remission and one developed spontaneous hypothyroidism. Meanwhile, 30 (64%) required long-term treatment, including 17 who required radioiodine therapy, five who required thyroidectomy, and eight who required long-term antithyroid drug treatment.

Comparatively, about 50% of patients with conventional Graves disease (not associated with alemtuzumab) typically require long-term treatment, the authors note.

Further outcomes suggested fluctuating levels of thyroid-stimulating hormone receptor antibody (TRAb) in the patients: among three cases of thyroiditis and 16 cases of hypothyroidism, as many as 10 were positive for TRAb, five had antithyroid peroxidase antibody positivity only, and one was of uncertain etiology.

In addition, patients who developed hypothyroidism had surprisingly high TRAb levels (mean 30.4 IU/L, range, 3.9 to > 40 IU/L), the authors point out.

“Fluctuating thyroid status in Graves disease and unexpectedly high frequency of TRAb-positive hypothyroidism suggested changing activity of TRAb in this clinical context; we have documented the existence of both blocking and stimulating TRAb in these patients,” they explain.

The fluctuating courses of alemtuzumab-induced Graves disease, with swings from hyper- to hypothyroidism, or from hypothyroidism to normal thyroid function, in fact could be underestimated, they stress.

“A considerable proportion (16.4%) of our patients developed Graves disease with a fluctuating and unpredictable course, and it is conceivable that this is an underestimate, as frequent use of a block-and-replace antithyroid drug regimen may have masked additional cases.”

Longer Surveillance Needed for Those Taking Alemtuzumab

Although the specific mechanisms behind autoimmunity induced by alemtuzumab are not well understood, similar autoimmunity is seen in other treatment contexts, including bone marrow transplantation or HIV antiretroviral therapy, and Graves disease is also common during recovery from lymphopenia.

As reported by Medscape Medical News, recent research has shown alemtuzumab can have important benefits in relapsing-remitting MS that are maintained as far out as 7 years, and that study showed relatively low thyroid-related adverse events, reaching just 17% at year 3.

But a prior study detailed potentially life-threatening side effects with alemtuzumab, including eight cases of acute acalculous cholecystitis, two cases of hemophagocytic lymphohistiocytosis, and one occurrence of acute coronary syndrome.

“Based on our experience, we suggest close monitoring of thyroid function in patients with alemtuzumab-treated MS, particularly if they develop Graves disease, offering early definitive treatment in drug-refractory or fluctuating cases,” Pariani and colleagues reiterate.

Giesser agrees that these new results underscore the need for monitoring patients for thyroid disorders — and perhaps for longer than previously realized.

“This study should caution clinicians that autoimmune thyroid disease, while most common in the first 3 years after alemtuzumab therapy, may occur many years later, and there needs to be continued surveillance for this,” she concluded.

Balance and Eye Training Program Succeeds in MS Patients


Balance and fatigue outcomes improved even in patients with lesionsAction Points

An integrated program of balance and eye-movement exercises improved balance, dizziness, fatigue, and quality of life in people with multiple sclerosis (MS), researchers reported.

In a randomized controlled trial, MS patients who had at least minimally impaired balance and fatigue experienced improved outcomes with Balance and Eye-Movement Exercises for Persons with Multiple Sclerosis (BEEMS) training, even when brainstem or cerebellar lesions were present.

 In 6 weeks from baseline, BEEMS participants achieved greater improvements than controls in Computerized Dynamic Posturography-Sensory Organization Test (CDP-SOT) composite, Dizziness Handicap Inventory (DHI) total, Modified Fatigue Impact Scale (MFIS) total, and Short Form-36 Health Status Questionnaire (SF-36) mental and physical scores, reported Jeffrey Hebert, PT, PhD, of the University of Colorado School of Medicine in Aurora, and colleagues.

And at 14 weeks from baseline, they bettered controls in CDP-SOT composite, DHI total, MFIS total, and SF-36 mental and physical scores, they wrote in Neurology.

Response differences in patients with brainstem or cerebellar lesions were evident at 6 weeks, but not sustained at 14 weeks, they added.

“The results of this study should inform how we deliver balance retraining in a population at high risk of falls,” wrote Susan Bennett, DPT, EdD, of the University at Buffalo in New York, and Victoria Leavitt, PhD, of Columbia University Medical Center in New York City, in an accompanying editorial. “These findings are promising and encourage future work to further probe the benefits and mechanisms of BEEMS.”

“Most rehabilitation programs to improve balance have focused mainly on strength exercises and balance exercises that are not designed for the specific problems of people with MS,” Hebert said in a statement. “We wanted to see if performing balance and eye movement exercises while processing multiple different sensory information could help people improve their balance and fatigue issues.”

This investigation was a follow-up to a pilot study and was an examiner-blinded trial with three phases:

  • 2-week baseline phase
  • 6-week treatment phase 1
  • 8-week treatment phase 2

During the baseline phase, the researchers obtained outcome measures twice to control for learning effects of the dynamic posturography-based balance test.

Adult patients were included if they had clinically definite MS and the ability to ambulate 100 m with intermittent or unilateral constant use of an assistive device. “The inclusion of participants who required use of an assistive device is another strength of this study because these persons have a greater challenge with balance,” noted Bennett and Leavitt.

The researchers randomized 88 participants (44 BEEMS, 44 controls) and 76 patients completed the trial.

Participants were screened for balance (CDP-SOT ≤82 of 100) and fatigue (MFIS ≥22 of 84). The CDP-SOT cutoff is the clinically meaningful difference of 8 points below that of healthy adults, the authors noted; the MFIS score is greater than the clinically relevant change of 15 reported for pharmaceutical interventions.

 Patients performed BEEMS training twice weekly with supervision and daily at home. The program consisted of three components: standing on difference surfaces, mobility-based walking with and without head movements, and visual stability including voluntary saccadic movements, smooth pursuits, and gaze stability.

“Of specific interest in this study was the presence of unsteady gaze fixation, which may reduce eye-hand coordination, and dysmetric saccades, which may interfere with guided stepping,” Bennett and Leavitt noted.

Additional training included visual input alterations such as ball tossing, somatosensory alterations that involved changing surfaces, and vestibular input alterations that affected yaw and pitch directions and whole-body movements.

From baseline to 6 weeks, BEEMS participants experienced greater improvements than controls in CDP-SOT composite (model-estimated difference in change 4.9, P=0.006), DHI total (−13.5, P<0.0001), MFIS total (−11.4, P<0.0001), SF-36 Mental (5.6, P=0.0006), and SF-36 Physical (3.5, P=0.004) scores.

From baseline to 14 weeks, the BEEM group had better CDP-SOT composite (8.3, P< 0.0001), DHI total (−13.9, P<0.0001), MFIS total (−12.3, P<0.0001), SF-36 Mental (3.9, P=0.02), and SF-36 Physical (3.2, P=0.01) scores.

BEEMS participants with brainstem or cerebellar lesion involvement experienced greater improvements compared with those without in CDP-SOT composite (5.26, P=0.04) and MFIS total (−7.6, P=0.02) scores from baseline to 6 weeks, but those differences were not sustained by 14 weeks.

“Overall, these findings demonstrate that the BEEMS protocol improved balance, consistent with previous nonspecific intervention studies, and resulted in greater improvements of dizziness and fatigue,” the authors wrote. “These findings suggest that vestibular rehabilitation and eye/head/limb coordination under progressively more challenging conditions should be included in physical interventions.”

Study limitations included an insufficient sample size to compare BEEMS patients against controls by lesion/no lesion. Gait outcomes that challenge postural control and clinical measures of balance should be considered in the future, the authors noted. The only measures related to the vestibulo-ocular reflex were the gaze stabilization and dynamic visual acuity tests; future investigations should include direct assessments like the head impulse test, they added.

High levels of testosterone protect men from multiple sclerosis


https://speciality.medicaldialogues.in/high-levels-of-testosterone-protect-men-from-multiple-sclerosis/

First-Line Rituximab Bests Other MS Drugs in Sweden


Off-label rituximab (Rituxan) showed superior drug survival rates and better clinical efficacy as first-line treatment in relapsing-remitting multiple sclerosis (RRMS) compared with other common therapies, the latest in a series of a Swedish registry studies found.

Significantly more newly-diagnosed RRMS patients remained on rituximab each year than injectable interferon or glatiramer acetate (Copaxone), dimethyl fumarate (Tecfidera), fingolimod (Gilenya), or natalizumab (Tysabri), Fredrik Piehl, MD, PhD, of the Karolinska Institute in Stockholm, and colleagues reported online in JAMA Neurology.

Rituximab showed significantly fewer clinical relapses and less neuroradiologic disease activity than injectable drugs or dimethyl fumarate and borderline significance over fingolimod and natalizumab.

And in a Swedish county where rituximab was the main initial treatment for RRMS, patients demonstrated better outcomes than those who lived where other first-line disease-modifying treatments (DMTs) predominantly were used, the researchers noted.

“Collectively, our findings suggest that rituximab performs better than other commonly used disease-modifying treatments in patients with newly diagnosed RRMS,” they wrote.

Rituximab, which is used off-label for MS in the U.S. and other countries, is similar to ocrelizumab (Ocrevus); both target CD20 immune B-cells instead of T-cells. Last year, the FDA approved ocrelizumab for relapsing and primary progressive multiple sclerosis.

“This real-world usage paper represents a somewhat unique natural history experiment in that there are significant regional differences in the use of rituximab and other medicines in similar patients across Sweden,” John Corboy, MD, of the University of Colorado, who was not involved in the study, told MedPage Today.

“It further supports the concept that anti-CD20 molecules are not only more effective than what many consider to be first-line therapies, but, as noted in the clinical trials, they have an adverse event and tolerability profile that is equal to, if not better than, the same first-line therapies,” he added.

The study included 494 individuals in Stockholm and Vasterbotten counties who received a diagnosis of RRMS from Jan. 1, 2012 to Oct. 31, 2015. Patients were observed until April 30, 2016.

The primary outcome was discontinued therapy for any reason, including conversion to secondary progressive MS and pregnancy. Secondary outcomes were relapses, the presence of gadolinium-enhancing (Gd+) lesions on magnetic resonance imaging (MRI) scans, adverse events, and reasons why patients stopped treatment.

The median age of patients was about 34, and 32% were men. Of the total sample, 43.5% received an injectable DMT (interferon or glatiramer acetate), 24.3% received rituximab, 17.4% received dimethyl fumarate, 10.1% received natalizumab, 3.4% received fingolimod, and 1.2% received another initial treatment.

Regional preferences were clear: 42 of 52 patients (81%) in Vasterbotten received rituximab, compared to 78 of 442 (18%) in Stockholm.

 Overall, the annual drug discontinuation rate was significantly better for rituximab (0.03) than injectable treatments (0.53), dimethyl fumarate (0.32), fingolimod (0.38), and natalizumab (0.29). Compared with rituximab, adjusted hazard ratios for stopping treatment were 11.4 (95% 4.7-27.4) for injectable DMTs, 15.1 (95% CI 3.9-58.0) for dimethyl fumarate, 5.9 (95% CI 1.5-23.4) for fingolimod, and 11.3 (95% CI 3.2-39.4) for natalizumab.

Pregnancy (3.3%) was the most common reason why patients stopped rituximab. Breakthrough disease and adverse events were the most frequent reasons why patients stopped other therapies: 38.1% and 27.9% for injectable DMTs, 16.3% and 14.0% for dimethyl fumarate, and 23.5% and17.6% for fingolimod, respectively.

Patients treated with rituximab demonstrated fewer clinical relapses and less neuroradiologic disease activity than patients who received injectable DMTs or dimethyl fumarate. Rituximab also showed numerically lower relapse rates and Gd+ lesions than fingolimod and natalizumab, but those findings did not reach statistical significance.

“In conjunction with data from this and other research groups, this is a cogent argument that anti-CD20 DMTs should be strongly considered as not only appropriate for those with more severe disease or those switching off other highly effective therapies, but also should be considered — indeed, suggested — as first-line for the average newly diagnosed MS patient, without the interference of ‘step editing’ mandated by so many insurance companies,” Corboy noted.

Most arguments for starting with less effective DMTs center around safety and price, Piehl and colleagues noted. Newer, more effective agents have been associated with risks like progressive multifocal leukoencephalopathy and often command a much higher price.

“It is undisputed that the safety record of first-line injectable DMTs in use since more than two decades is superior to that of newer DMTs, which is of high relevance in particular for the risk-benefit assessment of long-term treatment in patients with mild to moderate disease,” they wrote. Rituximab’s off-label status remains a barrier, too, subjecting it to varying insurance regulations.

This study is limited by its nonrandomized design and small sample sizes for some treatment groups, the authors cautioned. While data supported that patients switched drugs for efficacy reasons, there may be other reasons, including geographic differences in logging adverse events.

Follow-up guidelines also differed among drugs, they noted. Until 2014, two yearly visits were recommended for rituximab, natalizumab, and fingolimod, and one annual visit was recommended for injectable DMTs. This may have affected how adverse events were recorded. Since 2015, follow-up guidelines have been identical.

The limited study period reduced the ability to analyze long-term disability outcomes, the authors added. Lack of volumetric MRI data also prohibited differences in atrophy rates from being detected.

Multiple sclerosis: Cholesterol crystals prevent regeneration in central nervous system


https://speciality.medicaldialogues.in/multiple-sclerosis-cholesterol-crystals-prevent-regeneration-in-central-nervous-system/

Loss of spinal nerve fibers not the only cause of disability in multiple sclerosis


It is commonly thought that in MS, the loss of axons (nerve fibres) contributes to the chronic disability found in many patients. This has led to the wide use of MRI to measure the cross sectional area of the spinal cord in order to predict disability.

But researchers from Queen Mary University of London have now sampled spinal cords of thirteen people with MS and five healthy controls, and found that spinal cord cross sectional area is not a good predictor of axonal loss.

Lead researcher Klaus Schmierer said: “The lack of association between axonal loss and spinal cord cross sectional area significantly changes our understanding of chronic disability in MS.

“The nature of the spinal cord as a highly organised and largely autonomous network needs to be appreciated. We need to identify other factors which – over and above axonal loss – determine the collapse of the spinal cord network and lead to the functional deficits seen in MS.

“In , people with less than 10% of their  may still be able to have useful lower limb movement, but in MS, patients with as much as 40% of their axons retained, as shown in our study, are almost invariably wheelchair bound. So there is clearly something happening here which we’ve yet to understand.”

The researchers say that finding other factors that cause the chronic disability seen in MS could help identify targets for new treatments.

The team’s preliminary results indicate that the loss of synaptic connections in the MS  is substantial, and that this could be the missing link that is driving disability.

Brain-damaging vaccines, pesticides and medicines generate nearly $800 billion a year in medical revenues.


‘The current estimated annual cost for nine of the most common neurological disorders in the U.S. was a hefty $789 billion, a recent paper revealed. According to the paper, these conditions include Alzheimer’s disease and other forms of dementia, traumatic brain injury and Parkinson’s disease, as well as epilepsy, multiple sclerosis, and spinal cord injury.

get-attachment (324)

Researchers also projected that health care costs associated with brain damage will continue to increase as the number of elderly patients were expected to double between 2011 and 2050. Data showed that medical costs related to dementia and stroke alone were estimated to be more than $600 billion by 2030.

“The findings of this report are a wake-up call for the nation, as we are facing an already incredible financial burden that is going to rapidly worsen in the coming years. Although society continues to reap the benefits of the dramatic research investments in heart disease and cancer over the last few decades, similar levels of investment are required to fund neuroscience research focused on curing devastating neurological diseases such as stroke and Alzheimer’s, both to help our patients and also to avoid costs so large they could destabilize the entire health care system and the national economy,” said lead author Dr. Clifton Gooch, ScienceDaily.com reports.’

Source:www.davidicke.com

MS Clues Found in Blood


Serum microRNAs may serve as biomarkers for multiple sclerosis

MicroRNAs are small RNA molecules that influence basic cellular processes and have been proposed as biomarkers for the diagnosis, progression and treatment of multiple sclerosis.

In a new study conducted at the Ann Romney Center for Neurologic Diseases at Brigham and Women’s Hospital, Harvard Medical School researchers have found that serum microRNAs are linked to MRI findings in the brain and spinal cord in patients with MS.

These findings suggest that microRNAs could serve as promising biomarkers for monitoring the progression of MS and could help to identify distinct underlying disease processes, such as inflammation and tissue destruction.

The research was published on Jan. 23 in JAMA Neurology.

In a large study, researchers examined the connection between serum microRNAs and MRI measures taken to evaluate the severity of patients’ MS, which included looking at lesions and atrophy, a measure of degeneration of the cells in the central nervous system. The researchers found that the expression of certain microRNAs was linked to the MRI measures.

These associations, the study suggests, could be protective or harmful to patients (depending upon the function of the microRNA). They also found that different mechanisms were linked to different locations of MS changes, such as in the brain or spinal cord. Additionally, the study suggested certain sets of microRNAs were linked to lesions, while others were linked to atrophy, which is known to have more devastating effects.

“These findings tell us the disease is heterogeneous. There’s a complex set of mechanisms at play, and it may vary from patient to patient,” said senior co-author Rohit Bakshi, the HMS Jack, Sadie and David Breakstone Professor of Neurology at Brigham and Women’s. “Another implication of this research is that it could eventually lead to us having a blood test to identify the subtype of MS in a patient, to help guide therapeutic decisions and prognosis,” said Bakshi, who is also HMS professor of radiology at Brigham and Women’s.

“MicroRNAs could serve as biomarkers of the underlying MS disease processes, once validated and standardized for clinical settings. In addition, these markers have the potential to provide novel treatment targets,” said Roopali Gandhi, senior co-author and HMS assistant professor of neurology at Brigham and Women’s.

Multiple Sclerosis Clues Found in Blood.


MicroRNAs are small RNA molecules that influence basic cellular processes and have been proposed as biomarkers for the diagnosis, progression and treatment of multiple sclerosis.

In a new study conducted at the Ann Romney Center for Neurologic Diseases at Brigham and Women’s Hospital, Harvard Medical School researchers have found that serum microRNAs are linked to MRI findings in the brain and spinal cord in patients with MS.

These findings suggest that microRNAs could serve as promising biomarkers for monitoring the progression of MS and could help to identify distinct underlying disease processes, such as inflammation and tissue destruction.

The research was published on Jan. 23 in JAMA Neurology.

In a large study, researchers examined the connection between serum microRNAs and MRI measures taken to evaluate the severity of patients’ MS, which included looking at lesions and atrophy, a measure of degeneration of the cells in the central nervous system. The researchers found that the expression of certain microRNAs was linked to the MRI measures.

These associations, the study suggests, could be protective or harmful to patients (depending upon the function of the microRNA). They also found that different mechanisms were linked to different locations of MS changes, such as in the brain or spinal cord. Additionally, the study suggested certain sets of microRNAs were linked to lesions, while others were linked to atrophy, which is known to have more devastating effects.

“These findings tell us the disease is heterogeneous. There’s a complex set of mechanisms at play, and it may vary from patient to patient,” said senior co-author Rohit Bakshi, the HMS Jack, Sadie and David Breakstone Professor of Neurology at Brigham and Women’s. “Another implication of this research is that it could eventually lead to us having a blood test to identify the subtype of MS in a patient, to help guide therapeutic decisions and prognosis,” said Bakshi, who is also HMS professor of radiology at Brigham and Women’s.

“MicroRNAs could serve as biomarkers of the underlying MS disease processes, once validated and standardized for clinical settings. In addition, these markers have the potential to provide novel treatment targets,” said Roopali Gandhi, senior co-author and HMS assistant professor of neurology at Brigham and Women’s.