Medical Practice

Understanding the practical aspects of cannabidiol (CBD) and tetrahydrocannabinol (THC)

 

Virginia Thornley, M.D., Board-certified Neurologist, Epileptologist

@VThornleyMD

July 15, 2018

Introduction 

This serves as medical information for educational purposes only not medical advice. Please consult with your treating  physician.

In contrast to the rest of the blog which is more scientific, this gives more practical information in the day to day workings of recommending medical cannabis. It gives the behind the scenes processes that happens before a patient can even begin to start their medical product. It is not a magic pill but because it is unlawful in Florida, a physician cannot even write it on a prescription pad. It takes one hour or more to evaluate, counsel and go over the registration process when presenting for the first time to a doctor.

For more detailed information and scientific references for specific indications please refer to
https://neurologybuzz.com/

Medical cannabis is one of the most misunderstood and controversial medications in the world. Long suppressed for over a century, it is one of the most misunderstood medications known to mankind despite being used for thousands of years with medical intent.

 

This is to give a brief basic background of mechanisms, rationale for ratios, combinations, pitfalls of isolates and synthetics and legal implications.

Background

Very briefly, the endocannabinoid system is found naturally in our body. It is responsible for the runner’s high people get. It gives a sense of wellbeing, not endorphins like most people think, those molecules are too large to pass the blood brain barrier. There are 2 receptors:(1) the CB1 receptor found mostly in the nervous system and (2) the CB2 receptor which is more abundantly found in the immune system. Anandamide works on the CB1 receptor, Tetrahydrocannabinol (THC) is similar to this and works on the CB1 receptor. CBD or cannabidiol is from the cannabis sativa plant and is also a cannabinoid. One needs 100 times CBD to get the same euphoria as THC. CBD is not intoxicating, legal and works on a wide variety of symptoms including pain, seizures and anxiety. CBD is similar to 2-arachidonoyl glycerol which is a natural cannabinoid. When you combine the 2 together, CBD will offset side effects of THC including paranoia, hyperactivity and agitation. This is a little known fact to those who self medicate.https://neurologybuzz.com/2018/04/02/medical-marijuana-vlog-series-part-i-mechanisms-medical-benefits-of-non-intoxicating-cannabidiol-and-tetrahydrocannabinol/

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Pitfalls of self-medication

When patients self-medicate and use pure THC to alleviate symptoms, there are intoxicating effects which are not seen when recommended medically using oral forms, cream or patch. At low doses, as is done when recommended medically, THC is non-euphoric. When THC is combined with CBD the side effects of THC are offset. The dangers of patients who self-medicate is that they do not know where the products are coming from and it can be mixed with potentially dangerous substances that can be potentially fatal. In addition, there are highly potent synthetic illegal cannabinoids known as K2 and spice which at high doses can cause cardiotoxicity and fatalities. https://neurologybuzz.com/2018/05/31/the-fatal-effects-and-mechanisms-of-synthetic-cannabinoids-including-jwh-compounds-used-recreationally/

Why is a CBD and THC combination important?

In regulated licensed dispensaries, CBD is combined to offset the side effects of THC making it better tolerated. This concept is not well-known to the public or the medical community. The stigma is still strong. THC is not recommended by itself because of side effects including paranoia, agitation and hyperactivity. Within the nursery farm, the strains of the cannabis sativa plants are grown at a certain temperature under a certain amount of sunlight. It is strictly controlled so that different strains are produced.

 

CBD by itself

With pure CBD, there are certain medical symptoms that are alleviated better than combination CBD:THC.

It is legal. There are many companies with CBD products but it is difficult to know how pure these products are, even if you have a small amount of hemp it can be marketed as CBD hence, its ineffectiveness. Some of the most effective CBD products can be found from Colorado and California, just anecdotally. Everything else will be hit or miss.

In the state of Florida, there are very few medically beneficial CBD products, it’s trial and error. The purer the form such as full spectrum CBD oil the more expensive it will be because processing organic products are costly. A cheap product will likely not be as pure just because of the huge amount of work that goes into extracting the cannabidiol. In addition, some may have flavors, cutting agents and other agents to dilute it but because it’s unregulated it is not disclosed.

Ratios

CBD alone has no psychoactivity but medical value. CBD must be combined with THC in order to offset its side effects of paranoia, agitation and hyperactivity. The lowest ratio is 1:1 ratio which covers a wide variety of symptoms. The ratios increase incrementally 1:4, 1:9, 1:20, 1:80, 1:90. The higher ratios are reserved for the terminally ill as it can cause greater amounts of side effects. Higher ratios of THC achieves greater pain relief. Higher ratios of CBD help with anxiety but can also help with pain and seizures. Dosages and ratios should be low then increased incrementally by the week to see the best effect. https://neurologybuzz.com/2018/04/04/part-iii-medical-marijuana-video-series-vlog-different-combinations-and-ratios-of-cannabidiol-and-tetrahydrocannabinol-and-indications/

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Time of onset and duration

There are different ways of trying it: vaporizer lasts 1 hour and takes about 10 minutes to get into your system. Because the vaporizer is inhaled into the lungs the onset is the fastest because of the rich supply of blood vessels in the lungs. It is advisable to try the vaporizer at home or at night before setting out to see how it affects you. Oral forms last 6 to 7 hours and takes about 1/2 hour to get into your system. Oral form comes in oil concentrate and tincture. Cream and patch last about 12 hours or longer depending on the preparation. Medical marijuana is NOT recommended by physicians to be smoked. Recreational marijuana by smoking is prohibited and unlawful in Florida. This law varies by state. When different parts of the plant are taken together including the terpenes it gives an entourage effect which is more medically valuable than when components are isolated for its use.https://youtu.be/Ir4rwgF2iNc

Are there any edibles in Florida?

As of July 2018, there are no edibles in the state of Florida. It will take an enormous amount of applying, submitting documentation and providing capital before edibles will be implemented in Florida. The dispensaries are working on this.

 

Registration process: what to expect in Florida

The process includes an evaluation by a qualified licensed physician. https://neurologybuzz.com/2018/07/12/legalities-and-application-process-in-the-state-of-florida/A qualified physician undergoes a 2-hour course and holds a full medical license in the state of Florida. One is evaluated and if  patient meets the stringent criteria, they obtain a registry number. The patient will undergo a registration process which takes between 2-4 weeks. An email arrives before the card then one is instructed to call the office so that recommendations are placed in the system. Oftentimes, if you don’t hear back in 4 weeks it is advisable to give the registry a call. It may be a misenetering of an e-mail causing a hold-up.

Regulated dispensaries in the Florida

In Florida state there are 13 medical marijuana treatment centers and 43 retail dispensaries as of July 2018. In the state of Florida, patients can only obtain the Cannabis products recommended from their treating physicians from these dispensaries. It is illegal to smoke. There are 4 ways of taking it: oral, vaporizer, cream and patch. It is advisable to visit one of the licensed dispensaries in person so that the exact instructions can be given. Physicians recommend orders which are entered into the system. So long as the product is within the number of mg dispensed and the way it is recommended (oral, vaporizer, cream or patch) patients are at the liberty to change the ratio or dosage so long as it is within the orders.

 

Once you are registered

An e-mail with the marijuana card number comes before the physical card. It is advisable to call the physician office so the orders are placed then physically visit the dispensary of your choice so specific instructions can be taken. Because this is not a pharmacy, doctors do not have immediate access to the dispensary. One should be aware of which product they are taking before their next checkup. This can be easily accessed through the website of the dispensary.

The orders will expire after 70 days after which there is a processing fee of renewal at our office. The certification for medical marijuana expires after 1 year. One must be re-evaluated by their physician before then.

CBD is purely cannabidiol, it is non-psychoactive and legal. THC at low doses is non-intoxicating. Dispensaries combine CBD and THC to offset side effects.  It is federally illegal. It is advisable to be registered under a medical doctor who is qualified to determine if one meets criteria. Medical cannabis products can only be dispensed from a regulated licensed dispensary. Medical marijuana products outside of the jurisdiction of Florida regulates licensed dispensaries cannot be advocated.

Legal implications of THC

In some states, such as Florida, medical use of cannabis is recognized. THC is still considered federally illegal. Recreational use of cannabis is illegal. Smoking THC is illegal. Physicians cannot prescribe it since it is a schedule 1 drug but can recommend it. Schedule 1 drugs are considered illicit and labeled as having no medical use.

In other states, medical and recreational use is allowed.

In other states, medical and recreational use is completely banned.

The law also varies regarding cultivation of the cannabis sativa plant.

Countries will vary in their marijuana laws.

The laws change very rapidly. Regulations are changed nearly every month with more documentation required from physician offices including consent, doctors’ notes, patient information with indication. As each month goes by another new document is required for submission from the physician office. There is increasing bureaucracy likely signifying resistance at some upper levels against its use related to economic and political reasons. Dispensaries have an equally challenging time. Even worse are small farms applying for licenses huge amounts of capital and documents are required.

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Legal implications of CBD

CBD is legal throughout the US. Countries may vary in their laws since they both come from the cannabis sativa plant.

FDA approved medications and products approved in Europe with CBD and THC

A medication called Epidiolex for seizures with CBD has recently been approved for seizures. Because it comes from a strain from the cannabis sativa plant, cannabis will need to be deregulated from the schedule I category before Epidiolex can be marketed to the public.

Dronabinol has long been approved for nausea and can only prescribed for patients with cancer with chemotherapy induced nausea. It is a synthetic THC and is FDA approved.

In Europe, the medication Sativex which is a combination of CBD:THC has long been used for spasms in multiple sclerosis. This is not available in the US.

In summary

For patients, it is beneficial to have a working understanding of the different strains, different forms that are available in order to obtain the best benefit.  Dispensaries have a huge breadth of products. It is easier to understand as much as possible before facing the overwhelming number of options. Patients must understand all the legal implications in your state as they change rapidly. It is not only a medication it is affected by state and federal laws that change in a blink of an eye which can affect the patient if they are not aware.

For doctors recommending, one must be well-versed in understanding the ratios, the combinations, the potential side effects, drug interactions, the latest scientific research since these are the only guidelines that are guiding us from a scientific level. Pre-clinical studies cannot be ignored nor studies on synthetics to have a better grasp of understanding how it works. One must have a basic understanding in the relationship of the different strains, effects on each other, entourage and synergistic effects of the phytocannabinoids taken in combination and not in isolation. Patients come with complex medical problems it is always prudent to do due diligence in understanding as much as possible before recommending a product that was never studied for medical purposes in medical school. Patients will ask tough questions, physicians should understand as much as possible and do their homework being up to date on legislations as well as the most recent research.

One must also follow the legal implications, current regulations which are frequently updated. It is the physician’s responsibility to understand the mechanisms, be up to date on the literature because this is a pioneering science. Those recommending right now are trailblazing and should still be mindful of the great role you play in understanding what literature is available and to read voraciously.

Last thoughts

While much is still unknown about CBD, THC and mechanisms, there is great anecdotal data from history and clinical anecdotal experience supporting its benefits. While many traditionally trained physicians scoff at the prospect of introducing alternative treatments, one must bear in mind cannabis was not an alternative medication before it was banned in 1830.

While scientists are working overtime in elucidating the mechanisms to combat diseases such as cancer, one must bear in mind that medical cannabis is beneficial when taken in combination with other terpenes found in the plant and the components are not isolated from each other. THC works best in combination with CBD and with other components from the cannabis sativa plant.

When components are isolated from each other and products become synthetic and manufactured much of the benefits are lost and significant side effects result. https://neurologybuzz.com/2018/05/31/the-fatal-effects-and-mechanisms-of-synthetic-cannabinoids-including-jwh-compounds-used-recreationally/

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Once it becomes synthetic and components are isolated, the benefits will be substantially altered.

 

Now is a optimal time to try the benefits of medical cannabis while it is still all organic and being produced on farms and regulated for its use, unsullied by synthetic forms where the risk of side effects are greater.

While much is still to be learned, for a medicine that can easily cover 5 symptoms in one setting, it is an extraordinary time to be recommending and benefiting from medical cannabis while it is still organically natural and pure.

 

Introduction/Disclaimer

About

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fibromyalgia

Medical marijuana in fibromyalgia: molecular mechanisms and small randomized controlled trials

Virginia Thornley, M.D., Neurologist, Epileptologist

@VThornleyMD

June 17, 2018

Introduction

Fibromyalgia used to be  a condition denoting excessive pain and was previously questionable as there was no testing that could prove or disprove it. Now, the current thought is that it is attributed to hypersensitivity of the nervous system to pain impulses resulting in multiple points of pain in the body.

Endocannabinoid system in pain modulation

The endocannabinoid system is a major chemical neurotransmitter system that has only come to light as to physiology in the last 20 years. The CB1 receptor is found predominantly in the nervous system on which the endogenous endocannabinoid anandamide exerts its effects. The CB2 receptor is found mostly in the immune system on which 2-Arachidonoylglycerol acts. In the nervous system, cannabinoid receptors are seen in the periaqueductal gray area, ventromedial medulla and dorsal horn of the spinal cord which are areas where pain transmission takes place. This suggests that endocannabinoids play a major role in modulation of pain and can impact pain control through manipulation of this system.

Anandamide and and 2-Arachidonoylglycerol are synthesized on demand. It is released immediately after production. 2-AG is formed from a 2 step process. Anandamide has a low affinity to the TPRV1 receptor (2).

1,2-diacylglycerol (DAG) is  a precursor or 2-AG which is formed by hydrolysis of membrane phosphoinositides. DAG is hydrolyzed by 2-AG hydrolase to form 2-AG. 2-AG may be stimulated by activation of G protein receptor such as glutamate receptors. It activates both CB1 and CB2 receptors. Cannabidiol which is found in the cannabis sativa plant is a natural mimetic of 2-AG. Endogenous 2-AG is found 170 times more than Anandamide in the brain. Exogenous 2-AG suppresses nociceptive stimulus (2). 2-AG activity is potentiated with natural 2-acylglycerols which enhances the effects which does not happen when used alone. This is an entourage effect found in the brain where the combination of substances give a combined resulting effect which does not occur if used alone (2).

Mechanisms in pain modulation

Cannabinoids were found to reduce nociceptive transmission at the level of the pain c-fiber responses in the spinal dorsal horn.

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Randomized controlled trial in fibromyalgia

In one study of 40 patients in a randomized controlled clinical trial, nabilone which is a synthetic cannabinoid was given over a 4 week period. Measures that were evaluated included the visual analog scale for primary outcome and for secondary outcome measure, tender points, secondary outcome measure, Fibromyalgia Impact Questionnaire (FIQ) at weeks 2 and 4 were used. There was statistical difference in treated vs. control groups for pain (P value< 0.02), anxiety (P<0.02 and FIQ (P<0.02). There were more side effects for the treated cohort compared tot he placebo controlled group. This study demonstrates that cannabinoids may be an effective treatment for fibromyalgia (1).

In one paper that reviewed 18 randomized controlled clinical trials of cannabinoids in chronic pain syndromes including fibromyalgia, cannabinoids were found to be an effective type of treatment. Despite the short duration of the trials, pain relief was effective and mild to moderate adverse effects were noted. Larger clinical trials are needed (2).

About

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https://neurologybuzz.com/

  1. Skrabek, et al, “Nabilone for the treatment of pain in fibromyalgia,” J. Pain, 2008, Feb., (9)2:164:173
  2. Lynch, et al, “Cannabinoids for treatment of chronic non-cancer pain: a systemic review of randomized trials,” Br. J. Pharmacology, 2011, Nov., 72(5):735-744
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Tourette's Syndrome

Medical cannabis in Tourette’s syndrome: case reports and a small randomized controlled clinical trial

Virginia Thornley, M.D., Neurologist, Epileptologist
June 11, 2018

@VThornleyMD

Introduction
When one hears Tourette’s syndrome the glorified Hollywood impression young person who shouts obscenities comes to mind. It is composed of complex motor or vocal tics generally preceded by a premonitory urge. Vocal tics may consist of coprolalia and echolalia. Motor tics may involve complex actions including copropraxia or simple motor tics. Obsessive compulsive disorder and other neuropsychiatric conditions are often associated with it.

The underlying problem is thought to be related to an imbalance of the neurotransmitters necessary to maintain the fine coordination necessary to avoid excessive motor activity. When that balance is impaired there is less inhibition of motor loop control resulting in reverberating loops and excess movements involving motor groups including muscles controlling speech and body movements. Because the pathophysiology is not entirely clear, these may be some of the most challenging neurological disorders in terms of treatments from a neurological standpoint.

Background on Cannabinoid Mechanisms
With the advent of medical cannabis used in neurological conditions, new indications are discovered. The mechanism is at the level of the endocannabinoid system already inherent within the system. There are 2 receptors, CB1 and CB2. The CB1 receptor is found mostly within the nervous system. The CB2 receptor is mostly in the immune system but is found in other organ systems to a lesser extent. Tetrahydrocannabinol (THC) is a mimetic of Anandamide which works within the endocannabinoid system and has medical properties. THC interacts with the CB1 receptor which is responsible for psychoactive properties most people are familiar with. It is likely at the CB1 receptor where other neurological symptoms are alleviated since this most abundantly found in the nervous system and many neurological symptoms are ameliorated with medical cannabis. Cannabidiol (CBD), which is non-psychoactive, is a pharmacomimetic of 2-AG or diarachidonylglycerol. It is an non-competitive allosteric modulator of the CB1 receptor which alleviates any side effects from THC when they are combined together (1).

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Clinical Reports
There is one report of a patient treated with nabiximol where there was improvement of tics. There was overall improvement in quality of life and global improvement. There was lessening of premonitory urges. Patients feel the premonitory symptoms are more bothersome. In one study anti-psychotics helped ameliorate the motor tics but did not improve the premonitory symptoms (2). Nabiximol was used in this study where 1 puff contained 2.7mg of THC and 2.5mg of CBD. Assessments included the Yale Global Tic Severity Scale (YGTSS), Tourette’s Syndrome Symptom LIst (TSSL), Modified Rush Video Tic Scale, Premonitory Urge for Tic Scale, Global Clinical Impairment, Visual Analogue Scale for satisfaction for the GTS-Quality of Life. The study showed the best results in the quality of life in terms of alleviating premonitory urges. Larger clinical trials are needed to further this study (2).

In a recent case report, THC (trademark Sativex) was used with success to treat a patient using 10.8mg THC and 10mg CBD daily. Yale Global Tic Severity Scale (YGTSS) and the Original Rush Video Tic Scale were used as measures of evaluation. The results demonstrated effective use of THC in combination with THC for treatment in medically refractory patients (5).

In one single dose, cross over study in 12 patients and a randomized trial in 24 patients spanning 6 weeks was performed (3). The study demonstrated that THC reduces tics without any disruption in cognitive function. Neuropsychological impairment was not seen (3).

In the randomized double blinded placebo-controlled clinical trial of 24 patients, THC of up to 10mg was used in the treated cohort over 6 weeks. Measures used included the Tourette’s Syndrome Clinical Global Impression Scale (TS-CGI), Shapiro Tourette Syndrome Severity Scale (STSS), the Yale Global Tic Severity Scale (YGTSS), Tourette Syndrome Symptom List (TSSL) and the videotape based rating scale. Patients were rated at visits 1 for baseline, visits 3-4 during treatment and visits 5-6 after withdrawal. There was a significant difference between both groups. There was a significant reduction in motor tics, vocal tics and obsessive compulsive disorder. No significant adverse cognitive effects were noted (4).

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More randomized controlled clinical studies are necessary
While there may be a paucity of large clinical trials of the use of medical cannabis in Tourette’s syndrome, tetrahydrocannabinol is a potential therapeutic agent in a neurological disorder where treatment options are very limited and often times unsuccessful. Adverse side effects can preclude treatment using conventional pharmaceutic agents.

While large randomized controlled clinical trials are necessary in providing standard of care, tetrahydrocannabinol has emerged as a potential treatment option used by clinicians who are on the frontlines of treating this debilitating disorder.

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Reference
1. Laprairie, et al, “Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor,” Br. J. Pharmacology, 2015, Oct., 172(20):4790-4805
2. Kanaan, et al, “Significant tic reduction in an otherwise treatment-resistant patient with Gilles de la Tourette syndrome following treatment with nabiximol,: Brain Science, 2017, Apr., 7 (5):47
3. Muller-Vahl,”Cannabinoids reduce symptoms of Tourette’s syndrome,” Expert Opin Pharmacother., 2003, Oct., 4(10):17-1725
4. Muller-Vahl, “Delta-9-Tetrahydrocannabinol (THC) is effective in the treatment of tics in Tourette syndrome: a 6 week randomized trial,” J. Clin Psychiatry, 2003, Apr., 64 (4):459-65
5. Trainor, “Severe motor and vocal tics controlled with Sativex®,” Australas Psychiatry, 2016, Dec, 24 (6):541-544

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stem cell

Mesenchymal stem cell therapy: a viable non-surgical option in lower back pain treatment

Virginia Thornley, M.D., Neurologist, Epileptologist

June 9, 2018

Introduction

Back pain is one of the most common pain disorders encountered by neurologists, neurosurgeons, orthopedic surgeons and pain specialists in the out-patient setting. It is not uncommon for patients to go through an extensive list of medications, steroid injections, physical therapy and even surgery and still remain in unrelenting pain. There is a growing interest in alternative treatments especially with the opioid crisis looming and restriction of strong pain medications. This seeks to review scientific mechanisms behind the success in stem cell treatment. It recaps clinical data. Despite a scarcity of published huge randomized clinical trials, there is a growing and clamoring need for alternative treatments such as stem cell therapy for patients desperately trying to find alleviation from their pain. Trailblazing physicians are using this treatment option in real life practice with growing results.
Back pain is a very common disorder which is especially prevalent in the elderly after wear and tear of long-term activity in conjunction with the natural degenerative changes that come with the aging process. Normally the intervertebral disc complex can withstand compression and shear forces because of the proteoglycans that bind water molecules. This becomes lost with aging. In degenerative disc disease, there are pro-inflammatory molecules.

Pathogenesis of degenerative disc disease
Within the nucleus pulposus, there is no vascular supply except at the end neural plate, has no nerves and is prone to damage. The nucleus pulposus relies on glycolysis for effective disposal of waste products through the endplates. After decades, the nucleus pulposus no longer has notochordal features and is replaced by small chondrocyte like cells. There is replacement of the collagen type 1 and collagen type 2 loss eventually replaced with fibrocartilaginous material. Eventually with time, the endplates have calcification of the small pores where molecules diffuse (1).

 

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There are anabolic processes involved as well as catabolic processes including involvement of enzymes, inflammatory mediators, proteinases, aggrecanases. Examples include IL-1 and TNF-alpha. because the disc is avascular this creates an environement of poor regenerative responses with harsh conditions (3).

Some patients may have a genetic predisposition to have flawed extracellular matrix where degenerative disc disease may occur more severely than in other people. Cleavage of proteoglycan can occur with enzymes resulting in loss of height and less ability to reduce compressive and shearing forces. In addition, environmental factors including occupational activities, excessive physical activity impacting the spine may contribute towards degenerative disc disease (1).

Alternative treatment: stem cell therapy
In order to address these issues, various treatments have arisen to try to try to halt the cascade leading to degenerative disc disease. This includes implantation of biomolecules to reduce the catabolic process.

 

 

Stem cell research is gaining more traction as a viable alternative for treatment of this debilitating condition. One study looked at the potential of nucleus pulposus-like cells derived from mesenchymal cells in the rabbit model. From these cells, SOX9, ACAN, COL2, FOXF1, and KRT19 genes were expressed(2). Transplanted nucleus pulposus cells were integrated into the intervertebral disc complex. Improved water content, glycosaminoglycan, and cellularity within the complex was noted. There was a suggestion of biosynthesis with the gene expression of SOX9, ACAn, COL4 (2). This animal study demonstrates that there may be value in nucleus pulposus cells derived from mesenchymal cells may lead to clinical studies where stem cells can be used for back pain.

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Injection of mesenchymal stem cells
Injections of mesenchymal stems cells into the disc may reduce the clinical pain and restore disc tissue loss. It may be able to reduce the catabolic microenvirnment (3)

Clinical studies of stem cell use in humans
It appears that stems cells of mesenchymal type derived from adipose or the umbilicus may have the most promise (4).

In one small study of 10 patients, autologous bone marrow mesenchymal cells were were injected in the nucleosus pulposus and followed for a year. After 3 months, there was improvement of pain and disability of 85% of the maximum. After 12 months, there was still high water content within the nucleosus pulposus (5).

Stem cell effects were studied in 2 patients with back pain and leg numbness. Marrow fluid was obtained autologously from the ilium from each patient. Mesenchymal stem cells were cultured in autogenous serum. Fenestration was performed and collagen sponge was applied percutaneously to the affected intervertebral disc complex. After 2 years, the T2 signal was high showing increased disc content in the grafted discs. Clinical symptoms were ameliorated (6).

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Clinical trials
In an open label trial of 26 patients, using the VAS and Oswestbry disability scale, there was reduced pain after percutaneous injection of bone marrow cell concentrate showing autologous mesenchymal stem cells are a viable alternative treatment for back pain (7). They studied the patients through 12 months. Those who received >2000 colony forming fibroblast units/ml had faster and greater pain reduction.

There is one small randomized controlled clinical trial in 24 patients using the Pfirrmann grading scale for degeneration, allogeneic mesenchymal cells were transferred to the clinical cohort. Significant relief of pain was noted compared to the sham group demonstrating that allogeneic transfer may be logistically better than autogenous transfer (8).

 

Possible adverse effects
Concerns include transformation into neoplastic process. This seems to be true with embryonic stem cells which are much earlier seen in the cell lineage. Mesenchymal cells are further down the line as a committed cell type to obviate this. With in vitro culturing, there is concern for cell mutations, but this is less of a concern if it is a same day procedure, autologous and exist as when they were in the body previously. There is concern for extravasation beyond the limit of the disc and if combined with other treatments such as PRP it may promote osteogenesis. In addition, animal models may not replicate the harsh microenvironments of disc pathology where continual torsion and pressure is involved and effects and outcomes might be different (3).

In summary
There is much scientific and animal model data that stem cells remain a viable option for treatment of back pain which is one of the most common problem encountered by neurologists, neurosurgeons, orthopedic surgeons and pain management specialists. While there is much demonstrated in animal studies, clinical trials are still very sparse. This treatment, however, shows promise and despite paucity of clinical trial data, this treatment is gaining traction in practicing clinicians who treat back pain.

Given the failure with medications and even with surgery there is increased interest in alternative treatments including stem cell therapy.

Introduction/Disclaimer

Introduction/Disclaimer

References

1. Rosenberg, et al, “Bedside to bench and back to bedside: translational implications of targeted intervertebral disc therapeutics,” J. Orthop. Translat., 2017, Apr., 10:18-27.
2. Perez-Cruet, et al, “Potential of human nucleus pulposus-like cells derived from umbilical cord to treat degenerative disc disease,” Neurosurgery, 2018, Feb., doi:10.1093/neuros/nyy012
3. Zeckser, et al, “Multipotent stem cell treatment for discogenic low back pain and disc degeneration,” Stem Cell Int., 2016, doi: 10.1155/2016/3908389
4. Knezevic, et al, “Treatment of chronic low back pain – new approaches on the horizon,” J. Pain Res., 2017, May 10, 10:1111-1123
5. Orozco, et al, “Intervertebral dis repair by autologous mesenchymal bone marrow cells: a pilot study,” Transplantation, 2011, Oct., 15, 92 (7):822-8
6. Yoshikawa, et al, “Disc regeneration therapy using marrow mesenchymal cell transplantation: a report of 2 cases,” Spine, 2010, May 15, 35 (11):E475-80
7. Pettiness, et al, “Percutaneous bone cell concentrate reduces discigenic lumbar pain through 12 months,” Stem Cell, 2015, 33(1):146-156
8. Noriega, et al, “Intervertebral disc repair by allogeneic mesenchymal bone marrow cells,” Transplantation, Aug., 2017, 101(8):1945-1951.

 

 

 

 

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Medical Practice

Returning to the sacred patient-physician relationship

Virginia Thornley, M.D., Neurologist, Epileptologist

@VThornleyMD
https://neurologybuzz.com/

June 6, 2018

Introduction

Seeing physician burnout articles every page you swipe on social media, on physician online media groups, and in editorials of national syndicates are becoming the norm. Not to minimize it, it can become fairly discouraging reading about the fate of well-educated healers with only the noblest intentions becoming victims of the healthcare climate that is medicine today. Reading about these issues, one can become disengaged when you are in the throes of working.  It is when one becomes completely removed from the situation when you realize the extent of the dysfunctional system. Yes, the system is terrible, yes, there are too many regulations, too many middlemen, too many people getting in the way of the genuine whole-hearted connection between patient and physician. Where does that leave us and how can we rectify the situation?

Patient-physician relationship: the sacred relationship

It used to be that the relationship was between patient and physician. Patient and physician. There was no such thing as health insurances, no such thing as MOC, no such thing as EMR, no such thing as healthcare professionals. It was patient and physician. Physician and patient. Doctor and patient. Patient and doctor.

There was nothing to separate the physician from caring for his patients. Doctors used to travel with their doctor’s bags to their patient’s home, making house calls, being paid with services or what little the family had on their farms. Doctors took out their trusty stethoscopes and gave a healing balm, sometimes they helped their patients sometimes not, since the remedy was beyond the technology at the time. There was no such thing as malpractice insurance. No such thing as deductibles, no such thing as premiums, no such thing as clicking little boxes that sums up a human’s suffering. The relationship between a doctor and his patient was at its best and humblest-to care for the sick. Not to cure, not to treat but to comfort always. Absolutely nothing stood in the way between doctor and patient. That relationship was pure and untouched.

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Going back to your roots, back to the patient-physician relationship

How does one go back to this very sacred traditional relationship? If doctors do not realize this is a crisis situation where this very symbolic connection is being threatened by a huge number of many outside forces, they must be hiding under a rock. When one sees hundreds of articles on physician burnout, how to end the patient interview, courses on coding to get the most out of a visit, you know there is something utterly amiss with the system.  There will be the business end of the situation, you do have to pay for staff salaries, paper supplies etc, after all. But the physician-patient relationship is one of the most paramount human connections that cannot and should not be replaced. To heal and to comfort someone during their last few days, to determine if someone no longer has meaningful recovery after suffering from a massive myocardial infarct, to tell a patient they have a glioblastoma multiforme and there is very little chance of recovery, these are sensitive dealings that should not lay on an artificial robot, a medical substitute or a paramedical person. Important discussions like these should be with the physician. In order to have these important discussions, one must first have a relationship. One must never forget why we have entered medicine, to serve our patients. The human connection between a patient and physician is one of trust and hope. But how do we get back there when there are so many compelling factors threatening its very existence?

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Acknowledge there is a problem

A basic tenet of remedying a situation is to acknowledge that there is a problem. When one realizes the way one operates is not sustainable, your psyche will address the situation and make changes. If one stays in the limbo, the system can consume you and spit you out. Such are the sad cases of colleagues ruthlessly cut to be replaced with cheap labor by the upper business echelons.  Difficulties coping with this new unsatisfying overburdensome system leads to disillusioned physicians, who previously took pride in their work now reduced to electric circuits, cogs in a machine. And because physicians are perfectionists we feel like failures if we cannot cope. This leads to the worst case scenario which is to take your own life.

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We should find pride and satisfaction in what we do. Instead, there are now wellness programs which are a slap in the face placing the blame entirely on the physicians’ shoulders because we are unable to cope. Patients cannot fathom the extent of this medical crisis. All they know is that their physicians keep getting changed because of rapid turnover or a whole encounter is all of 10 minutes to summarize 10 complex problems. The answer lies within ourselves. Nobody can turnaround the situation except ourselves. If we want change we change our whole outlook, whole way of thinking and whole way of practice, it begins within ourselves.

Get rid of the middleman

I used to have a wonderful medical assistant, she did all the pre-questionnaires for me and dutifully entered it into the computer database. As the patient entered my office, I am guilty of saying,”hold on, let me read what my assistant typed” while the patient is seated, gob-smacked, looking at me silently. Looking back I can only shake my head and wonder,”wow, what was I thinking I sound like a cold robot,” which I was. All the boxes were checked perfectly, I did my neurological exam, whipped out my pad, scribbling 5 medications for 5 different symptoms, filled out MRI forms, went over the plan speaking as quickly as possible. Off my patient went on his merry old way, disillusioned and somehow left unfulfilled. Imagine this occurring 20 times a day. I was fried by the end of the day, my patients left dissatisfied and staff went through the office like hotel guests through revolving doors because of the tediousness that is medicine today. When I used to work in hospitals, residents did the pre-work-up as was part of their training, relationships were fleeting, care was in teams and rotations.

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Now, I see new patients for 1 hour, they are now eloquent, unique stories again, not templates that you copy and paste and change with a few details according to the patient. I let them expound until they have nothing left to say. I ask my part, perform my examination which is where the healing touch occurs that every patient subconsciously craves and we go over the plan. I answer all questions until there are no more. It is not uncommon for a patient to shake my hand heartfelt looking me in the eye thanking me. Other times, I receive a warm hug. It is not just as a courtesy gesture but a real expression of appreciation. While I did not cure them I provided so much more, the therapeutic healing relationship that exists between a patient and a doctor that no matter what happens I am now there for them. My heart warms and I modestly reply I didn’t do anything. But deep down I can feel the palpable difference. I have returned to the roots of medicine. I finally understand that this is what it is all about. I now listen to them. I listen to their own unique stories. I make eye contact and take in everything they have to say, the furrowing of their brows, the tone of their voices and I hear what they are saying. I now get comments how they are happy they found me their last doctor only took 5 minutes, while I muse to myself, I used to be that doctor. I remain neutral and non-judgmental, but I am now aware there is a simply better way of practicing now.

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How does one return to your roots

Going back to the basics of communication, human connection, one remembers the reason why you entered medicine. We are slowly replaced by parallel industries where practitioners of dubious training are hailed new miracle healers. Everybody is calling themselves doctors. They spend more time listening and are less regulated. We have lost the art of listening. It has gotten lost in the world of electronic recording, the need to generate copious amounts of data on one patient encounter, in the new team service approach. The unique relationship between doctor and patient is subsequently insidiously altered-soon to be extinct as doctors are slowly being replaced and encroached by other forces. But the solution is very simple, we must return to the country doctor model. Within the very listening provides great comfort. When comfort is achieved we have done our job. We may not cure or treat, but we always comfort. The paradigm shifts back to doctor and patient.

One more time cut out the middleman

I cannot emphasize it enough, cut out the middleman. Anything that keeps you apart from your patient widens the chasm and becomes a barrier, an impediment. Assistants, insurances, computers, physician extenders, these were never around before. When you strip it back down to the bare bones, you return to the rawest, purest form of medicine-the relationship between doctor and patient. Patient and doctor. We should go back to the country doctor model.

It is only then you will realize the depth that is medicine. Only then can we practice medicine the way it is supposed to be…between physician and patient. Patient and physician.

About

https://neurologybuzz.com/

Dr. Virginia Thornley is a Board-Certified Neurologist subspecializing in Epilepsy and Clinical Neurophysiology in private practice. You can follow her on @VThornleyMD. To read more of her writings, visit https://neurologybuzz.com/

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Epilepsy

The effects of barometric pressure changes and other climate factors on the frequency of seizures

Virginia Thornley, M.D., Neurologist, Epileptologist

June 3, 2018

Introduction

It is not common for a patient to complain of seizures seeming to increase immediately before a hurricane or a big storm. Do these changes truly correlate with outside environmental factors? This article seeks to review the literature to determine the cause and mechanisms of how weather risk factors might affect epilepsy and frequency of seizures.  There is a paucity of information of barometric effects and weather changes on exacerbation of seizure frequency.

Changes in atmospheric pressure correlated with seizures 

Atmospheric pressure is defined as the weight of the atmosphere. At sea level, it is 101,325 pascals, 14.5969 pounds/square inch or 1013.3 millibars. It is also referred to as barometric pressure.

In one article studying 191 patients, with an increase in atmospheric pressure variability, seizures were noted to increase. The atmospheric pressure was obtained from metropolitan weather stations in Seattle. The maximum, minimum and changes were correlated with the number of seizures being monitored in a telemetry unit over 2005-2006. Patients with known epilepsy had an odds ratio of 2.6 (p=0.02) if the atmospheric pressure varied over 5.5mBar (1).

Higher temperatures correlated with more febrile seizures

In another study of 108,628 pediatric patients from January 2005-December, 2015 were studied regarding the effect of barometric pressure on the frequency of seizures. They were classified as febrile seizures, afebrile, epilepsy or status epilepticus. 53% presented as febrile seizures while 5.9% presented as status epilepticus. Mean atmospheric pressure was 1015.5hPa over the 11 year period. The mean temperature was 14.7 degrees Celsius with a variation of 8.3 degrees Celsius throughout the day.  The study demonstrated febrile seizures were influenced by the temperature. At lower temperatures, the emergency room visits were less while at higher temperatures the visits increased (2).

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Low barometric pressure, high air humidity increases seizures, high ambient temperature improved seizures

In another study where temperature, barometric pressure, and humidity were correlated with seizure frequency, 604 patients were studied between 2006-2010. The study showed that with a 10.7hPa lower atmospheric pressure there was an increase in seizures by 14%. Those with less severe seizures had an increase of 36%. Relative humidity of >80% correlated with increased seizures of 48%. A high ambient temperature of more than 20 degrees Celsius reduced seizures by 46% (4).

Cold temperature worsen seizures

In a study of 30 patients ages (19-54), patients with epilepsy appeared to have more active seizures during the seasons of spring, autumn and winter and less during summer of about 7%. During stable weather, it was 43% patients and unstable weather 63% had seizures. EEG’s changes occurred more frequently during winter. During winter seizures increased by 40%, in spring it increased 40% and spring by 43.3% (3).

In summary

While anecdotally, there is a correlation of exacerbation of seizure frequency to weather changes, the literature shows mixed results and some of them are small in number. One study showed a correlation of changes of more than 5.5mBar in barometric pressure leading to increased seizures frequency, another showed that it is the reduction in the atmospheric pressure itself that increased seizures. 1 study showed that high humidity may increase seizures. 2 studies showed that cold temperatures worsened seizures, while 1 study showed that higher ambient temperature worsened febrile seizures.

The data that was demonstrated is not uniform in the acquisition of information and there is a large variety of conditions. One study was primarily taken from ER visits another was information from inpatient video EEG monitoring units where the subset of patients may be completely different. In addition, there is a wide heterogeneity in etiologies of seizures which comes into play. Regardless, patients know their own symptoms, usually, if something is noted to trigger an event is it probably real.

About

Introduction/Disclaimer

https://neurologybuzz.com/

Reference

  1. Doherty, et al, “Atmospheric pressure and seizure frequency in the epileptic unit: preliminary observations,” Epilepsia, 2007, Sep., 48 (9):1764-1767.
  2. Kim, et al, “The effects of weather on pediatric seizure; a single -center retrospective study,” Sci. Total Environ. , 2017, Dec., (609):535-540.
  3. Motta, et al, “Seizure frequency and bioelectric brain activity in epileptic patients in stable and unstable atmospheric pressure and temperature in different seasons of the year–a preliminary report,” Neurol. Neurochir. Pol, 2011, Nov.-Dec., 45(6):561-566.
  4. Rakers, et al, “Weather as a risk factor for epileptic seizures: a case-crossover study,” Epilepsia, 2017, Jul., 58(7): 1297-95.
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