Archive for category Educational
Published on Apr 11, 2018
Motor learning is the understanding of acquisition and/or modification of movement.
As applied to patients, motor learning involves the reacquisition of previously learned movement skills that are lost due to pathology or sensory, motor, or cognitive impairments. This process is often referred to as recovery of function.
The three-pound organ that serves as command central for the human organism is certainly a marvel, just by virtue of the fact that the brain can appreciate its own awesomeness, even if it hasn’t quite perfected the flying car or even self-driving cars. Yet. Companies developing brain-computer interface technology are enabling humans to do things like send commands to computers by just flexing a bit of muscle. Still, there is much we don’t know about ourselves, no matter how much telepsychiatry we do. And that applies especially to medical conditions that affect the brain like epilepsy, a neurological condition for which there is no cure.
What is Epilepsy?
While most of us are probably familiar with some Hollywood-ized version of epilepsy in which someone starts flailing around after being hit by strobe lights on the disco floor, the reality is that epilepsy refers to a large group of neurological disorders that generally involve chronic, spontaneous seizures that vary greatly in how they manifest. The causes of epilepsy are also all over the place, from traumatic brain injuries and stroke to viral and bacterial infections to genetics.
It is considered a brain disorder, according to the U.S. Centers for Disease Control (CDC), though some researchers have suggested it could be classified as a neurodegenerative disease like Parkinson’s or Alzheimer’s. In fact, there is research that suggests a genetic link between epilepsy and neurodegenerative diseases.
Not surprisingly, many of the companies developing therapies for neurodegenerative diseases are also working on treatments for epilepsy and vice versa. For example, a new, well-funded joint venture involving Pfizer (PFE) and Bain Capital called Cerevel, which we profiled in our piece on Parkinson’s disease, is also in advanced clinical trials for an epileptic drug. Its GABA A positive modulator drug candidate targets GABA (Gamma-Aminobutyric Acid) neurotransmitters that block impulses between nerve cells in the brain, helping keep the nervous system chill.
Impacts of Epilepsy
More than 50 million people worldwide have epilepsy, making it one of the most common neurological diseases globally, according to the World Health Organization (WHO). The CDC estimates about 3.4 million Americans live with the condition. Globally, an estimated 2.4 million people are diagnosed with epilepsy each year. Interestingly, the disorder seems to target those who can least afford it: WHO said nearly 80% of people with epilepsy live in low- and middle-income countries.
A 2015 study of a bunch of other studies that estimated the cost of epilepsy in the United States found that epilepsy-specific costs probably average out to about $10,000 based on the variety of ranges, which means epilepsy costs the United States healthcare system about $34 billion, though the numbers are widely debated. Conversely, WHO says low-cost treatments are available, with daily medication coming as cheaply as $5 per year, so another win for the U.S. healthcare system.
Treatments for Epilepsy
There are more than 20 antiepileptic drugs used to treat epilepsy, usually to help prevent or slow the occurrence of seizures. Other therapies include surgery and electroceutical treatment in which electrical stimulation is applied, usually to the vagus nerve, the longest cranial nerve in the body. While many find relief from one or more of these options, a third of those who suffer from epilepsy are not able to manage their seizures, according to the U.S. National Institutes of Health (NIH). Below we take a look at a range of innovative therapies designed to detect, stop, or find a cure for epilepsy.
Brain Stimulation Therapies
In our article on electroceutical treatments, we highlighted a London company called LivaNova (LIVN) that offers an implantable Vagus Nerve Stimulation (VNS) therapy that has been approved by the U.S. Food and Drug Administration (FDA) to help treat those with partial seizures who do not respond to seizure medications. A medical device company with a lengthy track record of returning value to investors, Medtronic (MDT) got FDA pre-market approval last year for its Deep Brain Stimulation (DBS) therapy for use in reducing partial-onset seizure for those who have proven to not respond to three or more antiepileptic medications. DBS therapy delivers controlled electrical pulses to an area in the brain called the anterior nucleus of the thalamus, which is part of a network involved in seizures. Yet another company offering a variation of brain stimulation therapy is NeuroPace, which markets its responsive neurostimulation device, or RNS system, as “the first and only brain-responsive neurostimulation system designed to prevent epileptic seizures at their source.”
Artificial Intelligence to Detect, Predict, and Control Epilepsy
The NIH is funding further research into implantable devices that can detect, predict, and stop a seizure before it happens, “working closely with industry partners to develop pattern-recognition algorithms,” which sounds an awful lot like artificial intelligence and machine learning will be at the forefront of some future diagnostics and treatment. AI in healthcare has been an ongoing theme around here, with a recent dive into AI and mental health. Back to AI and epilepsy: A group of neurologists at the Medical University of South Carolina developed a new method based on artificial intelligence to predict which patients will see success with surgical procedures designed to stop seizures. Sounds like a great idea to learn beforehand if it’s necessary to crack open your skull.
A Boston area startup called Empatica, spun out from MIT in 2011, has raised $7.8 million for a smartwatch that detects possible seizures by monitoring subtle electrical changes across the surface of the skin. Other methods normally rely on electrical activity in the brain that tracks and records brain wave patterns called an electroencephalogram. Empatica’s seizure detection algorithm, on the other hand, can detect complex physiological patterns from electrodermal activity that is most likely to accompany a convulsive seizure. Psychology Today reportedthat the device, Embrace Watch, received FDA approval earlier this year for seizure control in children after getting the green light for the technology for adults in 2018.
AI and drug discovery for better epileptic drug candidates is yet another application that we would expect to see grow in the coming years. Silicon Valley-based startup System1 Biosciences raised $25 million last year, which included Pfizer among its dozen investors. System1 builds a sort of brain model for testing drug candidates using stem cell lines derived from patients with brain disease. The company uses robotic automation to develop these three-dimensional cerebral organoids, allowing it to generate huge datasets in a relatively short amount of time, then applying “advanced data analysis” (also AI?) to detect patterns that might match the characteristics of a neurological disease (what it refers to as deep phenotypes) such as epilepsy with novel treatments.
Cannabis for Controlling Seizures
We’ve written extensively about the suddenly booming hemp CBD market, noting that the FDA approved a CBD-based drug for epilepsy last year in our recent article on the best certified CBD oils on the market. However, we’ve only briefly profiled the company behind Epidiolex for treating rare forms of epilepsy, GW Pharmaceuticals (GWPH). Sporting a market cap just south of $5 billion, GW Pharmaceuticals has taken in about $300 million in post-IPO equity since our article, bringing total post-IPO equity funding to about $568 million. Aside from its successful epileptic drug, GW also developed the world’s first cannabis-based prescription medicine for the treatment of spasticity due to multiple sclerosis that is available in 25 countries outside the United States.
Back on the epilepsy side, Epidiolex has been approved for two rare forms of epilepsy, with clinical trials underway for two more rare neurological disorders associated with seizures – tuberous sclerosis complex and Rett syndrome. Also in the pipeline is a drug dubbed CBDV (GWP42006) that’s also for treating epileptic seizures, though the results of a trial last year were not encouraging. The same compound is also being investigated for autism. Be sure to check out our article on Charlotte’s Web, a CBD company that came about because of epilepsy.
Helping Cells Get Their Vitamin K
Neuroene Therapeutics is a small startup spun out of the Medical University of South Carolina that recently picked up $1.5 million in funding to tests its lead drug compounds, which are analogous to the naturally occurring form of vitamin K that is essential for brain health. In particular, the lab-developed vitamin K protects the integrity of the cell’s mitochondria, which serves as a sort of power plant for brain cells, helping the neural circuit fire better. Unfortunately, you can’t get the effect from simply eating a bowl of Special K each morning covered in an organic sugar substitute, so the company is developing a method to deliver the effects directly to the brain.
A Nasal Spray to Stop Seizures
Founded in 2007 near San Diego, Neurelis licenses, develops, and commercializes treatments for epilepsy and other neurological diseases. It has raised $44.8 million in disclosed funding, most coming in a $40.5 million venture round last November. The company’s flagship product is called Valtoco, a formulation that incorporates diazepam, an existing drug used to control seizures and alcohol withdrawal, with a vitamin E-based solution that is delivered using a nasal spray when a sudden seizure episode occurs. The product uses an absorption enhancement technology called Intravail developed by another San Diego area company called Aegis Therapeutics that Neurelis acquired in December last year. Neurelis submitted Valtoco to the FDA for approval in September.
While many people with epileptic conditions can control their seizures with many of the current medications or other therapies available now, there’s a big chunk of the population that is living with uncertainty. Considering the strong link between neurological disorders like epilepsy and certain neurodegenerative disorders, expect to see some good synergies in the next five to 10 years, especially as automation and advanced analytics using AI start connecting the dots between genetics, biochemistry, and brain disorders.
In 1973, UCLA computer science professor Jacques Vidal published a landmark paper, “Toward direct brain-computer communication” that both coined the term “brain-computer interface” and set the foundation for an emerging field.
“That whole concept of interacting with and sensing the brain – interpreting signals with a computer and controlling the cursor on a computer with the mind – that paper is pretty much the essence of it,” said Dejan Markovic, a professor of electrical and computer engineering and leader of the Parallel Data Architectures Laboratory. “The real question is: Can we build technologies that enable those types of things that are clinically sustainable, efficacious, and attractive to patients?”
Looking to answer that question, Markovic carries on the legacy of brain-computer interface research at the UCLA Samueli School of Engineering. For nearly a decade, he has been leading the development of a device that would be implanted in the brain to help people with a range of neurological conditions, such as anxiety, depression, or post-traumatic stress disorder. And he’s been working closely with doctors and scientists at UCLA and UC San Francisco who study the brain.
“The concepts laid out in 1973 by Vidal haven’t changed too much,” he added. “The brain and a computer can ‘talk’ to each other through electrical signals. The big thing that we are trying to change is to be able to quantify what those signals are, and affect functional networks of the brain.”
Markovic’s prototype is a small implantable device with sixty-four electrodes that fan out onto the brain’s surface. With four modules for each electrode, it constitutes a 256-channel system. The system measures tiny electric signals that tell what’s happening in the brain. The device then interprets that data, and responds with electrical pulses, which research has shown can alter mood.
In several ways, it is leaps and bounds more advanced than implants that have come before it. It’s much smaller for one. In fact it’s not immediately noticeable, unless someone’s really looking for it. It has a tiny battery than can be wirelessly charged. The device is also much more sensitive, able to detect and decipher very faint signals from the brain.
Finally, it’s a closed loop system – meaning that while still picking up the brain’s signals, it can modify the frequency and amplitude of the stimulating signal. The system brings much more data into the loop, giving doctors and scientists more information about what’s happening in real time . Other devices only deliver a constant electric signal, while this new system offers a therapy that can be more personalized to a particular patient
“Our technology could revolutionize non-pharmacological treatment of brain disorders,” Markovic said. “We want to be able to understand how various indications are expressed in the actual time waveforms, from specific points inside the brain.”
Markovic and UC San Francisco colleagues saw a major breakthrough in an experiment, which was funded by the Defense Advanced Research Projects Agency. A patient with severe anxiety was recorded before and after electrical stimulation was applied. The change in mood following stimulation was immediate and striking.
“For a person to say, ‘now I feel normal, this is me,’ that was the biggest impact point,” he said.
With a series of successful demonstrations, Markovic is now looking to commercialize the technology. This includes miniaturizing the external device down to just four cubic centimeters. But first, why go with a brain implant in the first place?
“The brain is an electrochemical organ and the vast majority of our treatments for neurological and psychiatric diseases focus on the chemical part,” explained Dr. Nader Pouratian, a UCLA neurosurgeon working with Markovic. “The goal with devices like the one that Dr. Markovic is creating is to target the electrical abnormalities that occur in the brain as a result of neurological and psychiatric disease.”
Added Markovic, “We are looking into patients that have tried pharmaceuticals. In some people, pharmaceuticals have some effect, but there are a sizeable amount of people where pharmaceuticals do not help.”
On a parallel track, Markovic’s technology also offers scientists a powerful magnifying glass into the inner workings of the brain. One of his collaborators is Nanthia Suthana, a UCLA assistant professor at the Jane and Terry Semel Institute for Neuroscience and Human Behavior who studies neuromodulation and neuroimaging.
“The research potential is really endless with such a device,” Suthana said. “Relevant to my own research field, we will be able to investigate the role of single neuron and local field potential activity in freely moving human behaviors such as in spatial navigation, learning and memory.”
“These newer details will allow us to better understand the neuronal mechanisms that support typical human brain functions as well as abnormalities that may occur in neurologic and psychiatric disorders such epilepsy,” she added.
[Letter to the Editor] Societá Italiana de Fisioterapia and the Physiotherapy Evidence Database (PEDro) – Full Text
This paper provides an overview of a free resource that can be used by physiotherapists to assist their efforts to undertake evidence-based practice. The resource is the Physiotherapy Evidence Database (PEDro; www.pedro.org.au) – a searchable online database that in February 2019 indexes the details of over 42,000 pieces of published evidence about the effects of physiotherapy interventions. PEDro is searched millions of times each year by users worldwide. Societá Italiana de Fisioterapia (SIF; www.sif-fisioterapia.it) has entered into a collaboration with the developers of PEDro. In addition to describing the evidence available on PEDro and who uses it, this paper also summarises the features of PEDro that can facilitate evidence-based physiotherapy. This paper concludes by outlining the collaboration between SIF and PEDro.
The approach to the clinical care of patients known as “evidence-based practice” is becoming more widely accepted within the physiotherapy profession. The approach was defined by its developers as the “integration of the best research evidence with clinical expertise and patient values” . Clinical physiotherapists who want their practice to be evidence-based must therefore identify the best evidence that is available to help inform their decisions about patient management.
It is difficult for physiotherapists to keep abreast of all the research that might be relevant to the types of patients they treat in clinical practice. One contributor to this difficulty is that, with ongoing publications, the number of trials of physiotherapy interventions is growing exponentially [2, 3]. If we consider physiotherapists who graduated in 2011, their university training could only have been based on about half of the evidence that currently exists about the efficacy of physiotherapy interventions. Another issue is that it can be laborious to find the relevant evidence on databases. For example, if a physiotherapist wanted to find evidence about the effects of physiotherapy treatments for knee osteoarthritis, a search of ‘knee osteoarthritis’ on the PubMed database in February 2019 returned over 31,500 articles, many of which have nothing to do with physiotherapy interventions. Searching can be targeted towards more relevant articles but this requires a knowledge of sophisticated search strategies, which involve category searches, Medical Subject Headings (MeSH) terms, Boolean operators, truncation and quotations [4, 5]. This inefficiency is an important issue because most clinical physiotherapists have limited time to find and read evidence. It would be simpler and more efficient if physiotherapists seeking evidence to guide their clinical practice could use a database that indexed only research publications about the effects of physiotherapy interventions.
To address the situation described above, a group of physiotherapists established the Physiotherapy Evidence Database. More commonly referred to as ‘PEDro’, the database is freely available for anyone to use at www.pedro.org.au. This section of the paper will describe the content and features of PEDro, relating these to how they can assist physiotherapists who want to keep abreast of the growing body of evidence about physiotherapy interventions. This section will conclude with a review of how often and how widely PEDro is used
Content of PEDro
Evidence indexed on PEDro
PEDro indexes the bibliographic details and abstracts of three types of documents. One type of document is randomised clinical trials of physiotherapy interventions (or interventions that could become part of physiotherapy care). Another type of document is systematic reviews that include at least one randomised trial of a physiotherapy intervention.1 The third type of document is clinical practice guidelines that are based on a systematic literature search and that contain at least one recommendation relevant to physiotherapy practice. Although there are other forms of evidence (for example, inception cohort studies provide evidence about prognosis), the most unbiased evidence about the effects of interventions comes from the forms of evidence indexed on PEDro: randomised trials, systematic reviews and clinical practice guidelines.
PhysioFunction are recognised as international experts in the use of Functional Electrical Stimulation (FES). We ensure our clients receive the most clinically correct rehabilitation technology suited to their needs. Jon Graham, Clinical Director at PhysioFunction talks about Foot Drop and Functional Electrical Stimulation.
In this video I explain all about bitemporal hemianopia. This is a condition that you might find in patients with pituitary tumours and acromegaly when the tumour grows large enough to press on the optic chiasm. This space occupying lesion causes compression and interrupts the signals innervating the inner portion of the retina, which is responsible for sensing the visual signals from the outer portion of the visual fields. This video is intended to help with the education and understanding of students of healthcare professions only and is not medical advice. For medical advice see your doctor or other healthcare professional. Whilst significant effort has been taken to make the information accurate it cannot be guaranteed.
Functional electrical stimulation is a biophysical technology that have seen increased use in the management of neurological disorders. This talk will discuss principles of use with specific therapeutic cases and would be of primary interest to occupational and physical therapists. The participant will develop skills necessary to choose appropriately and apply electrotherapy in the rehabilitation setting. Various new technologies using electrotherapy will also be demonstrated.
This video aims to give you an idea of what’s required in the Upper Limb Neurological Examination OSCE. Check out the Geeky Medics quiz platform, with over 700 free medical MCQs: https://geekyquiz.com