Friday, June 3, 2016

I am a Conscious Craftie

I am so excited to day. I have been chosen to be a part of a wonderful community of crafters-


Conscious Crafties is a handmade craft buying and selling community for creative people living with chronic illness, disability or caring for those affected. It's built by a Spoonie for Spoonies. come visit me at https://www.consciouscrafties.com/Crafties/jewelry-by-la-cash/

Friday, May 13, 2016

Rare Insight: A Physician’s Perspective on Myasthenia Gravis

- As a physician specializing in the treatment of myasthenia gravis (MG), a rare, debilitating neurological disorder, I witness on a daily basis the adversities my patients face. Imagine being a hard-working, active adult—a mom who drove her kids to school every day, who liked to garden and exercise—suddenly faced with a disease that makes it difficult to see, walk or even talk. This is the reality of MG. It steals muscle strength to the point where those living with the disorder can no longer do the things they love. But many fight back, and I am consistently inspired by the strength and perseverance my patients exhibit to overcome these challenges and to not let their disease define them.

June is an important month for the MG community because it marks Myasthenia Gravis Awareness Month—a time when the community can come together, share experiences, and increase awareness for this rare, debilitating disorder. For me, this month provides a key opportunity to leverage my experiences seeing and treating patients with MG to elevate the public’s understanding of the disease and call attention to the special challenges faced by those living with it, including the need for improved diagnostic approaches and new, effective treatment options.Diagnosing and Treating MG

In the United States, a rare disease is one that affects fewer than 200,000 patients.1 While the number of patients affected may be small, the impact of rare diseases on patients, their families, and society is profound.

Like other rare diseases, people living with MG often face a long road to diagnosis since many physicians are unfamiliar with the signs and symptoms of MG. As a result, it may take patients several years before they are accurately diagnosed with MG and can begin treatment.2

Even then, there is no cure for MG, meaning people living with this disease cope with it over the course of their lives. While there are treatment options available that can help manage symptoms in many patients, some patients find that their disease is not adequately controlled with therapies. In fact, as many as 15 percent of MG patients have refractory MG—meaning that despite current treatment, they continue to suffer from debilitating muscle weakness that severely impairs their ability to engage in simple daily activities.3Living with MG

Significant muscle weakness is the hallmark symptom of MG, but no two people experience MG exactly the same way. Basic functions that many take for granted—like chewing, swallowing and walking —become difficult. Other common symptoms include drooping eyelids, blurred vision, slurred speech, and weakness in the arms and legs. Between 15 and 20 percent of MG patients will experience a “myasthenic crisis”—difficulty breathing that can require hospitalization and may be life-threatening.4

While the physicality of this disorder is debilitating, the emotional strain MG patients experience can be just as devastating. Many MG patients feel isolated and worry they are losing their identity. Because of their symptoms, many have had to give up their careers and may feel like a burden to their families both financially and socially. Relationships and friendships can suffer since any day can bring debilitating symptoms that force patients to cancel plans. The ability to travel, or even take a quick trip to the grocery store, may diminish, further compounding feelings of isolation.What’s Next for MG

For MG patients, learning to cope with a lifelong disease can be daunting, so it’s important to focus on cultivating a support system to help overcome challenges. Family, friends, fellow MG patients, and physicians all play a role in helping patients get through difficult times and cheering them on through the great times.

Today, I am optimistic about what the future holds for people living with MG. Unlike some rare diseases, MG is an active area of research, with new clinical trials under way. I am especially hopeful that new research may benefit patients with refractory MG—who continue to suffer without adequate treatment options.

My hope for the MG community is that the scientific advances over the past 30 years—and particularly today’s research—will lead to a better quality of life for patients with this disorder. Please join me today, and every day during the month of June, in celebrating Myasthenia Gravis Awareness Month and spreading the word about this rare disease.

For more information about MG, including education, support, and resources for people living with MG and their families, visit the Myasthenia Gravis Foundation of America website at www.myasthenia.org.

James F. Howard Jr., M.D., is a Distinguished Professor of Neuromuscular Disease and Professor of Neurology & Medicine at the University of North Carolina at Chapel Hill School of Medicine.

Wednesday, April 27, 2016

Study explores two new antibodies believed to cause myasthenia gravis

A study of patients from across the nation with myasthenia gravis is helping determine the incidence of two new antibodies believed to cause the disease, and whether these patients need different treatment strategies.
Researchers are examining the blood of patients from 22 centers specializing in the treatment of mysathenia gravis, the most common communication problem between brain and muscle, to determine what percentage of patients have one or both of the new antibodies and to characterize their clinical symptoms, said Dr. Lin Mei, chairman of the Department of Neuroscience and Regenerative Medicine at the Medical College of Georgia at Augusta University.
About 10 percent of patients have no evidence of two other antibodies already known to cause the disease, although they have classic clinical symptoms such as drooping eyelids, generalized muscle weakness and problems breathing, and electrical studies of their brain-muscle communication indicate a problem.
These so-called double-negative patients are the target for the new study, which is testing their blood for antibodies to two proteins, agrin and LRP4, that Mei's lab has shown are also critical to healthy brain-muscle communication.
Antibodies to agrin and LRP4 have already been found in some patients, and LPR4 antibodies cause myasthenia gravis-like symptoms when injected into lab animals.
"We want to know whether these patients have any unique symptoms so we can diagnose them early then confirm their diagnosis with a blood test," said Mei, Georgia Research Alliance Eminent Scholar in Neuroscience and principal investigator on the new $3 million National Instiutes of Health grant. He notes that several companies already are interested in developing agrin and LRP4 antibody tests.
"These patients may very well have slightly different symptoms because of where these antibodies are acting," said Dr. Michael H. Rivner, MCG neurologist specializing in neuromuscular disease who directs the Electrodiagnostic Medicine Laboratory at Augusta University Medical Center and follows about 250 patients with myasthenia gravis. "Obviously if you get a blood test that shows something, you feel much better about the diagnosis," added Rivner, co-investigator on the new grant.
Two antibodies already considered causative include one for the receptor for acetylcholine, a chemical released by neurons, which activates muscle cell receptors. The other is an antibody to MuSK, an enzyme that supports the clustering of these receptors on the surface of muscle cells.
Mei's lab found a link between agrin and LRP4 in 2008, reported LRP4 antibodies as a new cause of myasthenia gravis in 2013 and that agrin antibodies were associated with the disease the next year. Those findings have already filled in some important knowledge blanks in how the brain and muscle connect during development and continue to interact lifelong.
During development, agrin is released by motor neurons to direct construction of the nerve-muscle contact, or synapse, and MuSK, an enzyme on the muscle cell surface, enables a clustering of receptors, which are activated by acetylcholine. While agrin and MuSK work together, they don't directly communicate, which is where LRP4 comes in. Mei's lab has shown that agrin communicates with LRP4 on the muscle cell surface, then recruits MuSK to join the conversation. LRP4 and MuSK become major components of the receptor needed for the muscle cell to receive the message agrin is sending throughout life.
Mei and his colleagues first identified the antibodies to agrin and LRP4 in the blood of patients who were double-negative. They went back to the laboratory and showed the antibodies to LRP4 cause myasthenia gravis symptoms in animal models. The new grant has them looking at animal models again to learn more about how LRP4 and agrin antibodies cause disease. This includes removing the two antibodies from patients then giving those to lab animals to see if both cause disease. They theorize the antibodies diminish signaling between agrin, LRP4 and MuSK and/or stimulate an immune attack against the neuromuscular junction.
Nearly 900 of the 4,500 patients with myasthenia gravis being followed at centers across the nation, such as Augusta University Medical Center, are double-negative. Over the next five years, more than 600 of those patients will have their blood tested for the two new antibodies. Similar studies will be done on the blood of healthy individuals as well as patients with other neurological problems such as Alzheimer's and stroke, both to ensure that the antibodies' presence is not random and to begin to collect evidence about whether they also contribute to other maladies, Mei said.
Thorough physical exams will look for any clinical distinctions in patients who test positive for the new antibodies. Research also will document their response to treatment.
Study participants will have other specialized testing, including single fiber electromyography, which looks at the electrical response of a single muscle fiber instead of the group of fibers controlled by a single motor neuron. Patients typically get this type of detailed analysis to help establish a diagnosis.
"Every time there is an action potential in this motor neuron, you should see a response occur within a certain amount of time. But if you have a defective neuromuscular junction, it may take longer for it to fire, or it won't happen at all," Rivner said, noting there tends to be plenty of neurotransmitter but too few receptors for a proper response.
When the MCG researchers immunize mice, rabbits and other animals to induce LRP4 antibodies, the animals show classic signs of myasthenia gravis and tend to be less active, although they can survive for long periods, Mei said. When they examine the neuromuscular junction, they can see its disentegration. An EMG shows the poor communication, which Mei likens to a personal relationship with no communication. "Things don't go well," he said.
Since word has spread of the previous studies identifying the new antibodies, the medical school has gotten numerous requests for testing of double-negative patients. Other centers have started doing limited testing, and early reports of the incidence of the newest antibodies vary dramatically in patients who are double-negative, another reason to consistenly look at incidence in a large number of patients, Mei said.
Whatever the cause, disease symptoms tend to respond well to therapy, which typically includes chronic use of drugs that suppress the immune response, Rivner said. However, immunosuppressive drugs carry significant risk, including infection, cancer and weight gain. "We would definitely like to have better treatments than we have now," Rivner said.
Removal of the thymus, a sort of classroom where directors of the immune response, called T cells, learn early what to attack and what to ignore, is another common therapy for myasthenia gravis. While the gland usually atrophies in adults, patients with myasthenia gravis tend to have enlarged glands. Rivner is part of another NIH-funded study to determine whether gland removal really benefits patients. Other therapies include a plasma exchange for acutely ill patients.
Source:
Medical College of Georgia at Augusta University

Thursday, February 11, 2016

Instructions for anaesthetists

Instructions for anaesthetists



In patients with myasthenia gravis should respect certain principles applicable to the anesthesia.
The recommended method for perioperative care for patients with myasthenia gravis. 1. Critical conditions associated with myasthenia gravis (MG):
1.1 Development of cholinergic crisis:
Cholinergic crisis caused by absolute or relative overdose inhibitors cholinesterase (ICHE) used in the treatment of MG: pyridostigmin (Mestinon), distigmin (Ubretid), neostigmine (Syntostigmin). It is characterized by a combination of nicotine symptoms (tremor, fasciculations, twitching, muscle weakness) and autonomous muscarinic symptoms (hypersalivation, bronchial hypersecretion, nausea, vomiting, diarrhea, abdominal pain, bradycardia, miosis). When administered anticholinergics may the autonomous signs mitigované. In that case, you can use in the differential diagnosis effect neostigmine: if after worsening muscle weakness, it is probably cholinergic crisis.
1.2 The development of myasthenic crisis, the need for protracted mechanical ventilation The development of myasthenic crisis may be a natural course of disease psychological or physical stress, infections with hyperpyrexia, or improper administration medication. Among the drugs affecting neuromuscular transmission is used in many preparations in anaesthesiology, intensive care and other related fields. Some can be totally avoided (benzodiazepines) for other general point that the indications must be clearly supported and their use is governed by special arrangements (eg, peripheral nondepolarizing muscle relaxants at a reduced dose of a neuromuscular transmission monitoring, etc.).
The main groups of substances affecting neuromuscular transmission:
1.2.1 Benzodiazepines: if possible, do not serve
1.2.2 Central relaxants (guaiphenesine, baclofen ...) do not serve
1.2.3 Peripheral nondepolarizing muscle relaxants: increased sensitivity and prolonged action is appropriate in patients in remission, the ongoing subclinical MG a
d with minimum (eye) symptoms. Generally, we choose the preparation of short-lived and fast. Elimination: atracurium, vecuronium, mivacurium. CAVE:patients treated with the ICHE
be affected by degradation mivacuria cholinesterase. Condition of use:
a. Performance nature necessarily requiring muscle relaxation (laparoscopy,
extensive abdominal interventions ...)
b. Reduction of the initial calculated dose to 20-50%
c. Monitoring of neurumucular transmission (NMT). The monitoring neuromuscular method is mostly used electrical neurostimulation pulse monofazic
using skin electrodes stuck over the course of the selected nerve (mostly n. ulnaris). Motor response (in this case an inch of movement) is scanned accelerometry. Evaluated either an irritation, or four successive stimuli (train of four - TOF). On a similar principle works most of the equipment available, either have separate or integrated in monitoring systems anesthesologic devices. Through the use of reduced dose should always be counted prolonged effect, repeated administration with the exception of extremely long output is not appropriate.
1.2.4 Peripheral nonpolarizing relaxants - succinylcholine (SCHJ) is better
tolerated, its effect may be even smaller than in healthy subjects. Nevertheless, the majority recommends reducing the dose. Repeated administration threatened protracted II. phase blockade.
CAVE: patients treated Iche may be affected by degradation SCHJ cholinesterase.
Before submitting SCHJ not to use the "priming" - even a small dose of relaxant might lead to premature palsy, hypoventilation, DC, and occlusion as a result of prolonged action. Indications for use: the impossibility of endotracheal intubation (ETI), even a mere or inhalation anesthesia particularly with the rapid introduction of a full stomach. NMT monitoring is appropriate.
1.2.5 Volatile inhalation anesthetics: they have a direct effect on neuromuscular transmission, increased potency peripheral relaxants, medication in general is chosen primarily to a shorter elimination (desfluran, sevoflurane).
1.2.6 Local anesthetics (LA) LA increased serum levels may affect the neuromuscular transmission, but the general profit local / regional anesthesia that exceeds the risk. Techniques made with fewer ingredients are sometimes preferred (SAB versus epidural block), the introduction of epidural anesthesia catheter, however, allows better titrovatelnost extent of blockade and postoperative analgesia with a reduction of system-made opioids. Better tolerated the amide LA, patients treated with Iche may be affected by degradation ester-like LA. Procaine is absolutely contraindicated.
1.2.7 Dantrolene: indication is malignant hyperthermia, neuroleptic malignant syndrome, hyperpyrexia of intoxication budivými amines
1.2.8 Corticosteroids: initiation of treatment of indications MG (or other) may cause paradoxical transient worsening of weakness. Conversely, when administered chronically in MG as immunosuppression, is extremely dangerous to their withdrawal.
1.2.9 Antibiotics aminoglycoside, macrolide less, glykopeptidová, doxycycline,
erythromycin, ofloxacin, ciprofoxacin, penicillins, sulfonamides.
1.2.10 Calcium channel blockers
1.2.11 Beta blockers
1.2.12 Magnesium especially in higher doses than 1000 mg po, or even brought
1.2.13 Antiepileptics
1.2.14. Anticholinergics
The group 1.2.10 - 1.2. 14 should always consider the individual benefit versus risk
brought drugs. In the case of increased risk should seek other treatment alternatives.
1.3 The central depression of breath
Risk are all centrally deadening agents: benzodiazepines, sedatives, inhalation and iv. anesthetics, opioids. In general, we choose the preparation of low accumulation and short context --
sensitive half-life, especially when repeated or continuous application.
Patients treated Iche could theoretically be affected by the degradation of remifentanil, however, is recommended.
2. Practical procedure
2.1 Preoperative preparation
2.1.1 The scheduled performance must be achieved by optimizing the state at the cost of less common methods (Application intravenous immunoglobulin, plasmapheresis).
2.1.2 In addition to neurological examination should be considered spirometry. Forced Vital capacity and negative inspiratory pressure are the main markers of ventilatory reserve and respiratory function muscles.
2.1.3 The post-operative care must be in advance of their area ventilated bed.
2.1.4 Chronic therapy (Iche, corticosteroids) is given in the morning the day of surgery and continues the performance of enteral or parenteral form.
2.1.5 Due to the increased fatigue should be normal training as intrusive. It is appropriate to include a patient at the beginning of the operational program, as the morning is physical strength is greatest.
2.1.6 For patients treated with corticosteroids should be increased intraoperative dose (hydrocortizon 50-300 mg hr iv/24 by output range). At the same time is
necessary to prevent ofulcer (omeprazole 40-80 mg/24 h).
2.1.7 In patients receiving immunosuppressive consider ATB prophylaxis with regard to the type operations and risks above certain ATB (see 1.2.11).
2.1.8 Checking and correction mineralogramu ev. electrolyte imbalance is necessary (CAVE hypokalaemia, hypocalcaemia, hypermagnezemie).
2.1.9 Premedication: generally use reduced doses due to the risk of central depression. Benzodiazepines are inappropriate, except tofisopam.At night you can use common nonbenzodiazepins hypnotic (zolpidem - Hypnogen) dithiaden, neuroleptic (tiapride) or morning prometazin im premedication, pethidine im, ev. tiapride. Maybe it i.v. sedation titrated dose of opioids and propofol after navezení the operational wing, when it is sick under constant supervision.
2.2 Selection and management of anesthesia
2.2.1 It is best to use the local/regional techniques, ev. supplemented i.v. sedation
(opioid + propofol). Advantages and disadvantages subarachnoidealversus epidural anesthesia and LA different groups mentioned above (1.2.6).
2.2.2. if the nature of performance or other contraindications (allergy to LA, disagreement patient, Hemorrhagic diathesis ....) impossible to use a regional technique, applicable as a second choice of general anesthesia without any nondepolarizing muscle relaxants: a combination of iv + inhalation, where fund assets, especially for short performances. Appropriate medication: propofol, etomidate, remifentanil, alfentanil, sufentanil, O2/N2O, desfluran, sevoflurane (izofluran) Ensuring DC: facial mask / Airway, ev. laryngeal mask is the first choice. If necessary ETI, then if possible, without SCHJ (introduction propofol, opioids, ev. Inhalation - sevoflurane). SCHJ is essential for the rapid introduction and for the impossibility laryngoscopy / intubation and the
deep anesthesia.
Ventilation: deepening, ev. controlled.
Intolerance endotracheal tube or interference with the fan is not a reason to muscle
relax!
2.2.3 If the nature of the power necessary muscle relaxation, reduced benefits apply
nondepolarizing muscle relaxants for the safeguards provided for in section1.2.3. Tothe extent permitted intubation ratios, it is appropriate to intubate without the concurrent use SCHJ. Be envisaged synergy effect of volatile anesthetics can stop the supply of anesthetic elusive ahead and go the end of the performance i.v. propofol sedation until return dostatečná muscle strength. Use lump dekurarization not appropriate given the risk of cholinergic crisis.
2.3 Postoperative care
2.3.1 Even after extubation, patients must be monitored at least observován bed with fan in reserve. Muscle weakness and hypoventilation with airway obstruction
may manifest after several hours, allowing constant monitoring and adequate analgesia without the risk of central apnea.
2.3.2. Analgesia: The best is regional (epidural) administration. The systemic analgesia is be used titrated i.v. steerable continuous administration of opioids (sufentanil, remifentanil) with advantage in combination with paracetamol  or other analgesic  (metamizol, ketoprofen)
2.3.3 In the treatment of gastrointestinal paresis consulted before ev. administration of neostigmine or distigmin attending physician (neurologist) due to the risk of cholinergic crisis. Prokinetics type metoclopramide are tolerated.

List of abbreviations:
ATB - antibiotics
GIT - gastrointestinal tract
ICHE - cholinesterase inhibitors
LA - Local anesthetics
MG - myasthenia gravis
NMT - neurumuskulární transmission
SAB-subarachnoid block (anesthesia)
SCHJ - succinylcholine
Josef Zavada MD Jiří Piťha MD
General Teaching Hospital Prague, Czech Republic