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AANEM Annual Meeting

Access daily, concise peer-reviewed reports from the AANEM Annual Meeting selected by the Neurology Today editors.

Friday, October 18, 2019

Influenza Vaccine Is Recommended for Autoimmune Neuromuscular Diseases

​AUSTIN, TX—Most neurologists surveyed said they would recommend an influenza vaccine for patients with autoimmune neuromuscular diseases, such as myasthenia gravis (MG) or chronic inflammatory demyelinating polyneuropathy (CIDP), researchers reported here at the annual meeting of the American Association of Neuromuscular & Electrodiagnostic Medicine.

About 82.7 percent of the neurologists who responded to the online questionnaires said they would recommend influenza vaccines to their patients with MG, and 59.1 percent indicated they would recommend the influenza vaccine for patients with a history of CIDP. But less than half—42.7 percent—of the 184 respondents said they would recommend the influenza vaccine for patients with Guillain–Barré syndrome (GBS), Tess Litchman, a fourth-year medical student at Yale University, reported.

In the survey, neurologists said they observed disease exacerbations among 1.5 percent of patients with MG who were vaccinated; 3.7 percent of the CIDP patients, and 8.7 percent of the GBS patients. The higher percentage of GBS patients who had disease activation within six weeks of receiving the influenza vaccination was statistically significant (p< 0.001), Litchman said.

"This survey demonstrates that clearer guidelines and education from a professional academic neurology society is an unmet need and would be helpful to better inform the neurology community about the possible risks and benefits of immunization in MG, CIDP, and GBS patients," Litchman suggested.

She noted that existing guidelines on influenza vaccination from the Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices suggest that all patients with MG and CIDP should be vaccinated, as well as GBS patients who did not develop the disease after receiving an influenza vaccine in the past.

Commenting on the study, Sarah Jones, MD, assistant professor of neurology at the University of Virginia in Charlottesville, told Neurology Today At the Meetings that she basically follows the recommendations outlined by the CDC, and that the results of the survey should be viewed with caution.

"There is pretty good evidence that folks with myasthenia gravis, even when they are on medication, have a pretty robust response that is equal to peers that are not on immunosuppressive medicine and healthy control subjects, and the literature indicates that vaccines are considered safe and do not result in exacerbation of myasthenia gravis."

She added that she would follow CDC guidance that recommends not administering the vaccine to GBS syndrome patients who had developed GBS after receiving influenza vaccination in the past.

"I would recommend vaccinating all other GBS patients and those with MG and CIDP.  I do think the benefit of the vaccine outweighs the potential risk."

Litchman disclosed no relevant relationships with the industry. Dr. Jones disclosed relevant relationships with Argenx and Orphazyme.

Link Up for Related Information:

CDC epidemiology and prevention of vaccine-preventable diseases

Friday, October 18, 2019

MUNIX Test Characterizes Healthy Levels of Motor Neurons

​AUSTIN, TX—Researchers have established reference figures for measuring functional motor neurons in healthy patients, which may help doctors mark the progression of neuromuscular diseases in their patients, according to a poster presentation here at the annual meeting of the American Association of Neuromuscular & Electrodiagnostic Medicine.

In reporting the results, Bei Cao, MD, a fellow in neurology at West China Hospital of Sichuan University, Chengdu, China, said, "The motor unit number index (MUNIX) and the motor unit size index (MUSIX) showed good reproducibility in a large sample of healthy volunteers."

Dr. Cao and colleagues recruited 74 women and 76 men to undergo various tests to determine MUNIX and MUSIX levels in five muscles: the right abductor pollicis brevis, abductor digiti minimi, biceps brachii, tibialis anterior, and trapezius.

"The establishment of the reference values for these five muscles from [people with] a wide age range will aid the application of the MUNIX an MUSIX in more clinical trials and in the clinical diagnosis of neuromuscular disease," she told Neurology Today At the Meetings.

Dr. Cao illustrated in the study that the MUNIX and MUSIX levels for healthy men and women were about the same. She had about 25 people in each age group—starting with volunteers in their 20s and including those up to their 70s. Overall, she said, there were few changes in the MUNIX and MUSIX levels until patients reached later ages. "We all get weaker when we get old," Dr. Cao said.

She suggested that her work would fill a void because, to date, no reference values have been established for MUNIX or MUSIX.

She said the study determined that the reference values for MUNIX were a mean index of 181.2 for the right abductor pollicis brevis; 159.4 for abductor digiti minimi; 166.3 for biceps brachii; 147.4 for tibailis anterior, and 163.8 for trapezius.

Dr. Cao recruited volunteers for the study from December 2017 to February 2019. They were excluded if they had suspected diseases that could influence the measurements such as peripheral nerve lesions, polyneuropathy, radiculopathy, motor neuron disease, or tremor. The volunteers also had no evidence of alcohol use, diabetes, or other risk factors for peripheral neuropathy.

Commenting on the study, Adel Marei, MD, a research fellow in neurology at the Hospital for Special Surgery in New York City, told Neurology Today At the Meetings: "This a good start because we need these baseline values for research and clinical studies. The number of subjects in the study—150—is impressive, and it is interesting that they did values for men and women."

"Because all the volunteers in this study are Chinese, there is a possibility that there is an ethnicity bias in the study," Dr. Marei said. "It should be replicated in other ethnic groups. There also should be a family history because while these individuals did not have diseases such as diabetes, if diabetes is prevalent in the family it could have an impact on the figures in this group as well."

Dr. Cao and Dr. Marei disclosed no relevant relationships with industry.

Link Up for Related Information:

Fatehi F, Grapperon AM, Fathi D, et al. The utility of motor unit number index: A systematic review. Neurophysiol Clin 2018;48(5):251–259.

Friday, October 18, 2019

Data Support Botulinum for Spasticity at 10-Week Intervals

​AUSTIN, TX—Measurement of reflex activity of calf muscles appears to show how long treatment of spasticity with botulinum toxin is effective and could lead to changes in the interval of treatment with the agent, researchers said here at the annual meeting of the American Association of Neuromuscular & Electrodiagnostic Medicine.

In reporting the results of the pilot study, Robin Warner, DO, a clinical fellow in neuromuscular medicine at the Hospital for Special Surgery in New York City, said that clinicians should consider retreating with botulinum toxin after 10 weeks, rather than the 12-week interval generally employed now.

For the study, Dr. Warner tested the H-reflex and M-wave measurement of two patients who met criteria for inclusion in the study. She found that upon injection of the toxin there was a decrease of the measurements to a nadir recorded at two to four weeks after the intramuscular injection. But as time went on, the H-reflex—a marker of spasticity—and M-wave levels rebounded, returning to baseline measurements after 10 weeks. Similarly, she said at her poster presentation, the current required to elicit an H-reflex increased initially and then returned to baseline.

"According to these data, botulinum toxin injections typically wear off at about the 10-week mark," Dr. Warner said. "This supports the practice of administration every 10 weeks instead of the traditional every 12-week interval."

"This is more of a pilot study," Dr. Warner said. "I am hoping that somebody will pick up the idea and go forward with it."

Dr. Warner acknowledged that her study was hampered by "difficulty in recruiting patients in general and specifically patients who were naive to botulinum treatment." She noted that botulinum toxin is a recognized effective treatment for spasticity. 

"Both patients studied had previous treatment and that made it difficult to determine baseline electromyography values. She said larger studies would be needed to replicate her work and to be able to make a strong recommendation to change the treatment schedule.

Dr. Warner said her ultimate goal would be to determine if using these measurements would make it possible to determine if operant conditioning, a proposed biofeedback treatment, is an effective therapy in patients with spasticity.

Commenting on the poster presentation, Rami Hachwi, MD, a neuromuscular medicine specialist with Kaiser Permanente, San Diego, said: "This is a nice study, but it included just two patients. You also have to consider that botulinum toxin treatment may affect the readings. They are doing electromyography on muscles that are paralyzed by the toxin and I am not sure what the yield would be in these cases."

"This is an interesting observation but at this point it doesn't give us anything that we could use clinically," he told Neurology Today At the Meetings.

Bhaskar Roy, MD, assistant professor of neurology at Yale University, added: "We talk about the effect of botulinum toxin on neuromuscular disease, but we really don't have a lot of data regarding what botulinum toxin does. So, this is interesting work. Because of the small numbers of patients, it is not enough to say anything definitively but the researchers are gathering more data so it still could be helpful."

Drs. Warner and Hachwi disclosed no relevant relationships with industry. Dr. Roy disclosed relevant relationships with Alexion Pharmaceuticals.

Link Up for Related Information:

Chan AK, Finlayson H, Mills PB. Does the method of botulinum neurotoxin injection for limb spasticity affect outcomes? A systematic review. Clin Rehabil 2017;31(6):713–721.

Thursday, October 17, 2019

Neuromuscular Complications Follow Radiation for Hodgkin's Lymphoma Decades Later

AUSTIN, TX—Uncommon neuromuscular complications can arise among patients treated with radiation for Hodgkin's lymphoma decades after the treatment has been completed, researchers reported here at the annual meeting of the American Association of Neuromuscular & Electrodiagnostic Medicine.

The complications became apparent in a review of medical charts of 4,100 patients who underwent radiation therapy for lymphoma from 1994 to 2016. Tatsuya Oishi, MD, a fellow in neurology at the Mayo Clinic in Rochester, MN, reported that 4.7 percent of these individuals later presented with neuromuscular complications—with a mean latency of 23.9 years.

"At first glance the history of Hodgkin's lymphoma cured over 20 years ago seems irrelevant to a neurologist, but this may be the only remaining explanation once all other etiology of new-onset weakness is ruled out," study co-author Christopher Klein, MD, professor of neurology at the Mayo Clinic in Rochester, MN, told Neurology Today At the Meetings. "Although treatment is mainly supportive, the clinical awareness and education of both the physicians and patients, as well as prompt access to rehabilitation medicine are nonetheless important."

In his oral presentation, Dr. Oishi reported that 73 patients had myopathy; 54 were diagnosed with plexopathy; 53 had myelopathy; and 25 had polyradiculopathy. He said that other notable findings included benign and malignant nerve sheath tumors in nine patients; mononeuropathies—phrenic and long thoracic—among 14 patients, and compressive spinal meningioma in four individuals.

"The head drop syndrome following radiation therapy is probably the best recognized neuromuscular sequelae and included in the current Hodgkin's lymphoma survivorship guidelines written by hematology experts," Dr. Oishi told Neurology Today At the Meetings. "Beyond this, other delayed complications such as myelopathy or plexopathy are seldom mentioned, but the actual frequency of such presentations were unknown up until now. I hope that by demonstrating the diversity of neuromuscular-axis complications and the non-trivial rate of occurrences, this will improve recognition among health care workers."

He said the interest in the study arose out of an investigation of a particular case of a patient diagnosed with polyradiculopathy. It turned out the condition was secondary to radiation-induced cavernous malformation of the nerve roots, present in the field of radiation from Hodgkin's lymphoma treatment 16 years prior, he said.

"The recognition of the Hodgkin's lymphoma history and radiation therapy, considering the possibility of delayed radiation effects, and regular monitoring of neurologic function is key," Dr. Oishi said.

Dr. Klein added: "On average I see one to four cases per year in our EMG lab or in the subspecialty peripheral nerve clinic. Many of the cases in our manuscript series I have seen in my own practice, including the patient who eluded diagnosis and had himself forgotten to mention to doctors he had radiation as a young man. That patient was discovered when we eventually saw his radiation tattoos."

"Our recommendation is that all the neuromuscular complications we list need to be discussed with patients [when they receive radiation]," Dr. Klein said. "If patients are empowered with this knowledge, they will remember to tell doctors they had radiation long ago. Specifically, even in neurology notes,15 percent of these cases were initially without any documentation of prior Hodgkin's. I think we need to do better in educating both health care providers, and I think if we expand survivorship guidelines patients can educate their providers."

Commenting on the study, Anuj Goenka, MD, co-director of the brain tumor program at Northwell Health Cancer Institute and assistant professor of radiation medicine at the Zucker School of Medicine at Hofstra University in Lake Success, NY said: "The data presented highlight the importance of long-term follow-up for all cancer patients that receive treatment. Historically, Hodgkin's lymphoma was treated with high doses of radiation therapy to very large areas, exposing normal tissue to high doses of radiation."

"While this resulted in acceptable cure rates, long-term toxicities as described in this paper were not infrequent," Dr. Goenka said. "Over the previous two decades, however, major changes have been made to improve upon this. The incorporation of modern chemotherapy and imaging techniques has revolutionized how radiation is delivered.

"When radiation is given, we now prescribe dramatically lower doses of radiation than in the past, and we treat a much more targeted area, thereby reducing normal tissue exposed to radiation. Modern doses of radiation given to small volumes of tissue are felt to be unlikely to cause the majority of symptoms described in this study."

Dr. Klein disclosed relevant relationships with Akcea Therapeutics. Drs. Oishi and Goenka had no disclosures.

Link Up for Related Information:

Stubblefield MD. Neuromuscular complications of radiation therapy. Muscle Nerve 2017;56(6):1031–1040.

Thursday, October 17, 2019

Errors in Judgement Lead to ALS Misdiagnoses, Study Finds

By Ed Susman

AUSTIN, TX—Errors in judgement and diagnostic biases may lead to delays in diagnosis and misdiagnoses of amyotrophic lateral sclerosis (ALS), according to a report presented here at the annual meeting of the American Association of Neuromuscular & Electrodiagnostic Medicine.

The report sought to analyze how different strategies clinicians use to make medical judgements and decisions—referred to as "heuristics"— may lead to missed or inaccurate diagnoses of ALS. They found certain heuristics were more common for veterans with ALS than for non-veterans with the disorder.

"What we did with this study was to determine why there were misdiagnoses and what we can do to correct those errors from occurring," the senior study author Raghav Govindarajan, MD, told Neurology Today At the Meetings.

"One thing we can do in training physicians is to teach them about how these heuristic errors can occur," said Dr. Govindarajan, associate professor of neurology at the University of Missouri. "It is not enough to teach students how to diagnose, but to teach them how it is possible to misdiagnose, and why that happens. It should be at the forefront of the curriculum for students as well as long-time practitioners like me."

For the study, Catherine Rodriguez, a medical student at the University of Missouri, and colleagues reviewed electronic medical records and the treatment course of 88 ALS patients seen at the University of Missouri Hospital in Columbia from 2011 to 2017. They collected demographic information and clinical characteristics of their ALS. If the patient received an incorrect diagnosis, the researchers recorded the number of physicians seen, the type of diagnostic error, clinical factors contributing to the misdiagnosis, and the type of physician who gave the incorrect diagnosis.

The study found that veterans were more often misdiagnosed due to the "availability" heuristic, while non-veterans were misdiagnosed due to the "anchoring" heuristic (p< 0.05).

"When you see a patient such as a veteran and you have experiences with other veterans who tend to have certain characteristics and complaints, you may think that the patient in front of you fits into that same mold—this is known as the availability heuristic," Dr. Govindarajan explained.

The anchoring heuristic refers to the human tendency to accept and rely on the first piece of information received before making a decision, he said. That first piece of information is the anchor and sets the tone for everything that follows.

In the anchoring heuristic, Dr. Govindarajan said, a patient may come to the emergency department with a cough and a cold and because the physician has seen a lot of patients with influenza, he or she determines that this is another case of influenza.

"We expected that anchoring and availability heuristic errors would be equal between veterans and non-veterans, but we didn't see that," Dr. Govindarajan said.

Dr. Govindarajan cited another example. "I had a patient who had complained that he was getting weak and that he was falling, and he had a history in the past of alcohol use. The person who had been treating him [and referred him to me] diagnosed his problem as neuropathy due to alcohol use," Dr. Govindarajan said. "But when things got worse we found out that he had ALS."

"This kind of availability heuristic leads to a delay in diagnosis and treatment," he said, "and in a lot of patients, they may undergo unnecessary treatment, even surgery. It delays the patients from reaching specialized ALS multidisciplinary clinics, which studies have shown can lead to better outcomes—a better quality of life."

"Lower limb onset was most commonly misdiagnosed due to the anchoring heuristic (p< 0.05)," Rodriguez reported in the study abstract. "Bulbar onset was most commonly misdiagnosed due to the availability heuristic (p< 0.05), and surgical intervention was the most common treatment for an incorrect diagnosis (p< 0.05).

"Absence of upper motor neuron signs on examination, presence of sensory symptoms, and absence of tongue fasciculations are common causes of ALS misdiagnosis," Rodriguez reported.

Commenting on the study, Scott M. Friedenberg, MD, director of the ALS Clinic at Geisinger Medical Center in Danville, PA, said ALS can be very challenging to diagnose as it is "incredibly rare, and there are many things that mimic it."

He noted that in the current study, there were 88 patients in seven years, which amounted to approximately one patient a month.

He pointed out that diabetes is common as is trauma among veterans—so a doctor might leap to thinking that these patients have a complication of diabetes or back injury, and may not immediately recognize the neuromuscular nature of the disease.

"With the veterans, you consider that you have seen a lot of diabetics that have nerve problems, and you are looking at a veteran who is diabetic, so you go down that road," he said.

"For the non-veterans, the physician may be grabbing for a specific feature that has been logged in their memory and associated with that individual patient," he said.

"What is happening in both cases is that the physician is not able to take a step back and see the whole picture," Dr. Friedenberg said. "In order to reach a diagnosis of ALS you have to have a broad picture of the patients."

Dr. Friedenberg said that neurologists who eventually have patients with ALS referred to them should go back to the referring physician to discuss the case, in hopes of educating them as to what they saw in the patients and to ask what the referring physician saw. "We hope to perk their interest in these cases so that the next time they see something out of the ordinary, they will think about referring to a specialist. By communicating with the primary care physician or the referring neurologist we can alert them to other cases that may arise in the future."

Dr. Govindarajan disclosed relevant relationships with MT Pharma. Rodriguez and Dr. Friedenberg disclosed no relevant relationships with industry.

Link Up for Related Information:

Palese F, Sartori A, Logroscino G, Pisa FE. Predictors of diagnostic delay in amyotrophic lateral sclerosis: A cohort study based on administrative and electronic medical records data. Amyotroph Lateral Scler Frontotemporal Degener 2019;20(3–4):176–185.