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Motor neuron disease spasticity improved with cannabis-based oral spray, antispasticity drugs
Nabiximols, a cannabis-based oral spray containing delta-9 tetrahydrocannabinol and cannabidiol, significantly improved spasticity symptoms in combination with antispasticity drugs in patients with motor neuron disease in a randomized, double-blind, placebo-controlled, parallel-group, phase 2 clinical trial.
Nabiximols proved superior to a placebo spray when both were given to patients with either amyotrophic lateral sclerosis or primary lateral sclerosis as part of an antispasticity regimen in the 6-week, CANALS (Cannabis Sativa Extract in Amyotrophic Lateral Sclerosis and other Motor Neuron Disease) study at four Italian centers, Nilo Riva, MD, PhD, of the San Raffaele Scientific Institute in Milan and his colleagues reported in The Lancet Neurology. Nabiximols is approved for the treatment of spasticity due to multiple sclerosis in multiple countries, but not in the United States.
“There is no cure for motor neuron disease, so improved symptom control and quality of life are important for patients,” Dr. Riva stated in a press release. “Our proof-of-concept trial showed a beneficial effect of THC-CBD [delta-9 tetrahydrocannabinol and cannabidiol] spray in people on treatment-resistant spasticity and pain.
“Despite these encouraging findings, we must first confirm that THC-CBD spray is effective and safe in larger, longer-term phase 3 trials,” Dr. Riva added.
The patients enrolled in the phase 2 trial between January 2013 and December 2014 and were between 18 and 80 years old with a probable diagnosis of amyotrophic lateral sclerosis or primary lateral sclerosis, were on an antispasticity regimen for at least 30 days, and had a spasticity score of at least 1 in two muscle groups on the 5-point Modified Ashworth Scale. Participants titrated for the first 2 weeks before maintaining their treatment for 4 weeks.
Of 59 participants at final follow-up, Modified Ashworth Scale scores improved in the nabiximols group (29 participants) by a mean of –0.11 points, compared with worsening by a mean of 0.16 points in the placebo group (30 participants). The researchers noted that there were no participants who withdrew from the study, nabiximols was well-tolerated, and there were no serious adverse events in the nabiximols group; however, there were 22 participants in the nabiximols group and 8 participants in the placebo group who experienced an adverse event from any cause.
“This study is, to our knowledge, the first randomized controlled trial of safety and efficacy of a pharmacological treatment for spasticity and the first trial of nabiximols in motor neuron disease,” Dr. Riva and his colleagues wrote. “Our results suggest that the study drug is well tolerated and provides first evidence of efficacy in terms of controlling spasticity in patients with motor neuron disease.”
The study was funded by the Italian Research Foundation for Amyotrophic Lateral Sclerosis. GW Pharma, which developed nabiximols, provided the study drug and placebo. Many of the authors reported financial disclosures with pharmaceutical companies.
SOURCE: Riva N et al. Lancet Neurol. 2018 Dec 13. doi: 10.1016/S1474-4422(18)30406-X.
Although the results of Riva et al. are encouraging, the study had several major limitations and future research in the form of larger, multicenter, randomized controlled trials is needed, Marianne de Visser, MD, PhD, wrote in a related editorial.
Dr. de Visser noted a bias in the study as it randomized 16 patients with predominantly upper motor neuron involvement to the nabiximols group. The treatment could potentially have benefited those patients, for whom spasticity is the prevailing symptom, more than the 13 patients randomized to the nabiximols group who had classic amyotrophic lateral sclerosis involving both upper and lower neurons. In addition, Riva et al. did not differentiate between patients with upper and lower limb spasticity or patients with bulbar spasticity and those without, she said.
The use of the Modified Ashworth Scale was also a potential issue, because while it has been used in previous studies examining antispastic treatment efficacy, “it lacked sensitivity in studies of the efficacy of cannabinoids in patients with multiple sclerosis–related spasticity, and new spasticity numeric rating or visual analogue scales are being adopted,” Dr. de Visser wrote.
The number of adverse effects in the treatment group could have also unblinded researchers, which may have affected the significant findings, she said.
“Before asking for approval of cannabinoids for symptomatic treatment of spasticity in patients with amyotrophic lateral sclerosis, further studies are needed to establish the frequency of spasticity in the various presentations of motor neuron disease, and also whether reductions in spasticity improve quality of life,” Dr. de Visser said in a press release. “Natural history studies including all subtypes of motor neuron disease and better outcome measures aimed at assessment of spasticity are required. Dr. Riva and colleagues’ data are encouraging, and larger multicenter, randomized controlled trials should be done to identify which subgroups of patients derive clinically significant benefits from nabiximols.”
Marianne de Visser, MD, PhD, is with the department of neurology at Amsterdam University Medical Center. She reported no relevant conflicts of interest. Her remarks are taken from an editorial accompanying the study by Dr. Riva and associates (Lancet Neurol. 2018 Dec 13. doi: 10.1016/S1474-4422[18]30493-9 ).
Although the results of Riva et al. are encouraging, the study had several major limitations and future research in the form of larger, multicenter, randomized controlled trials is needed, Marianne de Visser, MD, PhD, wrote in a related editorial.
Dr. de Visser noted a bias in the study as it randomized 16 patients with predominantly upper motor neuron involvement to the nabiximols group. The treatment could potentially have benefited those patients, for whom spasticity is the prevailing symptom, more than the 13 patients randomized to the nabiximols group who had classic amyotrophic lateral sclerosis involving both upper and lower neurons. In addition, Riva et al. did not differentiate between patients with upper and lower limb spasticity or patients with bulbar spasticity and those without, she said.
The use of the Modified Ashworth Scale was also a potential issue, because while it has been used in previous studies examining antispastic treatment efficacy, “it lacked sensitivity in studies of the efficacy of cannabinoids in patients with multiple sclerosis–related spasticity, and new spasticity numeric rating or visual analogue scales are being adopted,” Dr. de Visser wrote.
The number of adverse effects in the treatment group could have also unblinded researchers, which may have affected the significant findings, she said.
“Before asking for approval of cannabinoids for symptomatic treatment of spasticity in patients with amyotrophic lateral sclerosis, further studies are needed to establish the frequency of spasticity in the various presentations of motor neuron disease, and also whether reductions in spasticity improve quality of life,” Dr. de Visser said in a press release. “Natural history studies including all subtypes of motor neuron disease and better outcome measures aimed at assessment of spasticity are required. Dr. Riva and colleagues’ data are encouraging, and larger multicenter, randomized controlled trials should be done to identify which subgroups of patients derive clinically significant benefits from nabiximols.”
Marianne de Visser, MD, PhD, is with the department of neurology at Amsterdam University Medical Center. She reported no relevant conflicts of interest. Her remarks are taken from an editorial accompanying the study by Dr. Riva and associates (Lancet Neurol. 2018 Dec 13. doi: 10.1016/S1474-4422[18]30493-9 ).
Although the results of Riva et al. are encouraging, the study had several major limitations and future research in the form of larger, multicenter, randomized controlled trials is needed, Marianne de Visser, MD, PhD, wrote in a related editorial.
Dr. de Visser noted a bias in the study as it randomized 16 patients with predominantly upper motor neuron involvement to the nabiximols group. The treatment could potentially have benefited those patients, for whom spasticity is the prevailing symptom, more than the 13 patients randomized to the nabiximols group who had classic amyotrophic lateral sclerosis involving both upper and lower neurons. In addition, Riva et al. did not differentiate between patients with upper and lower limb spasticity or patients with bulbar spasticity and those without, she said.
The use of the Modified Ashworth Scale was also a potential issue, because while it has been used in previous studies examining antispastic treatment efficacy, “it lacked sensitivity in studies of the efficacy of cannabinoids in patients with multiple sclerosis–related spasticity, and new spasticity numeric rating or visual analogue scales are being adopted,” Dr. de Visser wrote.
The number of adverse effects in the treatment group could have also unblinded researchers, which may have affected the significant findings, she said.
“Before asking for approval of cannabinoids for symptomatic treatment of spasticity in patients with amyotrophic lateral sclerosis, further studies are needed to establish the frequency of spasticity in the various presentations of motor neuron disease, and also whether reductions in spasticity improve quality of life,” Dr. de Visser said in a press release. “Natural history studies including all subtypes of motor neuron disease and better outcome measures aimed at assessment of spasticity are required. Dr. Riva and colleagues’ data are encouraging, and larger multicenter, randomized controlled trials should be done to identify which subgroups of patients derive clinically significant benefits from nabiximols.”
Marianne de Visser, MD, PhD, is with the department of neurology at Amsterdam University Medical Center. She reported no relevant conflicts of interest. Her remarks are taken from an editorial accompanying the study by Dr. Riva and associates (Lancet Neurol. 2018 Dec 13. doi: 10.1016/S1474-4422[18]30493-9 ).
Nabiximols, a cannabis-based oral spray containing delta-9 tetrahydrocannabinol and cannabidiol, significantly improved spasticity symptoms in combination with antispasticity drugs in patients with motor neuron disease in a randomized, double-blind, placebo-controlled, parallel-group, phase 2 clinical trial.
Nabiximols proved superior to a placebo spray when both were given to patients with either amyotrophic lateral sclerosis or primary lateral sclerosis as part of an antispasticity regimen in the 6-week, CANALS (Cannabis Sativa Extract in Amyotrophic Lateral Sclerosis and other Motor Neuron Disease) study at four Italian centers, Nilo Riva, MD, PhD, of the San Raffaele Scientific Institute in Milan and his colleagues reported in The Lancet Neurology. Nabiximols is approved for the treatment of spasticity due to multiple sclerosis in multiple countries, but not in the United States.
“There is no cure for motor neuron disease, so improved symptom control and quality of life are important for patients,” Dr. Riva stated in a press release. “Our proof-of-concept trial showed a beneficial effect of THC-CBD [delta-9 tetrahydrocannabinol and cannabidiol] spray in people on treatment-resistant spasticity and pain.
“Despite these encouraging findings, we must first confirm that THC-CBD spray is effective and safe in larger, longer-term phase 3 trials,” Dr. Riva added.
The patients enrolled in the phase 2 trial between January 2013 and December 2014 and were between 18 and 80 years old with a probable diagnosis of amyotrophic lateral sclerosis or primary lateral sclerosis, were on an antispasticity regimen for at least 30 days, and had a spasticity score of at least 1 in two muscle groups on the 5-point Modified Ashworth Scale. Participants titrated for the first 2 weeks before maintaining their treatment for 4 weeks.
Of 59 participants at final follow-up, Modified Ashworth Scale scores improved in the nabiximols group (29 participants) by a mean of –0.11 points, compared with worsening by a mean of 0.16 points in the placebo group (30 participants). The researchers noted that there were no participants who withdrew from the study, nabiximols was well-tolerated, and there were no serious adverse events in the nabiximols group; however, there were 22 participants in the nabiximols group and 8 participants in the placebo group who experienced an adverse event from any cause.
“This study is, to our knowledge, the first randomized controlled trial of safety and efficacy of a pharmacological treatment for spasticity and the first trial of nabiximols in motor neuron disease,” Dr. Riva and his colleagues wrote. “Our results suggest that the study drug is well tolerated and provides first evidence of efficacy in terms of controlling spasticity in patients with motor neuron disease.”
The study was funded by the Italian Research Foundation for Amyotrophic Lateral Sclerosis. GW Pharma, which developed nabiximols, provided the study drug and placebo. Many of the authors reported financial disclosures with pharmaceutical companies.
SOURCE: Riva N et al. Lancet Neurol. 2018 Dec 13. doi: 10.1016/S1474-4422(18)30406-X.
Nabiximols, a cannabis-based oral spray containing delta-9 tetrahydrocannabinol and cannabidiol, significantly improved spasticity symptoms in combination with antispasticity drugs in patients with motor neuron disease in a randomized, double-blind, placebo-controlled, parallel-group, phase 2 clinical trial.
Nabiximols proved superior to a placebo spray when both were given to patients with either amyotrophic lateral sclerosis or primary lateral sclerosis as part of an antispasticity regimen in the 6-week, CANALS (Cannabis Sativa Extract in Amyotrophic Lateral Sclerosis and other Motor Neuron Disease) study at four Italian centers, Nilo Riva, MD, PhD, of the San Raffaele Scientific Institute in Milan and his colleagues reported in The Lancet Neurology. Nabiximols is approved for the treatment of spasticity due to multiple sclerosis in multiple countries, but not in the United States.
“There is no cure for motor neuron disease, so improved symptom control and quality of life are important for patients,” Dr. Riva stated in a press release. “Our proof-of-concept trial showed a beneficial effect of THC-CBD [delta-9 tetrahydrocannabinol and cannabidiol] spray in people on treatment-resistant spasticity and pain.
“Despite these encouraging findings, we must first confirm that THC-CBD spray is effective and safe in larger, longer-term phase 3 trials,” Dr. Riva added.
The patients enrolled in the phase 2 trial between January 2013 and December 2014 and were between 18 and 80 years old with a probable diagnosis of amyotrophic lateral sclerosis or primary lateral sclerosis, were on an antispasticity regimen for at least 30 days, and had a spasticity score of at least 1 in two muscle groups on the 5-point Modified Ashworth Scale. Participants titrated for the first 2 weeks before maintaining their treatment for 4 weeks.
Of 59 participants at final follow-up, Modified Ashworth Scale scores improved in the nabiximols group (29 participants) by a mean of –0.11 points, compared with worsening by a mean of 0.16 points in the placebo group (30 participants). The researchers noted that there were no participants who withdrew from the study, nabiximols was well-tolerated, and there were no serious adverse events in the nabiximols group; however, there were 22 participants in the nabiximols group and 8 participants in the placebo group who experienced an adverse event from any cause.
“This study is, to our knowledge, the first randomized controlled trial of safety and efficacy of a pharmacological treatment for spasticity and the first trial of nabiximols in motor neuron disease,” Dr. Riva and his colleagues wrote. “Our results suggest that the study drug is well tolerated and provides first evidence of efficacy in terms of controlling spasticity in patients with motor neuron disease.”
The study was funded by the Italian Research Foundation for Amyotrophic Lateral Sclerosis. GW Pharma, which developed nabiximols, provided the study drug and placebo. Many of the authors reported financial disclosures with pharmaceutical companies.
SOURCE: Riva N et al. Lancet Neurol. 2018 Dec 13. doi: 10.1016/S1474-4422(18)30406-X.
FROM THE LANCET NEUROLOGY
Key clinical point:
Major finding: In the nabiximols group, Modified Ashworth Scale scores improved by mean of –0.11 points, compared with worsening by a mean of 0.16 points in the placebo group.
Study details: A multicenter, double-blinded, randomized, placebo-controlled, phase 2 trial of 59 participants with spasticity symptoms from motor neuron disease from four tertiary motor neuron centers in Italy.
Disclosures: The study was funded by the Italian Research Foundation for Amyotrophic Lateral Sclerosis. GW Pharma, which developed nabiximols, provided the study drug and placebo. Many of the authors reported financial disclosures with pharmaceutical companies.
Source: Riva N et al. Lancet Neurol. 2018 Dec 13. doi: 10.1016/S1474-4422(18)30406-X
CDC: Acute flaccid myelitis on the decline for 2018
, according to the Centers for Disease Control and Prevention.
Through Nov. 30, 134 cases of AFM in 33 states have been confirmed out of the 299 reported to the CDC. That represents “an increase of 18 confirmed cases from the previous week, but most of the latest confirmed AFM cases occurred in September and October,” the CDC reported Dec. 3.
There has been a pattern of increased AFM cases every other year for the previous 4 years: 120 cases in 2014, 22 cases in 2015, 149 cases in 2016, and 33 cases in 2017. “Most cases are reported between August and October, and a marked reduction in cases is seen in November. That pattern appears to be repeating in 2018 because states have reported fewer [persons under investigation] over the past couple of weeks. CDC expects this decline to continue,” the statement said.
The 16 confirmed cases in Texas are the most for any state this year, followed by Colorado with 15; Ohio with 10; and Illinois, New Jersey, and Washington with 9 each. California and Florida have not had any confirmed cases as of Nov. 30. Since 2014, over 90% of all confirmed AFM cases have occurred in children, the CDC noted.
More information on AFM is available at a CDC website for health care professionals.
, according to the Centers for Disease Control and Prevention.
Through Nov. 30, 134 cases of AFM in 33 states have been confirmed out of the 299 reported to the CDC. That represents “an increase of 18 confirmed cases from the previous week, but most of the latest confirmed AFM cases occurred in September and October,” the CDC reported Dec. 3.
There has been a pattern of increased AFM cases every other year for the previous 4 years: 120 cases in 2014, 22 cases in 2015, 149 cases in 2016, and 33 cases in 2017. “Most cases are reported between August and October, and a marked reduction in cases is seen in November. That pattern appears to be repeating in 2018 because states have reported fewer [persons under investigation] over the past couple of weeks. CDC expects this decline to continue,” the statement said.
The 16 confirmed cases in Texas are the most for any state this year, followed by Colorado with 15; Ohio with 10; and Illinois, New Jersey, and Washington with 9 each. California and Florida have not had any confirmed cases as of Nov. 30. Since 2014, over 90% of all confirmed AFM cases have occurred in children, the CDC noted.
More information on AFM is available at a CDC website for health care professionals.
, according to the Centers for Disease Control and Prevention.
Through Nov. 30, 134 cases of AFM in 33 states have been confirmed out of the 299 reported to the CDC. That represents “an increase of 18 confirmed cases from the previous week, but most of the latest confirmed AFM cases occurred in September and October,” the CDC reported Dec. 3.
There has been a pattern of increased AFM cases every other year for the previous 4 years: 120 cases in 2014, 22 cases in 2015, 149 cases in 2016, and 33 cases in 2017. “Most cases are reported between August and October, and a marked reduction in cases is seen in November. That pattern appears to be repeating in 2018 because states have reported fewer [persons under investigation] over the past couple of weeks. CDC expects this decline to continue,” the statement said.
The 16 confirmed cases in Texas are the most for any state this year, followed by Colorado with 15; Ohio with 10; and Illinois, New Jersey, and Washington with 9 each. California and Florida have not had any confirmed cases as of Nov. 30. Since 2014, over 90% of all confirmed AFM cases have occurred in children, the CDC noted.
More information on AFM is available at a CDC website for health care professionals.
Firdapse approved: First treatment for rare autoimmune disorder
The Food and Drug Administration has approved amifampridine (Firdapse) as the first treatment for the rare autoimmune disorder known as Lambert-Eaton myasthenic syndrome, which causes the immune system to attack the neuromuscular junction and thereby disrupts the nerves’ ability to send signals to muscle cells. This causes fatigue and weakness in those affected, so they can experience difficulties with activities of daily living as a result.
The most common side effects included prickling sensation, upper respiratory tract infection, abdominal pain, and muscle spasms.
More information can be found in the FDA’s press announcement.
cpalmer@mdedge.com
The Food and Drug Administration has approved amifampridine (Firdapse) as the first treatment for the rare autoimmune disorder known as Lambert-Eaton myasthenic syndrome, which causes the immune system to attack the neuromuscular junction and thereby disrupts the nerves’ ability to send signals to muscle cells. This causes fatigue and weakness in those affected, so they can experience difficulties with activities of daily living as a result.
The most common side effects included prickling sensation, upper respiratory tract infection, abdominal pain, and muscle spasms.
More information can be found in the FDA’s press announcement.
cpalmer@mdedge.com
The Food and Drug Administration has approved amifampridine (Firdapse) as the first treatment for the rare autoimmune disorder known as Lambert-Eaton myasthenic syndrome, which causes the immune system to attack the neuromuscular junction and thereby disrupts the nerves’ ability to send signals to muscle cells. This causes fatigue and weakness in those affected, so they can experience difficulties with activities of daily living as a result.
The most common side effects included prickling sensation, upper respiratory tract infection, abdominal pain, and muscle spasms.
More information can be found in the FDA’s press announcement.
cpalmer@mdedge.com
CDC: No medical therapy can yet be recommended for acute flaccid myelitis
The updated guidance on managing acute flaccid myelitis is unlikely to relieve the frustrations of physicians struggling to treat the condition.
After reviewing the extant data on the baffling disorder, the Centers for Disease Control and Prevention found no evidence that corticosteroids, interferon, antivirals, or any other immunologic or biologic therapy is an effective treatment.
All of the treatments mentioned in the guidance have been used anecdotally, and often for cases proven to be associated with enterovirus-related cases. However, there are no well validated studies confirming benefit for any of these approaches, the agency said in its clinical management document.
Acute flaccid myelitis (AFM) has stricken 90 patients in the United States this year and another 252 cases are being investigated, according to new data from the CDC. The number of confirmed cases is triple that seen in 2017. Whether the disease is an infectious or autoimmune process, or something else entirely, remains unknown.
In response to the outbreak – the largest since 2014 – an expert panel of 4 CDC staff physicians reviewed the literature to find what, if any, treatments were effective; another 14 external experts provided input on the recommendations. At this point, nothing can be officially recommended, the agency said.
Corticosteroids
Corticosteroids should not be administered to most patients with AFM. In addition to “a theoretical concern” about the potential adverse effects of these drugs in acute infections, there is some hard evidence that they are associated with worse outcomes in enteroviral neuroinvasive diseases, particularly those caused by EV-71.
This observation, following a 2012 outbreak in Cambodia, led a World Health Organization commission to conclude that corticosteroids were contraindicated in the management of EV-71–associated neuroinvasive disease. This year, there has been an uptick in EV-A71-associated neurologic disease.
The CDC did hedge its advice on corticosteroids a bit in the setting of AFM, however. “There may be theoretical benefit for steroids in the setting of severe cord swelling or long tract signs suggesting white matter involvement, where steroids may salvage tissue that may be harmed due to an ongoing immune/inflammatory response. While AFM is clinically and radiographically defined by the predominance of gray matter damage in the spinal cord, some patients may have some white matter involvement. It is not clear if these different patterns are important relative to therapeutic considerations.”
Nevertheless, the agency does not recommend corticosteroid use for these patients. “The possible benefits of the use of corticosteroids to manage spinal cord edema or white matter involvement in AFM should be balanced with the possible harm due to immunosuppression in the setting of possible viral infection.”
IVIG
While IVIG holds some theoretical benefit for AFM, there are no high-level human data, the guidelines state. The treatment is generally safe and well tolerated, but the few reports of its use in AFM did not show clear benefit. These include two case series. One suggested an acute improvement of neurologic status, but no long-term resolution of deficits. The other indicated neither significant improvement nor deterioration.
However, current practice at Children’s Hospital of Philadelphia is to initiate IVIG therapy at AFM diagnosis in hopes of boosting humoral immunity.
Nevertheless, the CDC said, “For IVIG to modify disease in an active viral infectious process, early administration is likely required, and possibly prior to exposure,” and the treatment cannot be recommended.
Plasma exchange
Plasma exchange in combination with IVIG and corticosteroids was ineffective in a case series of four Argentinian children, although a single case published last year found that the combination was associated with significant improvement. However, there are not enough data to recommend this approach.
Fluoxetine
Fluoxetine’s antiviral potential turned up in a high-throughput screening project to identify novel compounds with antiviral efficacy against enteroviruses. In 2012, researchers from the University of California, Los Angeles, tested more than 1,000 compounds and found that the SSRI is a potent inhibitor of coxsackievirus. A later project at the National Institutes of Health replicated this finding, and determined that fluoxetine inhibited several enteroviruses, including the AFM suspect, EV-D68.
Fluoxetine concentrates more highly in the central nervous system than it does in plasma, but its antiviral properties have nothing to do with neurotransmitter activity. Rather, it appears to inhibit protein 2C, a highly conserved nonstructural protein that’s crucial to the assembly of RNA into virion particles.
In early November, a retrospective study examined fluoxetine’s use in 30 AFM patients, compared with 26 who did not receive it. The primary outcome was change in summative limb strength score. The study did little to clarify any benefit, however. The authors concluded that fluoxetine was preferentially given to patients with EDV-68 infections. They had more severe impairment at nadir, and at the last follow-up of about 1 year, they had worse outcomes.
“There is no clear human evidence for efficacy of fluoxetine in the treatment of AFM based on a single retrospective evaluation conducted in patients with AFM, and data from a mouse model also did not support efficacy,” the CDC said.
Antiviral medications
The CDC is quite clear on its recommendation that these drugs are not indicated in AFM, since it is not yet proven to be an infectious process.
“Any guidance regarding antiviral medications should be interpreted with great caution, given the unknowns about the pathogenesis of this illness at present ... Testing has been conducted at CDC for antiviral activity of compounds pleconaril, pocapavir, and vapendavir and none have significant activity against currently circulating strains of EV-D68 at clinically relevant concentrations.”
Interferon
There is some anecdotal evidence that interferon alpha-2b was beneficial in treating a polio-like syndrome associated with West Nile virus and Saint Louis encephalitis. “Although there are limited in vitro, animal, and anecdotal human data suggesting activity of some interferons against viral infections, sufficient data are lacking in the setting of AFM,” the agency said. “There is no indication that interferon should be used for the treatment of AFM, and there is concern about the potential for harm from the use of interferon given the immunomodulatory effects in the setting of possible ongoing viral replication.”
SOURCE: CDC Acute Flaccid Myelitis: Interim Considerations for Clinical Management
The updated guidance on managing acute flaccid myelitis is unlikely to relieve the frustrations of physicians struggling to treat the condition.
After reviewing the extant data on the baffling disorder, the Centers for Disease Control and Prevention found no evidence that corticosteroids, interferon, antivirals, or any other immunologic or biologic therapy is an effective treatment.
All of the treatments mentioned in the guidance have been used anecdotally, and often for cases proven to be associated with enterovirus-related cases. However, there are no well validated studies confirming benefit for any of these approaches, the agency said in its clinical management document.
Acute flaccid myelitis (AFM) has stricken 90 patients in the United States this year and another 252 cases are being investigated, according to new data from the CDC. The number of confirmed cases is triple that seen in 2017. Whether the disease is an infectious or autoimmune process, or something else entirely, remains unknown.
In response to the outbreak – the largest since 2014 – an expert panel of 4 CDC staff physicians reviewed the literature to find what, if any, treatments were effective; another 14 external experts provided input on the recommendations. At this point, nothing can be officially recommended, the agency said.
Corticosteroids
Corticosteroids should not be administered to most patients with AFM. In addition to “a theoretical concern” about the potential adverse effects of these drugs in acute infections, there is some hard evidence that they are associated with worse outcomes in enteroviral neuroinvasive diseases, particularly those caused by EV-71.
This observation, following a 2012 outbreak in Cambodia, led a World Health Organization commission to conclude that corticosteroids were contraindicated in the management of EV-71–associated neuroinvasive disease. This year, there has been an uptick in EV-A71-associated neurologic disease.
The CDC did hedge its advice on corticosteroids a bit in the setting of AFM, however. “There may be theoretical benefit for steroids in the setting of severe cord swelling or long tract signs suggesting white matter involvement, where steroids may salvage tissue that may be harmed due to an ongoing immune/inflammatory response. While AFM is clinically and radiographically defined by the predominance of gray matter damage in the spinal cord, some patients may have some white matter involvement. It is not clear if these different patterns are important relative to therapeutic considerations.”
Nevertheless, the agency does not recommend corticosteroid use for these patients. “The possible benefits of the use of corticosteroids to manage spinal cord edema or white matter involvement in AFM should be balanced with the possible harm due to immunosuppression in the setting of possible viral infection.”
IVIG
While IVIG holds some theoretical benefit for AFM, there are no high-level human data, the guidelines state. The treatment is generally safe and well tolerated, but the few reports of its use in AFM did not show clear benefit. These include two case series. One suggested an acute improvement of neurologic status, but no long-term resolution of deficits. The other indicated neither significant improvement nor deterioration.
However, current practice at Children’s Hospital of Philadelphia is to initiate IVIG therapy at AFM diagnosis in hopes of boosting humoral immunity.
Nevertheless, the CDC said, “For IVIG to modify disease in an active viral infectious process, early administration is likely required, and possibly prior to exposure,” and the treatment cannot be recommended.
Plasma exchange
Plasma exchange in combination with IVIG and corticosteroids was ineffective in a case series of four Argentinian children, although a single case published last year found that the combination was associated with significant improvement. However, there are not enough data to recommend this approach.
Fluoxetine
Fluoxetine’s antiviral potential turned up in a high-throughput screening project to identify novel compounds with antiviral efficacy against enteroviruses. In 2012, researchers from the University of California, Los Angeles, tested more than 1,000 compounds and found that the SSRI is a potent inhibitor of coxsackievirus. A later project at the National Institutes of Health replicated this finding, and determined that fluoxetine inhibited several enteroviruses, including the AFM suspect, EV-D68.
Fluoxetine concentrates more highly in the central nervous system than it does in plasma, but its antiviral properties have nothing to do with neurotransmitter activity. Rather, it appears to inhibit protein 2C, a highly conserved nonstructural protein that’s crucial to the assembly of RNA into virion particles.
In early November, a retrospective study examined fluoxetine’s use in 30 AFM patients, compared with 26 who did not receive it. The primary outcome was change in summative limb strength score. The study did little to clarify any benefit, however. The authors concluded that fluoxetine was preferentially given to patients with EDV-68 infections. They had more severe impairment at nadir, and at the last follow-up of about 1 year, they had worse outcomes.
“There is no clear human evidence for efficacy of fluoxetine in the treatment of AFM based on a single retrospective evaluation conducted in patients with AFM, and data from a mouse model also did not support efficacy,” the CDC said.
Antiviral medications
The CDC is quite clear on its recommendation that these drugs are not indicated in AFM, since it is not yet proven to be an infectious process.
“Any guidance regarding antiviral medications should be interpreted with great caution, given the unknowns about the pathogenesis of this illness at present ... Testing has been conducted at CDC for antiviral activity of compounds pleconaril, pocapavir, and vapendavir and none have significant activity against currently circulating strains of EV-D68 at clinically relevant concentrations.”
Interferon
There is some anecdotal evidence that interferon alpha-2b was beneficial in treating a polio-like syndrome associated with West Nile virus and Saint Louis encephalitis. “Although there are limited in vitro, animal, and anecdotal human data suggesting activity of some interferons against viral infections, sufficient data are lacking in the setting of AFM,” the agency said. “There is no indication that interferon should be used for the treatment of AFM, and there is concern about the potential for harm from the use of interferon given the immunomodulatory effects in the setting of possible ongoing viral replication.”
SOURCE: CDC Acute Flaccid Myelitis: Interim Considerations for Clinical Management
The updated guidance on managing acute flaccid myelitis is unlikely to relieve the frustrations of physicians struggling to treat the condition.
After reviewing the extant data on the baffling disorder, the Centers for Disease Control and Prevention found no evidence that corticosteroids, interferon, antivirals, or any other immunologic or biologic therapy is an effective treatment.
All of the treatments mentioned in the guidance have been used anecdotally, and often for cases proven to be associated with enterovirus-related cases. However, there are no well validated studies confirming benefit for any of these approaches, the agency said in its clinical management document.
Acute flaccid myelitis (AFM) has stricken 90 patients in the United States this year and another 252 cases are being investigated, according to new data from the CDC. The number of confirmed cases is triple that seen in 2017. Whether the disease is an infectious or autoimmune process, or something else entirely, remains unknown.
In response to the outbreak – the largest since 2014 – an expert panel of 4 CDC staff physicians reviewed the literature to find what, if any, treatments were effective; another 14 external experts provided input on the recommendations. At this point, nothing can be officially recommended, the agency said.
Corticosteroids
Corticosteroids should not be administered to most patients with AFM. In addition to “a theoretical concern” about the potential adverse effects of these drugs in acute infections, there is some hard evidence that they are associated with worse outcomes in enteroviral neuroinvasive diseases, particularly those caused by EV-71.
This observation, following a 2012 outbreak in Cambodia, led a World Health Organization commission to conclude that corticosteroids were contraindicated in the management of EV-71–associated neuroinvasive disease. This year, there has been an uptick in EV-A71-associated neurologic disease.
The CDC did hedge its advice on corticosteroids a bit in the setting of AFM, however. “There may be theoretical benefit for steroids in the setting of severe cord swelling or long tract signs suggesting white matter involvement, where steroids may salvage tissue that may be harmed due to an ongoing immune/inflammatory response. While AFM is clinically and radiographically defined by the predominance of gray matter damage in the spinal cord, some patients may have some white matter involvement. It is not clear if these different patterns are important relative to therapeutic considerations.”
Nevertheless, the agency does not recommend corticosteroid use for these patients. “The possible benefits of the use of corticosteroids to manage spinal cord edema or white matter involvement in AFM should be balanced with the possible harm due to immunosuppression in the setting of possible viral infection.”
IVIG
While IVIG holds some theoretical benefit for AFM, there are no high-level human data, the guidelines state. The treatment is generally safe and well tolerated, but the few reports of its use in AFM did not show clear benefit. These include two case series. One suggested an acute improvement of neurologic status, but no long-term resolution of deficits. The other indicated neither significant improvement nor deterioration.
However, current practice at Children’s Hospital of Philadelphia is to initiate IVIG therapy at AFM diagnosis in hopes of boosting humoral immunity.
Nevertheless, the CDC said, “For IVIG to modify disease in an active viral infectious process, early administration is likely required, and possibly prior to exposure,” and the treatment cannot be recommended.
Plasma exchange
Plasma exchange in combination with IVIG and corticosteroids was ineffective in a case series of four Argentinian children, although a single case published last year found that the combination was associated with significant improvement. However, there are not enough data to recommend this approach.
Fluoxetine
Fluoxetine’s antiviral potential turned up in a high-throughput screening project to identify novel compounds with antiviral efficacy against enteroviruses. In 2012, researchers from the University of California, Los Angeles, tested more than 1,000 compounds and found that the SSRI is a potent inhibitor of coxsackievirus. A later project at the National Institutes of Health replicated this finding, and determined that fluoxetine inhibited several enteroviruses, including the AFM suspect, EV-D68.
Fluoxetine concentrates more highly in the central nervous system than it does in plasma, but its antiviral properties have nothing to do with neurotransmitter activity. Rather, it appears to inhibit protein 2C, a highly conserved nonstructural protein that’s crucial to the assembly of RNA into virion particles.
In early November, a retrospective study examined fluoxetine’s use in 30 AFM patients, compared with 26 who did not receive it. The primary outcome was change in summative limb strength score. The study did little to clarify any benefit, however. The authors concluded that fluoxetine was preferentially given to patients with EDV-68 infections. They had more severe impairment at nadir, and at the last follow-up of about 1 year, they had worse outcomes.
“There is no clear human evidence for efficacy of fluoxetine in the treatment of AFM based on a single retrospective evaluation conducted in patients with AFM, and data from a mouse model also did not support efficacy,” the CDC said.
Antiviral medications
The CDC is quite clear on its recommendation that these drugs are not indicated in AFM, since it is not yet proven to be an infectious process.
“Any guidance regarding antiviral medications should be interpreted with great caution, given the unknowns about the pathogenesis of this illness at present ... Testing has been conducted at CDC for antiviral activity of compounds pleconaril, pocapavir, and vapendavir and none have significant activity against currently circulating strains of EV-D68 at clinically relevant concentrations.”
Interferon
There is some anecdotal evidence that interferon alpha-2b was beneficial in treating a polio-like syndrome associated with West Nile virus and Saint Louis encephalitis. “Although there are limited in vitro, animal, and anecdotal human data suggesting activity of some interferons against viral infections, sufficient data are lacking in the setting of AFM,” the agency said. “There is no indication that interferon should be used for the treatment of AFM, and there is concern about the potential for harm from the use of interferon given the immunomodulatory effects in the setting of possible ongoing viral replication.”
SOURCE: CDC Acute Flaccid Myelitis: Interim Considerations for Clinical Management
Conference News Roundup—American Association of Neuromuscular & Electrodiagnostic Medicine
Does Thymectomy Benefit Patients With Anti-MuSK Myasthenia Gravis?
Among patients with anti-muscle-specific kinase (MuSK) myasthenia gravis, thymectomy is not associated with greater likelihood of clinical improvement, according to an analysis of data from a multicenter cohort study.
Although a randomized trial has demonstrated benefit from thymectomy in nonthymomatous antiacetylcholine receptor (AChR) antibody positive generalized myasthenia gravis, observational studies suggest that thymectomy may not be efficacious in anti-MuSK myasthenia gravis. Histologic studies have found that patients with anti-MuSK myasthenia gravis have less hyperplastic thymic tissue, compared with patients with anti-AChR myasthenia gravis.
To evaluate the therapeutic impact of thymectomy in patients with anti-MuSK myasthenia gravis, Katherine Clifford, a medical student at the University of Vermont Larner College of Medicine in Burlington, and colleagues analyzed data from a multicenter, retrospective, blinded review of rituximab treatment in patients with anti-MuSK myasthenia gravis. The primary outcome was favorable outcome on the Myasthenia Gravis Foundation of America (MGFA) Post-Intervention Status (PIS). The researchers defined a favorable outcome as an MGFA PIS score of minimal manifestations or better.
Secondary outcomes included prednisone dose; use of other immunosuppressant medications, IV immunoglobulin (IVIG), or plasma exchange (PLEX) treatment; and Myasthenia Gravis Status and Treatment Intensity (MGSTI).
Baseline characteristics were similar between patients with anti-MuSK myasthenia gravis who received thymectomy (n = 26) and those who did not (n = 29), including treatment with rituximab (42% vs 45%). Median follow-up was more than three years.
At last visit, 35% (nine of 26) of patients who received thymectomy had a favorable outcome, compared with 55% (16 of 29) of patients who did not receive thymectomy. In addition, 69% of patients who received thymectomy were taking prednisone, compared with 41% of patients who did not receive thymectomy (median dose, 10 mg/day vs 0 mg/day).
“After controlling for rituximab, baseline prednisone, and final IVIG/PLEX treatment, thymectomy was not associated with greater likelihood of favorable clinical outcome, but broad confidence intervals cannot exclude therapeutic effect (odds ratio, 0.43),” the investigators reported.
“The recent MGTX trial clearly demonstrated the benefit of thymectomy for patients with AChR antibody positive myasthenia gravis,” said A. Gordon Smith, MD, Cochair of the AANEM Annual Meeting Program Committee. “Ms. Clifford and her colleagues now provide compelling data suggesting thymectomy may not be effective in MuSK-positive myasthenia gravis.”
The study’s follow-up is long enough for the findings to be clinically “relevant to all physicians treating myasthenia gravis,” said Robert W. Irwin, MD, Cochair of the AANEM Annual Meeting Program Committee.
What Are the Clinical, Laboratory, and Electrodiagnostic Features of Zinc Deficiency-InducedPeripheral Neuropathy?
Patients with zinc deficiency-induced peripheral neuropathy may present with paresthesia, gait abnormalities, sensory deficits, reduced tendon reflexes, an abnormal Romberg test, and increased CSF protein, according to a study.
Recognition of the features of zinc deficiency-induced peripheral neuropathy may help neurologists diagnose the disorder and manage patients, researchers said.
“Zinc, an essential trace element, plays a critical role in maintaining normal structural and functional conditions in the body,” said lead author Favio C. Bumanlag, Chief Technologist in the Department of Neurology at the Lewis Katz School of Medicine at Temple University in Philadelphia. “Peripheral nerves are susceptible to damage when zinc deficiency occurs.... Recognition of [zinc deficiency-induced peripheral neuropathy] will help physicians and technologists effectively manage patients.”
To study the clinical and electrophysiologic features of zinc deficiency-induced peripheral neuropathy, Mr. Bumanlag and Jin Luo, MD, PhD, Professor of Neurology and Pharmacology at Temple University, retrospectively reviewed charts in their neuromuscular clinic and EMG laboratory database to identify patients with peripheral neuropathy and zinc deficiency. They included charts from between January 1, 2015, and December 31, 2017, in their review. They excluded patients with abnormal copper levels.
Mr. Bumanlag and Dr. Luo obtained information about patients’ clinical presentations, past medical histories, BMI, neurologic examinations, and laboratory results. They also examined patients’ needle electromyograms and nerve conduction studies.
In all, they identified 12 patients with peripheral neuropathy and zinc deficiency. Patients had a mean age of 55.1. Six were female. Patients’ mean zinc level was 52.5 μg/dL, with a range of 37 μg/dL to 58 μg/dL (reference, 56–134 μg/dL). Mean copper level was 107.6 μg/dL, with a range of 84 μg/dL to 173 μg/dL (reference, 72–166
Notable findings in presentation included paresthesia in 75 and gait abnormalities in 42%. One patient was obese (8%), and three patients had diarrhea (25%). Neurologic examination showed sensory deficits in 83%, reduced tendon reflexes in 67%, and an abnormal Romberg test in 67%. Four of five patients had increased CSF protein. Electrophysiologic evaluations showed features of demyelinating peripheral neuropathy (28%) and distally active denervation in the lower extremities.
“Zinc participates in more than 200 enzymatic reactions,” said the researchers. “Unfortunately, zinc deficiency-induced peripheral neuropathy is often misdiagnosed or delayed in diagnosis. Literature on zinc deficiency-induced peripheral neuropathy is sparse.”
Disability in Patients With Stiff Person Syndrome May Progress Faster Than Thought
Stiff person syndrome leads to disability if therapy is not initiated early in the disease course, according to a prospective study. In addition, patients with stiff person syndrome may have “faster progression of disablement than originally reported and believed,” said lead study author Goran Rakocevic, MD. Dr. Rakocevic is Associate Professor of Neurology, Director of the Neuromuscular Electrodiagnostic Laboratory, Clinical Director of the Jefferson Weinberg ALS Center, and Director of the Neuromuscular Medicine Fellowship Program at Thomas Jefferson University in Philadelphia.
Stiff person syndrome is a disorder characterized by muscle rigidity and episodic spasms in axial and limb musculature, as well as heightened sensitivity to external stimuli. To describe the natural history of stiff person syndrome, the extent of accumulated disability, and associated clinical features, Dr. Rakocevic and his research colleagues conducted a prospective cohort study in patients followed for up to eight years in a single center.
The cohort included 57 patients with mean age at disease onset of 42 (range, 22 to 60). Of these, 32 patients were examined every six months for two years without receiving immune therapies. The investigators assessed disease progression using quantitative scales of stiffness and heightened sensitivity.
Patients’ most frequent initial symptoms were leg stiffness, paraspinal muscle rigidity, and painful spasms. Although no patients required assistance for ambulation during the first two years of the disease, 46 patients (80%) lost the ability to walk independently during follow-up, despite symptomatic medications. In the longitudinal cohort, the number of stiff areas increased, which was consistent with worsening functional status and quality of life. The researchers confirmed a strong association between stiff person syndrome and the HLA-DR and DQ haplotypes.
The study is the largest prospective study of patients with stiff person syndrome and the first to provide longitudinal data on the natural course of the disorder in a large patient subgroup using objective clinical measures, Dr. Rakocevic and colleagues said. “The study shows that stiff person syndrome is a progressive autoimmune disease that leads to disability if ... immunotherapy is not applied,” said the investigators.
“Early diagnosis and management of stiff person syndrome can be challenging,” said A. Gordon Smith, MD, Cochair of the AANEM Annual Meeting Program Committee. The study by Dr. Rakocevic’s team demonstrates “that stiff person syndrome causes progressive stiffness and functional decline, with 80% [of patients] becoming unable to walk independently,” he said. “Their research emphasizes the need to treat early and will help clinicians recognize stiff person syndrome earlier in its course.”
The study adds to neurologists’ understanding of the rare disorder, and its strengths include the length of follow-up and the number of patients, said Robert W. Irwin, MD, Cochair of the AANEM Annual Meeting Program Committee.
Does Thymectomy Benefit Patients With Anti-MuSK Myasthenia Gravis?
Among patients with anti-muscle-specific kinase (MuSK) myasthenia gravis, thymectomy is not associated with greater likelihood of clinical improvement, according to an analysis of data from a multicenter cohort study.
Although a randomized trial has demonstrated benefit from thymectomy in nonthymomatous antiacetylcholine receptor (AChR) antibody positive generalized myasthenia gravis, observational studies suggest that thymectomy may not be efficacious in anti-MuSK myasthenia gravis. Histologic studies have found that patients with anti-MuSK myasthenia gravis have less hyperplastic thymic tissue, compared with patients with anti-AChR myasthenia gravis.
To evaluate the therapeutic impact of thymectomy in patients with anti-MuSK myasthenia gravis, Katherine Clifford, a medical student at the University of Vermont Larner College of Medicine in Burlington, and colleagues analyzed data from a multicenter, retrospective, blinded review of rituximab treatment in patients with anti-MuSK myasthenia gravis. The primary outcome was favorable outcome on the Myasthenia Gravis Foundation of America (MGFA) Post-Intervention Status (PIS). The researchers defined a favorable outcome as an MGFA PIS score of minimal manifestations or better.
Secondary outcomes included prednisone dose; use of other immunosuppressant medications, IV immunoglobulin (IVIG), or plasma exchange (PLEX) treatment; and Myasthenia Gravis Status and Treatment Intensity (MGSTI).
Baseline characteristics were similar between patients with anti-MuSK myasthenia gravis who received thymectomy (n = 26) and those who did not (n = 29), including treatment with rituximab (42% vs 45%). Median follow-up was more than three years.
At last visit, 35% (nine of 26) of patients who received thymectomy had a favorable outcome, compared with 55% (16 of 29) of patients who did not receive thymectomy. In addition, 69% of patients who received thymectomy were taking prednisone, compared with 41% of patients who did not receive thymectomy (median dose, 10 mg/day vs 0 mg/day).
“After controlling for rituximab, baseline prednisone, and final IVIG/PLEX treatment, thymectomy was not associated with greater likelihood of favorable clinical outcome, but broad confidence intervals cannot exclude therapeutic effect (odds ratio, 0.43),” the investigators reported.
“The recent MGTX trial clearly demonstrated the benefit of thymectomy for patients with AChR antibody positive myasthenia gravis,” said A. Gordon Smith, MD, Cochair of the AANEM Annual Meeting Program Committee. “Ms. Clifford and her colleagues now provide compelling data suggesting thymectomy may not be effective in MuSK-positive myasthenia gravis.”
The study’s follow-up is long enough for the findings to be clinically “relevant to all physicians treating myasthenia gravis,” said Robert W. Irwin, MD, Cochair of the AANEM Annual Meeting Program Committee.
What Are the Clinical, Laboratory, and Electrodiagnostic Features of Zinc Deficiency-InducedPeripheral Neuropathy?
Patients with zinc deficiency-induced peripheral neuropathy may present with paresthesia, gait abnormalities, sensory deficits, reduced tendon reflexes, an abnormal Romberg test, and increased CSF protein, according to a study.
Recognition of the features of zinc deficiency-induced peripheral neuropathy may help neurologists diagnose the disorder and manage patients, researchers said.
“Zinc, an essential trace element, plays a critical role in maintaining normal structural and functional conditions in the body,” said lead author Favio C. Bumanlag, Chief Technologist in the Department of Neurology at the Lewis Katz School of Medicine at Temple University in Philadelphia. “Peripheral nerves are susceptible to damage when zinc deficiency occurs.... Recognition of [zinc deficiency-induced peripheral neuropathy] will help physicians and technologists effectively manage patients.”
To study the clinical and electrophysiologic features of zinc deficiency-induced peripheral neuropathy, Mr. Bumanlag and Jin Luo, MD, PhD, Professor of Neurology and Pharmacology at Temple University, retrospectively reviewed charts in their neuromuscular clinic and EMG laboratory database to identify patients with peripheral neuropathy and zinc deficiency. They included charts from between January 1, 2015, and December 31, 2017, in their review. They excluded patients with abnormal copper levels.
Mr. Bumanlag and Dr. Luo obtained information about patients’ clinical presentations, past medical histories, BMI, neurologic examinations, and laboratory results. They also examined patients’ needle electromyograms and nerve conduction studies.
In all, they identified 12 patients with peripheral neuropathy and zinc deficiency. Patients had a mean age of 55.1. Six were female. Patients’ mean zinc level was 52.5 μg/dL, with a range of 37 μg/dL to 58 μg/dL (reference, 56–134 μg/dL). Mean copper level was 107.6 μg/dL, with a range of 84 μg/dL to 173 μg/dL (reference, 72–166
Notable findings in presentation included paresthesia in 75 and gait abnormalities in 42%. One patient was obese (8%), and three patients had diarrhea (25%). Neurologic examination showed sensory deficits in 83%, reduced tendon reflexes in 67%, and an abnormal Romberg test in 67%. Four of five patients had increased CSF protein. Electrophysiologic evaluations showed features of demyelinating peripheral neuropathy (28%) and distally active denervation in the lower extremities.
“Zinc participates in more than 200 enzymatic reactions,” said the researchers. “Unfortunately, zinc deficiency-induced peripheral neuropathy is often misdiagnosed or delayed in diagnosis. Literature on zinc deficiency-induced peripheral neuropathy is sparse.”
Disability in Patients With Stiff Person Syndrome May Progress Faster Than Thought
Stiff person syndrome leads to disability if therapy is not initiated early in the disease course, according to a prospective study. In addition, patients with stiff person syndrome may have “faster progression of disablement than originally reported and believed,” said lead study author Goran Rakocevic, MD. Dr. Rakocevic is Associate Professor of Neurology, Director of the Neuromuscular Electrodiagnostic Laboratory, Clinical Director of the Jefferson Weinberg ALS Center, and Director of the Neuromuscular Medicine Fellowship Program at Thomas Jefferson University in Philadelphia.
Stiff person syndrome is a disorder characterized by muscle rigidity and episodic spasms in axial and limb musculature, as well as heightened sensitivity to external stimuli. To describe the natural history of stiff person syndrome, the extent of accumulated disability, and associated clinical features, Dr. Rakocevic and his research colleagues conducted a prospective cohort study in patients followed for up to eight years in a single center.
The cohort included 57 patients with mean age at disease onset of 42 (range, 22 to 60). Of these, 32 patients were examined every six months for two years without receiving immune therapies. The investigators assessed disease progression using quantitative scales of stiffness and heightened sensitivity.
Patients’ most frequent initial symptoms were leg stiffness, paraspinal muscle rigidity, and painful spasms. Although no patients required assistance for ambulation during the first two years of the disease, 46 patients (80%) lost the ability to walk independently during follow-up, despite symptomatic medications. In the longitudinal cohort, the number of stiff areas increased, which was consistent with worsening functional status and quality of life. The researchers confirmed a strong association between stiff person syndrome and the HLA-DR and DQ haplotypes.
The study is the largest prospective study of patients with stiff person syndrome and the first to provide longitudinal data on the natural course of the disorder in a large patient subgroup using objective clinical measures, Dr. Rakocevic and colleagues said. “The study shows that stiff person syndrome is a progressive autoimmune disease that leads to disability if ... immunotherapy is not applied,” said the investigators.
“Early diagnosis and management of stiff person syndrome can be challenging,” said A. Gordon Smith, MD, Cochair of the AANEM Annual Meeting Program Committee. The study by Dr. Rakocevic’s team demonstrates “that stiff person syndrome causes progressive stiffness and functional decline, with 80% [of patients] becoming unable to walk independently,” he said. “Their research emphasizes the need to treat early and will help clinicians recognize stiff person syndrome earlier in its course.”
The study adds to neurologists’ understanding of the rare disorder, and its strengths include the length of follow-up and the number of patients, said Robert W. Irwin, MD, Cochair of the AANEM Annual Meeting Program Committee.
Does Thymectomy Benefit Patients With Anti-MuSK Myasthenia Gravis?
Among patients with anti-muscle-specific kinase (MuSK) myasthenia gravis, thymectomy is not associated with greater likelihood of clinical improvement, according to an analysis of data from a multicenter cohort study.
Although a randomized trial has demonstrated benefit from thymectomy in nonthymomatous antiacetylcholine receptor (AChR) antibody positive generalized myasthenia gravis, observational studies suggest that thymectomy may not be efficacious in anti-MuSK myasthenia gravis. Histologic studies have found that patients with anti-MuSK myasthenia gravis have less hyperplastic thymic tissue, compared with patients with anti-AChR myasthenia gravis.
To evaluate the therapeutic impact of thymectomy in patients with anti-MuSK myasthenia gravis, Katherine Clifford, a medical student at the University of Vermont Larner College of Medicine in Burlington, and colleagues analyzed data from a multicenter, retrospective, blinded review of rituximab treatment in patients with anti-MuSK myasthenia gravis. The primary outcome was favorable outcome on the Myasthenia Gravis Foundation of America (MGFA) Post-Intervention Status (PIS). The researchers defined a favorable outcome as an MGFA PIS score of minimal manifestations or better.
Secondary outcomes included prednisone dose; use of other immunosuppressant medications, IV immunoglobulin (IVIG), or plasma exchange (PLEX) treatment; and Myasthenia Gravis Status and Treatment Intensity (MGSTI).
Baseline characteristics were similar between patients with anti-MuSK myasthenia gravis who received thymectomy (n = 26) and those who did not (n = 29), including treatment with rituximab (42% vs 45%). Median follow-up was more than three years.
At last visit, 35% (nine of 26) of patients who received thymectomy had a favorable outcome, compared with 55% (16 of 29) of patients who did not receive thymectomy. In addition, 69% of patients who received thymectomy were taking prednisone, compared with 41% of patients who did not receive thymectomy (median dose, 10 mg/day vs 0 mg/day).
“After controlling for rituximab, baseline prednisone, and final IVIG/PLEX treatment, thymectomy was not associated with greater likelihood of favorable clinical outcome, but broad confidence intervals cannot exclude therapeutic effect (odds ratio, 0.43),” the investigators reported.
“The recent MGTX trial clearly demonstrated the benefit of thymectomy for patients with AChR antibody positive myasthenia gravis,” said A. Gordon Smith, MD, Cochair of the AANEM Annual Meeting Program Committee. “Ms. Clifford and her colleagues now provide compelling data suggesting thymectomy may not be effective in MuSK-positive myasthenia gravis.”
The study’s follow-up is long enough for the findings to be clinically “relevant to all physicians treating myasthenia gravis,” said Robert W. Irwin, MD, Cochair of the AANEM Annual Meeting Program Committee.
What Are the Clinical, Laboratory, and Electrodiagnostic Features of Zinc Deficiency-InducedPeripheral Neuropathy?
Patients with zinc deficiency-induced peripheral neuropathy may present with paresthesia, gait abnormalities, sensory deficits, reduced tendon reflexes, an abnormal Romberg test, and increased CSF protein, according to a study.
Recognition of the features of zinc deficiency-induced peripheral neuropathy may help neurologists diagnose the disorder and manage patients, researchers said.
“Zinc, an essential trace element, plays a critical role in maintaining normal structural and functional conditions in the body,” said lead author Favio C. Bumanlag, Chief Technologist in the Department of Neurology at the Lewis Katz School of Medicine at Temple University in Philadelphia. “Peripheral nerves are susceptible to damage when zinc deficiency occurs.... Recognition of [zinc deficiency-induced peripheral neuropathy] will help physicians and technologists effectively manage patients.”
To study the clinical and electrophysiologic features of zinc deficiency-induced peripheral neuropathy, Mr. Bumanlag and Jin Luo, MD, PhD, Professor of Neurology and Pharmacology at Temple University, retrospectively reviewed charts in their neuromuscular clinic and EMG laboratory database to identify patients with peripheral neuropathy and zinc deficiency. They included charts from between January 1, 2015, and December 31, 2017, in their review. They excluded patients with abnormal copper levels.
Mr. Bumanlag and Dr. Luo obtained information about patients’ clinical presentations, past medical histories, BMI, neurologic examinations, and laboratory results. They also examined patients’ needle electromyograms and nerve conduction studies.
In all, they identified 12 patients with peripheral neuropathy and zinc deficiency. Patients had a mean age of 55.1. Six were female. Patients’ mean zinc level was 52.5 μg/dL, with a range of 37 μg/dL to 58 μg/dL (reference, 56–134 μg/dL). Mean copper level was 107.6 μg/dL, with a range of 84 μg/dL to 173 μg/dL (reference, 72–166
Notable findings in presentation included paresthesia in 75 and gait abnormalities in 42%. One patient was obese (8%), and three patients had diarrhea (25%). Neurologic examination showed sensory deficits in 83%, reduced tendon reflexes in 67%, and an abnormal Romberg test in 67%. Four of five patients had increased CSF protein. Electrophysiologic evaluations showed features of demyelinating peripheral neuropathy (28%) and distally active denervation in the lower extremities.
“Zinc participates in more than 200 enzymatic reactions,” said the researchers. “Unfortunately, zinc deficiency-induced peripheral neuropathy is often misdiagnosed or delayed in diagnosis. Literature on zinc deficiency-induced peripheral neuropathy is sparse.”
Disability in Patients With Stiff Person Syndrome May Progress Faster Than Thought
Stiff person syndrome leads to disability if therapy is not initiated early in the disease course, according to a prospective study. In addition, patients with stiff person syndrome may have “faster progression of disablement than originally reported and believed,” said lead study author Goran Rakocevic, MD. Dr. Rakocevic is Associate Professor of Neurology, Director of the Neuromuscular Electrodiagnostic Laboratory, Clinical Director of the Jefferson Weinberg ALS Center, and Director of the Neuromuscular Medicine Fellowship Program at Thomas Jefferson University in Philadelphia.
Stiff person syndrome is a disorder characterized by muscle rigidity and episodic spasms in axial and limb musculature, as well as heightened sensitivity to external stimuli. To describe the natural history of stiff person syndrome, the extent of accumulated disability, and associated clinical features, Dr. Rakocevic and his research colleagues conducted a prospective cohort study in patients followed for up to eight years in a single center.
The cohort included 57 patients with mean age at disease onset of 42 (range, 22 to 60). Of these, 32 patients were examined every six months for two years without receiving immune therapies. The investigators assessed disease progression using quantitative scales of stiffness and heightened sensitivity.
Patients’ most frequent initial symptoms were leg stiffness, paraspinal muscle rigidity, and painful spasms. Although no patients required assistance for ambulation during the first two years of the disease, 46 patients (80%) lost the ability to walk independently during follow-up, despite symptomatic medications. In the longitudinal cohort, the number of stiff areas increased, which was consistent with worsening functional status and quality of life. The researchers confirmed a strong association between stiff person syndrome and the HLA-DR and DQ haplotypes.
The study is the largest prospective study of patients with stiff person syndrome and the first to provide longitudinal data on the natural course of the disorder in a large patient subgroup using objective clinical measures, Dr. Rakocevic and colleagues said. “The study shows that stiff person syndrome is a progressive autoimmune disease that leads to disability if ... immunotherapy is not applied,” said the investigators.
“Early diagnosis and management of stiff person syndrome can be challenging,” said A. Gordon Smith, MD, Cochair of the AANEM Annual Meeting Program Committee. The study by Dr. Rakocevic’s team demonstrates “that stiff person syndrome causes progressive stiffness and functional decline, with 80% [of patients] becoming unable to walk independently,” he said. “Their research emphasizes the need to treat early and will help clinicians recognize stiff person syndrome earlier in its course.”
The study adds to neurologists’ understanding of the rare disorder, and its strengths include the length of follow-up and the number of patients, said Robert W. Irwin, MD, Cochair of the AANEM Annual Meeting Program Committee.
Does Thymectomy Benefit Patients With Anti-MuSK Myasthenia Gravis?
Favorable clinical outcomes are not more likely in patients with anti-MuSK myasthenia gravis who undergo thymectomy versus patients who do not.
WASHINGTON, DC—Among patients with anti-muscle-specific kinase (MuSK) myasthenia gravis, thymectomy is not associated with greater likelihood of clinical improvement, according to an analysis of data from a multicenter cohort study. The results were presented at the 2018 Annual Meeting of the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM).
Although a randomized trial has demonstrated benefit from thymectomy in nonthymomatous antiacetylcholine receptor (AChR) antibody positive generalized myasthenia gravis, observational studies suggest that thymectomy may not be efficacious in anti-MuSK myasthenia gravis. Histologic studies have found that patients with anti-MuSK myasthenia gravis have less hyperplastic thymic tissue, compared with patients with anti-AChR myasthenia gravis.
To evaluate the therapeutic impact of thymectomy in patients with anti-MuSK myasthenia gravis, Katherine Clifford, a medical student at the University of Vermont Larner College of Medicine in Burlington, and colleagues analyzed data from a multicenter, retrospective, blinded review of rituximab treatment in patients with anti-MuSK myasthenia gravis. The primary outcome was favorable outcome on the Myasthenia Gravis Foundation of America (MGFA) Post-Intervention Status (PIS). The researchers defined a favorable outcome as an MGFA PIS score of minimal manifestations or better.
Secondary outcomes included prednisone dose; use of other immunosuppressant medications, IV immunoglobulin (IVIG), or plasma exchange (PLEX) treatment; and Myasthenia Gravis Status and Treatment Intensity (MGSTI).
Baseline characteristics were similar between patients with anti-MuSK myasthenia gravis who underwent thymectomy (n = 26) and those who did not (n = 29), including treatment with rituximab (42% vs 45%). Median follow-up was more than three years.
At last visit, 35% (nine of 26) of patients who underwent thymectomy had a favorable outcome, compared with 55% (16 of 29) of patients who did not undergo thymectomy. In addition, 69% of patients who underwent thymectomy were taking prednisone, compared with 41% of patients who did not undergo thymectomy (median dose, 10 mg/day vs 0 mg/day).
“After controlling for rituximab, baseline prednisone, and final IVIG/PLEX treatment, thymectomy was not associated with greater likelihood of favorable clinical outcome, but broad confidence intervals cannot exclude therapeutic effect (odds ratio, 0.43),” the investigators reported. 
“The recent MGTX trial clearly demonstrated the benefit of thymectomy for patients with AChR antibody positive myasthenia gravis,” said A. Gordon Smith, MD, Cochair of the AANEM Annual Meeting Program Committee. “Ms. Clifford and her colleagues now provide compelling data suggesting thymectomy may not be effective in MuSK-positive myasthenia gravis.”
The study’s follow-up is long enough for the findings to be clinically “relevant to all physicians treating myasthenia gravis,” said Robert W. Irwin, MD, Cochair of the AANEM Annual Meeting Program Committee.
Favorable clinical outcomes are not more likely in patients with anti-MuSK myasthenia gravis who undergo thymectomy versus patients who do not.
Favorable clinical outcomes are not more likely in patients with anti-MuSK myasthenia gravis who undergo thymectomy versus patients who do not.
WASHINGTON, DC—Among patients with anti-muscle-specific kinase (MuSK) myasthenia gravis, thymectomy is not associated with greater likelihood of clinical improvement, according to an analysis of data from a multicenter cohort study. The results were presented at the 2018 Annual Meeting of the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM).
Although a randomized trial has demonstrated benefit from thymectomy in nonthymomatous antiacetylcholine receptor (AChR) antibody positive generalized myasthenia gravis, observational studies suggest that thymectomy may not be efficacious in anti-MuSK myasthenia gravis. Histologic studies have found that patients with anti-MuSK myasthenia gravis have less hyperplastic thymic tissue, compared with patients with anti-AChR myasthenia gravis.
To evaluate the therapeutic impact of thymectomy in patients with anti-MuSK myasthenia gravis, Katherine Clifford, a medical student at the University of Vermont Larner College of Medicine in Burlington, and colleagues analyzed data from a multicenter, retrospective, blinded review of rituximab treatment in patients with anti-MuSK myasthenia gravis. The primary outcome was favorable outcome on the Myasthenia Gravis Foundation of America (MGFA) Post-Intervention Status (PIS). The researchers defined a favorable outcome as an MGFA PIS score of minimal manifestations or better.
Secondary outcomes included prednisone dose; use of other immunosuppressant medications, IV immunoglobulin (IVIG), or plasma exchange (PLEX) treatment; and Myasthenia Gravis Status and Treatment Intensity (MGSTI).
Baseline characteristics were similar between patients with anti-MuSK myasthenia gravis who underwent thymectomy (n = 26) and those who did not (n = 29), including treatment with rituximab (42% vs 45%). Median follow-up was more than three years.
At last visit, 35% (nine of 26) of patients who underwent thymectomy had a favorable outcome, compared with 55% (16 of 29) of patients who did not undergo thymectomy. In addition, 69% of patients who underwent thymectomy were taking prednisone, compared with 41% of patients who did not undergo thymectomy (median dose, 10 mg/day vs 0 mg/day).
“After controlling for rituximab, baseline prednisone, and final IVIG/PLEX treatment, thymectomy was not associated with greater likelihood of favorable clinical outcome, but broad confidence intervals cannot exclude therapeutic effect (odds ratio, 0.43),” the investigators reported.
“The recent MGTX trial clearly demonstrated the benefit of thymectomy for patients with AChR antibody positive myasthenia gravis,” said A. Gordon Smith, MD, Cochair of the AANEM Annual Meeting Program Committee. “Ms. Clifford and her colleagues now provide compelling data suggesting thymectomy may not be effective in MuSK-positive myasthenia gravis.”
The study’s follow-up is long enough for the findings to be clinically “relevant to all physicians treating myasthenia gravis,” said Robert W. Irwin, MD, Cochair of the AANEM Annual Meeting Program Committee.
WASHINGTON, DC—Among patients with anti-muscle-specific kinase (MuSK) myasthenia gravis, thymectomy is not associated with greater likelihood of clinical improvement, according to an analysis of data from a multicenter cohort study. The results were presented at the 2018 Annual Meeting of the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM).
Although a randomized trial has demonstrated benefit from thymectomy in nonthymomatous antiacetylcholine receptor (AChR) antibody positive generalized myasthenia gravis, observational studies suggest that thymectomy may not be efficacious in anti-MuSK myasthenia gravis. Histologic studies have found that patients with anti-MuSK myasthenia gravis have less hyperplastic thymic tissue, compared with patients with anti-AChR myasthenia gravis.
To evaluate the therapeutic impact of thymectomy in patients with anti-MuSK myasthenia gravis, Katherine Clifford, a medical student at the University of Vermont Larner College of Medicine in Burlington, and colleagues analyzed data from a multicenter, retrospective, blinded review of rituximab treatment in patients with anti-MuSK myasthenia gravis. The primary outcome was favorable outcome on the Myasthenia Gravis Foundation of America (MGFA) Post-Intervention Status (PIS). The researchers defined a favorable outcome as an MGFA PIS score of minimal manifestations or better.
Secondary outcomes included prednisone dose; use of other immunosuppressant medications, IV immunoglobulin (IVIG), or plasma exchange (PLEX) treatment; and Myasthenia Gravis Status and Treatment Intensity (MGSTI).
Baseline characteristics were similar between patients with anti-MuSK myasthenia gravis who underwent thymectomy (n = 26) and those who did not (n = 29), including treatment with rituximab (42% vs 45%). Median follow-up was more than three years.
At last visit, 35% (nine of 26) of patients who underwent thymectomy had a favorable outcome, compared with 55% (16 of 29) of patients who did not undergo thymectomy. In addition, 69% of patients who underwent thymectomy were taking prednisone, compared with 41% of patients who did not undergo thymectomy (median dose, 10 mg/day vs 0 mg/day).
“After controlling for rituximab, baseline prednisone, and final IVIG/PLEX treatment, thymectomy was not associated with greater likelihood of favorable clinical outcome, but broad confidence intervals cannot exclude therapeutic effect (odds ratio, 0.43),” the investigators reported.
“The recent MGTX trial clearly demonstrated the benefit of thymectomy for patients with AChR antibody positive myasthenia gravis,” said A. Gordon Smith, MD, Cochair of the AANEM Annual Meeting Program Committee. “Ms. Clifford and her colleagues now provide compelling data suggesting thymectomy may not be effective in MuSK-positive myasthenia gravis.”
The study’s follow-up is long enough for the findings to be clinically “relevant to all physicians treating myasthenia gravis,” said Robert W. Irwin, MD, Cochair of the AANEM Annual Meeting Program Committee.
Disability in Patients With Stiff Person Syndrome May Progress Faster Than Thought
A study emphasizes the importance of early treatment.
WASHINGTON, DC—Stiff person syndrome leads to disability if therapy is not initiated early in the disease course, according to a prospective study presented at the 2018 Annual Meeting of the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM). In addition, patients with stiff person syndrome may have “faster progression of disablement than originally reported and believed,” said lead study author Goran Rakocevic, MD. Dr. Rakocevic is Associate Professor of Neurology, Director of the Neuromuscular Electrodiagnostic Laboratory, Clinical Director of the Jefferson Weinberg ALS Center, and Director of the Neuromuscular Medicine Fellowship Program at Thomas Jefferson University in Philadelphia. 
Stiff person syndrome is a disorder characterized by muscle rigidity and episodic spasms in axial and limb musculature, as well as heightened sensitivity to external stimuli. To describe the natural history of stiff person syndrome, the extent of accumulated disability, and associated clinical features, Dr. Rakocevic and his research colleagues conducted a prospective cohort study in patients followed for up to eight years in a single center.
The cohort included 57 patients with mean age at disease onset of 42 (range, 22 to 60). Of these, 32 patients were examined every six months for two years without receiving immune therapies. The investigators assessed disease progression using quantitative scales of stiffness and heightened sensitivity.
Patients’ most frequent initial symptoms were leg stiffness, paraspinal muscle rigidity, and painful spasms. Although no patients required assistance for ambulation during the first two years of the disease, 46 patients (80%) lost the ability to walk independently during follow-up, despite symptomatic medications. In the longitudinal cohort, the number of stiff areas increased, which was consistent with worsening functional status and quality of life. The researchers confirmed a strong association between stiff person syndrome and the HLA-DR and DQ haplotypes.
The study is the largest prospective study of patients with stiff person syndrome and the first to provide longitudinal data on the natural course of the disorder in a large patient subgroup using objective clinical measures, Dr. Rakocevic and colleagues said. “The study shows that stiff person syndrome is a progressive autoimmune disease that leads to disability if ... immunotherapy is not applied,” said the investigators.
“Early diagnosis and management of stiff person syndrome can be challenging,” said A. Gordon Smith, MD, Cochair of the AANEM Annual Meeting Program Committee. The study by Dr. Rakocevic’s team demonstrates “that stiff person syndrome causes progressive stiffness and functional decline, with 80% [of patients] becoming unable to walk independently,” he said. “Their research emphasizes the need to treat early and will help clinicians recognize stiff person syndrome earlier in its course.”
The study adds to neurologists’ understanding of the rare disorder, and its strengths include the length of follow-up and the number of patients, said Robert W. Irwin, MD, Cochair of the AANEM Annual Meeting Program Committee.
A study emphasizes the importance of early treatment.
A study emphasizes the importance of early treatment.
WASHINGTON, DC—Stiff person syndrome leads to disability if therapy is not initiated early in the disease course, according to a prospective study presented at the 2018 Annual Meeting of the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM). In addition, patients with stiff person syndrome may have “faster progression of disablement than originally reported and believed,” said lead study author Goran Rakocevic, MD. Dr. Rakocevic is Associate Professor of Neurology, Director of the Neuromuscular Electrodiagnostic Laboratory, Clinical Director of the Jefferson Weinberg ALS Center, and Director of the Neuromuscular Medicine Fellowship Program at Thomas Jefferson University in Philadelphia.
Stiff person syndrome is a disorder characterized by muscle rigidity and episodic spasms in axial and limb musculature, as well as heightened sensitivity to external stimuli. To describe the natural history of stiff person syndrome, the extent of accumulated disability, and associated clinical features, Dr. Rakocevic and his research colleagues conducted a prospective cohort study in patients followed for up to eight years in a single center.
The cohort included 57 patients with mean age at disease onset of 42 (range, 22 to 60). Of these, 32 patients were examined every six months for two years without receiving immune therapies. The investigators assessed disease progression using quantitative scales of stiffness and heightened sensitivity.
Patients’ most frequent initial symptoms were leg stiffness, paraspinal muscle rigidity, and painful spasms. Although no patients required assistance for ambulation during the first two years of the disease, 46 patients (80%) lost the ability to walk independently during follow-up, despite symptomatic medications. In the longitudinal cohort, the number of stiff areas increased, which was consistent with worsening functional status and quality of life. The researchers confirmed a strong association between stiff person syndrome and the HLA-DR and DQ haplotypes.
The study is the largest prospective study of patients with stiff person syndrome and the first to provide longitudinal data on the natural course of the disorder in a large patient subgroup using objective clinical measures, Dr. Rakocevic and colleagues said. “The study shows that stiff person syndrome is a progressive autoimmune disease that leads to disability if ... immunotherapy is not applied,” said the investigators.
“Early diagnosis and management of stiff person syndrome can be challenging,” said A. Gordon Smith, MD, Cochair of the AANEM Annual Meeting Program Committee. The study by Dr. Rakocevic’s team demonstrates “that stiff person syndrome causes progressive stiffness and functional decline, with 80% [of patients] becoming unable to walk independently,” he said. “Their research emphasizes the need to treat early and will help clinicians recognize stiff person syndrome earlier in its course.”
The study adds to neurologists’ understanding of the rare disorder, and its strengths include the length of follow-up and the number of patients, said Robert W. Irwin, MD, Cochair of the AANEM Annual Meeting Program Committee.
WASHINGTON, DC—Stiff person syndrome leads to disability if therapy is not initiated early in the disease course, according to a prospective study presented at the 2018 Annual Meeting of the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM). In addition, patients with stiff person syndrome may have “faster progression of disablement than originally reported and believed,” said lead study author Goran Rakocevic, MD. Dr. Rakocevic is Associate Professor of Neurology, Director of the Neuromuscular Electrodiagnostic Laboratory, Clinical Director of the Jefferson Weinberg ALS Center, and Director of the Neuromuscular Medicine Fellowship Program at Thomas Jefferson University in Philadelphia.
Stiff person syndrome is a disorder characterized by muscle rigidity and episodic spasms in axial and limb musculature, as well as heightened sensitivity to external stimuli. To describe the natural history of stiff person syndrome, the extent of accumulated disability, and associated clinical features, Dr. Rakocevic and his research colleagues conducted a prospective cohort study in patients followed for up to eight years in a single center.
The cohort included 57 patients with mean age at disease onset of 42 (range, 22 to 60). Of these, 32 patients were examined every six months for two years without receiving immune therapies. The investigators assessed disease progression using quantitative scales of stiffness and heightened sensitivity.
Patients’ most frequent initial symptoms were leg stiffness, paraspinal muscle rigidity, and painful spasms. Although no patients required assistance for ambulation during the first two years of the disease, 46 patients (80%) lost the ability to walk independently during follow-up, despite symptomatic medications. In the longitudinal cohort, the number of stiff areas increased, which was consistent with worsening functional status and quality of life. The researchers confirmed a strong association between stiff person syndrome and the HLA-DR and DQ haplotypes.
The study is the largest prospective study of patients with stiff person syndrome and the first to provide longitudinal data on the natural course of the disorder in a large patient subgroup using objective clinical measures, Dr. Rakocevic and colleagues said. “The study shows that stiff person syndrome is a progressive autoimmune disease that leads to disability if ... immunotherapy is not applied,” said the investigators.
“Early diagnosis and management of stiff person syndrome can be challenging,” said A. Gordon Smith, MD, Cochair of the AANEM Annual Meeting Program Committee. The study by Dr. Rakocevic’s team demonstrates “that stiff person syndrome causes progressive stiffness and functional decline, with 80% [of patients] becoming unable to walk independently,” he said. “Their research emphasizes the need to treat early and will help clinicians recognize stiff person syndrome earlier in its course.”
The study adds to neurologists’ understanding of the rare disorder, and its strengths include the length of follow-up and the number of patients, said Robert W. Irwin, MD, Cochair of the AANEM Annual Meeting Program Committee.
New Registry Offers Insight Into Opsoclonus-Myoclonus Syndrome
WASHINGTON – a rare disease affecting only 1 in 5,000,000 individuals, mostly aged 1-5 years, based on data from a new patient registry.
In partnership with the National Organization of Rare Disorders (NORD) the nonprofit OMSLife Foundation has created a patient registry to better understand the disease experience in patients, wrote Mike Michaelis, chairman of OMSLife, and his colleagues. Early data from 275 enrolled patients were presented in a poster at the NORD Rare Summit, held by the National Organization for Rare Disorders.
The registry patients were mainly born in the United States (86%) and white (74%); approximately half were female. Of 150 patients who indicated symptoms at onset, 87% reported ataxia. Additional symptoms at onset were myoclonus (61%), opsoclonus (59%), tremors (46%), sleep disturbances (45%), temper tantrums (38%), vomiting (27%), fever (13%), headache (9%) and other symptoms (13%).
The researchers reviewed associations of symptoms at onset to determine the frequency of other symptoms for each individual symptom. Ataxia was present with 89% or higher instances of the other reported symptoms. Of note, some symptoms occurred more frequently than expected, such as temper tantrums and tremors in approximately 70% of patients with sleep disturbances. Myoclonus and opsoclonus, as well as fever and vomiting, also were significantly associated with the presence of other symptoms.
Two-thirds of the registry patients (69%) were diagnosed within 3 months of symptom onset, and 83% of these were diagnosed by a neurologist. Based on the Mitchell-Pike OMS severity scale, 59% of the patients met criteria for severe disease, 34% were classified as moderate, and 7% were mild. The registry is ongoing, but the current data provide insight on the clinical picture and common symptoms of OMS, the researchers said.
OMS Life was established in 2012 to support patients, caregivers, and researchers in raising awareness of opsoclonus-myoclonus syndrome as well as funds for research.
The study was supported by the OMSLife Foundation, NORD, and Trio Health Analytics. The researchers are employed by these organizations.
WASHINGTON – a rare disease affecting only 1 in 5,000,000 individuals, mostly aged 1-5 years, based on data from a new patient registry.
In partnership with the National Organization of Rare Disorders (NORD) the nonprofit OMSLife Foundation has created a patient registry to better understand the disease experience in patients, wrote Mike Michaelis, chairman of OMSLife, and his colleagues. Early data from 275 enrolled patients were presented in a poster at the NORD Rare Summit, held by the National Organization for Rare Disorders.
The registry patients were mainly born in the United States (86%) and white (74%); approximately half were female. Of 150 patients who indicated symptoms at onset, 87% reported ataxia. Additional symptoms at onset were myoclonus (61%), opsoclonus (59%), tremors (46%), sleep disturbances (45%), temper tantrums (38%), vomiting (27%), fever (13%), headache (9%) and other symptoms (13%).
The researchers reviewed associations of symptoms at onset to determine the frequency of other symptoms for each individual symptom. Ataxia was present with 89% or higher instances of the other reported symptoms. Of note, some symptoms occurred more frequently than expected, such as temper tantrums and tremors in approximately 70% of patients with sleep disturbances. Myoclonus and opsoclonus, as well as fever and vomiting, also were significantly associated with the presence of other symptoms.
Two-thirds of the registry patients (69%) were diagnosed within 3 months of symptom onset, and 83% of these were diagnosed by a neurologist. Based on the Mitchell-Pike OMS severity scale, 59% of the patients met criteria for severe disease, 34% were classified as moderate, and 7% were mild. The registry is ongoing, but the current data provide insight on the clinical picture and common symptoms of OMS, the researchers said.
OMS Life was established in 2012 to support patients, caregivers, and researchers in raising awareness of opsoclonus-myoclonus syndrome as well as funds for research.
The study was supported by the OMSLife Foundation, NORD, and Trio Health Analytics. The researchers are employed by these organizations.
WASHINGTON – a rare disease affecting only 1 in 5,000,000 individuals, mostly aged 1-5 years, based on data from a new patient registry.
In partnership with the National Organization of Rare Disorders (NORD) the nonprofit OMSLife Foundation has created a patient registry to better understand the disease experience in patients, wrote Mike Michaelis, chairman of OMSLife, and his colleagues. Early data from 275 enrolled patients were presented in a poster at the NORD Rare Summit, held by the National Organization for Rare Disorders.
The registry patients were mainly born in the United States (86%) and white (74%); approximately half were female. Of 150 patients who indicated symptoms at onset, 87% reported ataxia. Additional symptoms at onset were myoclonus (61%), opsoclonus (59%), tremors (46%), sleep disturbances (45%), temper tantrums (38%), vomiting (27%), fever (13%), headache (9%) and other symptoms (13%).
The researchers reviewed associations of symptoms at onset to determine the frequency of other symptoms for each individual symptom. Ataxia was present with 89% or higher instances of the other reported symptoms. Of note, some symptoms occurred more frequently than expected, such as temper tantrums and tremors in approximately 70% of patients with sleep disturbances. Myoclonus and opsoclonus, as well as fever and vomiting, also were significantly associated with the presence of other symptoms.
Two-thirds of the registry patients (69%) were diagnosed within 3 months of symptom onset, and 83% of these were diagnosed by a neurologist. Based on the Mitchell-Pike OMS severity scale, 59% of the patients met criteria for severe disease, 34% were classified as moderate, and 7% were mild. The registry is ongoing, but the current data provide insight on the clinical picture and common symptoms of OMS, the researchers said.
OMS Life was established in 2012 to support patients, caregivers, and researchers in raising awareness of opsoclonus-myoclonus syndrome as well as funds for research.
The study was supported by the OMSLife Foundation, NORD, and Trio Health Analytics. The researchers are employed by these organizations.
REPORTING FROM NORD SUMMIT 2018
Key clinical point: Most patients with OMS experienced multiple symptoms at disease onset; ataxia was the most common.
Major finding: Approximately 87% of patients with OMS reported ataxia at disease onset and 59% experienced severe disease.
Study details: The data come from a registry including 275 OMS patients.
Disclosures: The study was supported by the OMSLife Foundation, NORD, and Trio Health Analytics. The researchers are employed by these organizations.
Planning for ventilator-dependent patients during natural disasters
SAN ANTONIO – For patients with neuromuscular disorders, the stress and danger from natural disasters such Hurricane Harvey are best avoided by leaving the area as soon as possible, according to Venessa A. Holland, MD, FCCP, of Houston Methodist Hospital.
While none of Dr. Holland’s patients died during this catastrophic hurricane, there were considerable challenges, particularly for those trapped by the many trillion gallons of water fell on Texas and Louisiana in August 2017. Houston was flooded, and hospitals and other medical facilities were hit hard. The vulnerability of ventilator-dependent and incapacitated patients was of particular concern.
In one case, a ventilator-dependent patient trapped by flood waters at home became diaphoretic and hypotensive. The patient was treated with electrolyte-replacement sports drink administered via percutaneous endoscopic gastrostomy (PEG) tube, Dr. Holland told attendees at the annual meeting of the American College of Chest Physicians.
Dr. Holland spoke in a video interview about how neuromuscular disorder patients fared during Hurricane Harvey and her recommendations for the next natural disaster.
Dr. Holland disclosed that she previously served as a consultant to Hill-Rom.
SAN ANTONIO – For patients with neuromuscular disorders, the stress and danger from natural disasters such Hurricane Harvey are best avoided by leaving the area as soon as possible, according to Venessa A. Holland, MD, FCCP, of Houston Methodist Hospital.
While none of Dr. Holland’s patients died during this catastrophic hurricane, there were considerable challenges, particularly for those trapped by the many trillion gallons of water fell on Texas and Louisiana in August 2017. Houston was flooded, and hospitals and other medical facilities were hit hard. The vulnerability of ventilator-dependent and incapacitated patients was of particular concern.
In one case, a ventilator-dependent patient trapped by flood waters at home became diaphoretic and hypotensive. The patient was treated with electrolyte-replacement sports drink administered via percutaneous endoscopic gastrostomy (PEG) tube, Dr. Holland told attendees at the annual meeting of the American College of Chest Physicians.
Dr. Holland spoke in a video interview about how neuromuscular disorder patients fared during Hurricane Harvey and her recommendations for the next natural disaster.
Dr. Holland disclosed that she previously served as a consultant to Hill-Rom.
SAN ANTONIO – For patients with neuromuscular disorders, the stress and danger from natural disasters such Hurricane Harvey are best avoided by leaving the area as soon as possible, according to Venessa A. Holland, MD, FCCP, of Houston Methodist Hospital.
While none of Dr. Holland’s patients died during this catastrophic hurricane, there were considerable challenges, particularly for those trapped by the many trillion gallons of water fell on Texas and Louisiana in August 2017. Houston was flooded, and hospitals and other medical facilities were hit hard. The vulnerability of ventilator-dependent and incapacitated patients was of particular concern.
In one case, a ventilator-dependent patient trapped by flood waters at home became diaphoretic and hypotensive. The patient was treated with electrolyte-replacement sports drink administered via percutaneous endoscopic gastrostomy (PEG) tube, Dr. Holland told attendees at the annual meeting of the American College of Chest Physicians.
Dr. Holland spoke in a video interview about how neuromuscular disorder patients fared during Hurricane Harvey and her recommendations for the next natural disaster.
Dr. Holland disclosed that she previously served as a consultant to Hill-Rom.
REPORTING FROM CHEST 2018
Neurologic disease eventually affects half of women and one-third of men
Around one-half of women and one-third of men will develop dementia, stroke, or parkinsonism during their lifetime, based on results from the population-based Rotterdam study published in the Oct. 1 online edition of the Journal of Neurology, Neurosurgery & Psychiatry.
The study involved 12,102 individuals (57.7% women) who were aged 45 years or older and free from neurologic disease at baseline who were followed for 26 years.
Silvan Licher, MD, and colleagues from the University Medical Center Rotterdam (the Netherlands) found that a 45-year-old woman had a 48.2% overall remaining lifetime risk of developing dementia, stroke, or parkinsonism, while a 45-year-old man had a 36.3% lifetime risk.
“There are currently no disease-modifying drugs available for dementia and most causes of parkinsonism, and prevention of stroke is hampered by suboptimal adherence to effective preventive strategies or unmet guideline thresholds,” the authors wrote. “Yet, a delay in onset of these common neurologic diseases by merely a few years could reduce the population burden of these diseases substantially.”
Women aged 45 years had a significantly higher lifetime risk than men of developing dementia (31.4% vs. 18.6% respectively) and stroke (21.6% vs. 19.3%), but the risk of parkinsonism was similar between the sexes.
Women also had a significantly greater lifetime risk of developing more than one neurologic disease, compared with men (4% vs. 3.1%, P less than .001), largely because of the overlap between dementia and stroke.
At age 45 women had the greatest risk of dementia, but as men and women aged, their remaining lifetime risk of dementia increased relative to other neurologic diseases. After age 85 years, 66.6% of first diagnoses in women and 55.6% in men were dementia.
By comparison, first manifestation of stroke was the greatest threat to men aged 45. Men were also at a significantly higher risk for stroke at a younger age – before age 75 years – than were women (8.4% vs. 5.8%).
In the case of parkinsonism, the lifetime risk peaked earlier than it did for dementia and stroke, and was relatively low after the age of 85 years, with no significant differences in risk between men and women.
The authors also considered what effect a delay in disease onset and occurrence might have on remaining lifetime risk for neurologic disease. They found that a 1, 2, or 3-year delay in the onset of all neurologic disease was associated with a 20% reduction in lifetime risk in individuals aged 45 years or older, and a greater than 50% reduction in risk in the very oldest.
A 3-year delay in the onset of dementia reduced the lifetime risk by 15% for both men and women aged 45 years and granted a 30% reduction in risk to those aged 45 years or older.
The Rotterdam study is supported by Erasmus MC and Erasmus University Rotterdam, The Netherlands Organization for Scientific Research, The Netherlands Organization for Health Research and Development, the Research Institute for Diseases in the Elderly, The Netherlands Genomics Initiative, the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports, the European Commission and the Municipality of Rotterdam, the Netherlands Consortium for Healthy Ageing, and the Dutch Heart Foundation. No conflicts of interest were declared.
SOURCE: Licher S et al. JNNP. 2018 Oct 1. doi: 10.1136/jnnp-2018-318650.
Around one-half of women and one-third of men will develop dementia, stroke, or parkinsonism during their lifetime, based on results from the population-based Rotterdam study published in the Oct. 1 online edition of the Journal of Neurology, Neurosurgery & Psychiatry.
The study involved 12,102 individuals (57.7% women) who were aged 45 years or older and free from neurologic disease at baseline who were followed for 26 years.
Silvan Licher, MD, and colleagues from the University Medical Center Rotterdam (the Netherlands) found that a 45-year-old woman had a 48.2% overall remaining lifetime risk of developing dementia, stroke, or parkinsonism, while a 45-year-old man had a 36.3% lifetime risk.
“There are currently no disease-modifying drugs available for dementia and most causes of parkinsonism, and prevention of stroke is hampered by suboptimal adherence to effective preventive strategies or unmet guideline thresholds,” the authors wrote. “Yet, a delay in onset of these common neurologic diseases by merely a few years could reduce the population burden of these diseases substantially.”
Women aged 45 years had a significantly higher lifetime risk than men of developing dementia (31.4% vs. 18.6% respectively) and stroke (21.6% vs. 19.3%), but the risk of parkinsonism was similar between the sexes.
Women also had a significantly greater lifetime risk of developing more than one neurologic disease, compared with men (4% vs. 3.1%, P less than .001), largely because of the overlap between dementia and stroke.
At age 45 women had the greatest risk of dementia, but as men and women aged, their remaining lifetime risk of dementia increased relative to other neurologic diseases. After age 85 years, 66.6% of first diagnoses in women and 55.6% in men were dementia.
By comparison, first manifestation of stroke was the greatest threat to men aged 45. Men were also at a significantly higher risk for stroke at a younger age – before age 75 years – than were women (8.4% vs. 5.8%).
In the case of parkinsonism, the lifetime risk peaked earlier than it did for dementia and stroke, and was relatively low after the age of 85 years, with no significant differences in risk between men and women.
The authors also considered what effect a delay in disease onset and occurrence might have on remaining lifetime risk for neurologic disease. They found that a 1, 2, or 3-year delay in the onset of all neurologic disease was associated with a 20% reduction in lifetime risk in individuals aged 45 years or older, and a greater than 50% reduction in risk in the very oldest.
A 3-year delay in the onset of dementia reduced the lifetime risk by 15% for both men and women aged 45 years and granted a 30% reduction in risk to those aged 45 years or older.
The Rotterdam study is supported by Erasmus MC and Erasmus University Rotterdam, The Netherlands Organization for Scientific Research, The Netherlands Organization for Health Research and Development, the Research Institute for Diseases in the Elderly, The Netherlands Genomics Initiative, the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports, the European Commission and the Municipality of Rotterdam, the Netherlands Consortium for Healthy Ageing, and the Dutch Heart Foundation. No conflicts of interest were declared.
SOURCE: Licher S et al. JNNP. 2018 Oct 1. doi: 10.1136/jnnp-2018-318650.
Around one-half of women and one-third of men will develop dementia, stroke, or parkinsonism during their lifetime, based on results from the population-based Rotterdam study published in the Oct. 1 online edition of the Journal of Neurology, Neurosurgery & Psychiatry.
The study involved 12,102 individuals (57.7% women) who were aged 45 years or older and free from neurologic disease at baseline who were followed for 26 years.
Silvan Licher, MD, and colleagues from the University Medical Center Rotterdam (the Netherlands) found that a 45-year-old woman had a 48.2% overall remaining lifetime risk of developing dementia, stroke, or parkinsonism, while a 45-year-old man had a 36.3% lifetime risk.
“There are currently no disease-modifying drugs available for dementia and most causes of parkinsonism, and prevention of stroke is hampered by suboptimal adherence to effective preventive strategies or unmet guideline thresholds,” the authors wrote. “Yet, a delay in onset of these common neurologic diseases by merely a few years could reduce the population burden of these diseases substantially.”
Women aged 45 years had a significantly higher lifetime risk than men of developing dementia (31.4% vs. 18.6% respectively) and stroke (21.6% vs. 19.3%), but the risk of parkinsonism was similar between the sexes.
Women also had a significantly greater lifetime risk of developing more than one neurologic disease, compared with men (4% vs. 3.1%, P less than .001), largely because of the overlap between dementia and stroke.
At age 45 women had the greatest risk of dementia, but as men and women aged, their remaining lifetime risk of dementia increased relative to other neurologic diseases. After age 85 years, 66.6% of first diagnoses in women and 55.6% in men were dementia.
By comparison, first manifestation of stroke was the greatest threat to men aged 45. Men were also at a significantly higher risk for stroke at a younger age – before age 75 years – than were women (8.4% vs. 5.8%).
In the case of parkinsonism, the lifetime risk peaked earlier than it did for dementia and stroke, and was relatively low after the age of 85 years, with no significant differences in risk between men and women.
The authors also considered what effect a delay in disease onset and occurrence might have on remaining lifetime risk for neurologic disease. They found that a 1, 2, or 3-year delay in the onset of all neurologic disease was associated with a 20% reduction in lifetime risk in individuals aged 45 years or older, and a greater than 50% reduction in risk in the very oldest.
A 3-year delay in the onset of dementia reduced the lifetime risk by 15% for both men and women aged 45 years and granted a 30% reduction in risk to those aged 45 years or older.
The Rotterdam study is supported by Erasmus MC and Erasmus University Rotterdam, The Netherlands Organization for Scientific Research, The Netherlands Organization for Health Research and Development, the Research Institute for Diseases in the Elderly, The Netherlands Genomics Initiative, the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports, the European Commission and the Municipality of Rotterdam, the Netherlands Consortium for Healthy Ageing, and the Dutch Heart Foundation. No conflicts of interest were declared.
SOURCE: Licher S et al. JNNP. 2018 Oct 1. doi: 10.1136/jnnp-2018-318650.
FROM JOURNAL OF NEUROLOGY, NEUROSURGERY & PSYCHIATRY
Major finding: A 45-year-old woman has a 48.2% lifetime risk of stroke, dementia, or parkinsonism, while a man has a 36.3% lifetime risk.
Study details: Population-based cohort study in 12,102 individuals.
Disclosures: The Rotterdam study is supported by Erasmus MC and Erasmus University Rotterdam, The Netherlands Organization for Scientific Research, The Netherlands Organization for Health Research and Development, the Research Institute for Diseases in the Elderly, The Netherlands Genomics Initiative, the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports, the European Commission and the Municipality of Rotterdam, the Netherlands Consortium for Healthy Ageing, and the Dutch Heart Foundation. No financial conflicts of interest were declared.
Source: Licher S et al. JNNP. 2018 Oct 1. doi: 10.1136/jnnp-2018-318650.