Clinical Topics & News

To the Editor:

A 50-year old man with Fitzpatrick skin type IV, human immunodeficiency virus (HIV), fatty liver disease, and moderate psoriasis (10% body surface area [BSA] affected) currently treated with clobetasol spray and calcitriol ointment presented with persistent psoriatic lesions on the trunk, arms, legs, and buttocks. His CD4 count was 460 and his HIV RNA count was 48 copies/mL on polymerase chain reaction 2 months prior to the current presentation. He had been undergoing phototherapy 3 times weekly for the last 5 months for treatment of psoriasis.

At the current presentation, he was started on an apremilast starter pack with the dosage titrated from 10 mg to 30 mg over the course of 1 week. He was maintained on a dose of 30 mg twice daily after 1 week and continued clobetasol spray, calcitriol ointment, and phototherapy 3 times weekly with the intent to reduce the frequency after adequate control of psoriasis was achieved. After 3 months of treatment, the affected BSA was 0%. He continued apremilast, and phototherapy was reduced to once weekly. Phototherapy was discontinued after 7 months of concomitant treatment with apremilast after clearance was maintained. It was reinitiated twice weekly after a mild flare (3% BSA affected). After 20 total months of treatment, the patient was no longer able to afford apremilast treatment and presented with a severe psoriasis flare (40% BSA affected). He was switched to acitretin with a plan to apply for apremilast financial assistance programs.

Psoriasis treatment in the HIV population poses a challenge given the immunosuppressed state of these patients, the risk of reactivation of latent infections, and the refractory nature of psoriasis in the setting of HIV. Two of the authors (S.P.R. and J.J.W.) previously reported a case of moderate to severe psoriasis in a patient with HIV and hepatitis C who demonstrated treatment success with apremilast until it was discontinued due to financial implications.¹ Currently, apremilast is not widely used to treat psoriasis in the HIV population. The National Psoriasis Foundation 2010 guidelines recommended UV light therapy for treatment of moderate to severe psoriasis in HIV-positive patients, with oral retinoids as the second-line treatment.² There remains a need for updated guidelines on the use of systemic agents for psoriasis treatment in the HIV population.

Apremilast, a phosphodiesterase 4 inhibitor, is an oral therapy that restores the balance of proinflammatory and anti-inflammatory cytokines by inhibiting inflammatory cytokine (eg, tumor necrosis factor α, IFN-γ, IL-2, IL-12, IL-23) secretion and stimulating anti-inflammatory cytokine (eg, IL-6, IL-10) production. In 2015, the phase 3 ESTEEM 1³ and ESTEEM 2⁴ trials demonstrated the efficacy of apremilast 30 mg twice daily for treatment of psoriasis. In both trials, the psoriasis area and severity index 75 response rate at week 16 was significantly higher with apremilast compared to placebo alone (33.1% and 28.8% vs 5.2% and 5.8%, respectively; P<.001 for both trials). Apremilast also was noted to improve difficult-to-treat nail, scalp, and palmoplantar psoriasis.^3,4

Use of other systemic agents such as tumor necrosis factor α inhibitors and ustekinumab has been reported in HIV-positive patients.^5-7 There is no current data on IL-17 and IL-23 inhibitors. Acitretin generally is recommended as a second-line agent in HIV patients given its lack of immunosuppression²; however, methotrexate and cyclosporine should be avoided given the risk of opportunistic infections.⁸

Apremilast is a promising therapy with a favorable safety profile that should be considered as an adjuvant treatment to first-line agents such as phototherapy in HIV-positive patients. Apremilast has been successfully used in an HIV patient with a concomitant chronic hepatitis C infection.¹ Systemic medications such as apremilast should be managed in coordination with infectious disease specialists with close monitoring of CD4 levels and viral loads as well as prophylactic agents.

To the Editor:

A 50-year old man with Fitzpatrick skin type IV, human immunodeficiency virus (HIV), fatty liver disease, and moderate psoriasis (10% body surface area [BSA] affected) currently treated with clobetasol spray and calcitriol ointment presented with persistent psoriatic lesions on the trunk, arms, legs, and buttocks. His CD4 count was 460 and his HIV RNA count was 48 copies/mL on polymerase chain reaction 2 months prior to the current presentation. He had been undergoing phototherapy 3 times weekly for the last 5 months for treatment of psoriasis.

At the current presentation, he was started on an apremilast starter pack with the dosage titrated from 10 mg to 30 mg over the course of 1 week. He was maintained on a dose of 30 mg twice daily after 1 week and continued clobetasol spray, calcitriol ointment, and phototherapy 3 times weekly with the intent to reduce the frequency after adequate control of psoriasis was achieved. After 3 months of treatment, the affected BSA was 0%. He continued apremilast, and phototherapy was reduced to once weekly. Phototherapy was discontinued after 7 months of concomitant treatment with apremilast after clearance was maintained. It was reinitiated twice weekly after a mild flare (3% BSA affected). After 20 total months of treatment, the patient was no longer able to afford apremilast treatment and presented with a severe psoriasis flare (40% BSA affected). He was switched to acitretin with a plan to apply for apremilast financial assistance programs.

Psoriasis treatment in the HIV population poses a challenge given the immunosuppressed state of these patients, the risk of reactivation of latent infections, and the refractory nature of psoriasis in the setting of HIV. Two of the authors (S.P.R. and J.J.W.) previously reported a case of moderate to severe psoriasis in a patient with HIV and hepatitis C who demonstrated treatment success with apremilast until it was discontinued due to financial implications.¹ Currently, apremilast is not widely used to treat psoriasis in the HIV population. The National Psoriasis Foundation 2010 guidelines recommended UV light therapy for treatment of moderate to severe psoriasis in HIV-positive patients, with oral retinoids as the second-line treatment.² There remains a need for updated guidelines on the use of systemic agents for psoriasis treatment in the HIV population.

Apremilast, a phosphodiesterase 4 inhibitor, is an oral therapy that restores the balance of proinflammatory and anti-inflammatory cytokines by inhibiting inflammatory cytokine (eg, tumor necrosis factor α, IFN-γ, IL-2, IL-12, IL-23) secretion and stimulating anti-inflammatory cytokine (eg, IL-6, IL-10) production. In 2015, the phase 3 ESTEEM 1³ and ESTEEM 2⁴ trials demonstrated the efficacy of apremilast 30 mg twice daily for treatment of psoriasis. In both trials, the psoriasis area and severity index 75 response rate at week 16 was significantly higher with apremilast compared to placebo alone (33.1% and 28.8% vs 5.2% and 5.8%, respectively; P<.001 for both trials). Apremilast also was noted to improve difficult-to-treat nail, scalp, and palmoplantar psoriasis.^3,4

Use of other systemic agents such as tumor necrosis factor α inhibitors and ustekinumab has been reported in HIV-positive patients.^5-7 There is no current data on IL-17 and IL-23 inhibitors. Acitretin generally is recommended as a second-line agent in HIV patients given its lack of immunosuppression²; however, methotrexate and cyclosporine should be avoided given the risk of opportunistic infections.⁸

Apremilast is a promising therapy with a favorable safety profile that should be considered as an adjuvant treatment to first-line agents such as phototherapy in HIV-positive patients. Apremilast has been successfully used in an HIV patient with a concomitant chronic hepatitis C infection.¹ Systemic medications such as apremilast should be managed in coordination with infectious disease specialists with close monitoring of CD4 levels and viral loads as well as prophylactic agents.

To the Editor:

A 50-year old man with Fitzpatrick skin type IV, human immunodeficiency virus (HIV), fatty liver disease, and moderate psoriasis (10% body surface area [BSA] affected) currently treated with clobetasol spray and calcitriol ointment presented with persistent psoriatic lesions on the trunk, arms, legs, and buttocks. His CD4 count was 460 and his HIV RNA count was 48 copies/mL on polymerase chain reaction 2 months prior to the current presentation. He had been undergoing phototherapy 3 times weekly for the last 5 months for treatment of psoriasis.

At the current presentation, he was started on an apremilast starter pack with the dosage titrated from 10 mg to 30 mg over the course of 1 week. He was maintained on a dose of 30 mg twice daily after 1 week and continued clobetasol spray, calcitriol ointment, and phototherapy 3 times weekly with the intent to reduce the frequency after adequate control of psoriasis was achieved. After 3 months of treatment, the affected BSA was 0%. He continued apremilast, and phototherapy was reduced to once weekly. Phototherapy was discontinued after 7 months of concomitant treatment with apremilast after clearance was maintained. It was reinitiated twice weekly after a mild flare (3% BSA affected). After 20 total months of treatment, the patient was no longer able to afford apremilast treatment and presented with a severe psoriasis flare (40% BSA affected). He was switched to acitretin with a plan to apply for apremilast financial assistance programs.

Psoriasis treatment in the HIV population poses a challenge given the immunosuppressed state of these patients, the risk of reactivation of latent infections, and the refractory nature of psoriasis in the setting of HIV. Two of the authors (S.P.R. and J.J.W.) previously reported a case of moderate to severe psoriasis in a patient with HIV and hepatitis C who demonstrated treatment success with apremilast until it was discontinued due to financial implications.¹ Currently, apremilast is not widely used to treat psoriasis in the HIV population. The National Psoriasis Foundation 2010 guidelines recommended UV light therapy for treatment of moderate to severe psoriasis in HIV-positive patients, with oral retinoids as the second-line treatment.² There remains a need for updated guidelines on the use of systemic agents for psoriasis treatment in the HIV population.

Apremilast, a phosphodiesterase 4 inhibitor, is an oral therapy that restores the balance of proinflammatory and anti-inflammatory cytokines by inhibiting inflammatory cytokine (eg, tumor necrosis factor α, IFN-γ, IL-2, IL-12, IL-23) secretion and stimulating anti-inflammatory cytokine (eg, IL-6, IL-10) production. In 2015, the phase 3 ESTEEM 1³ and ESTEEM 2⁴ trials demonstrated the efficacy of apremilast 30 mg twice daily for treatment of psoriasis. In both trials, the psoriasis area and severity index 75 response rate at week 16 was significantly higher with apremilast compared to placebo alone (33.1% and 28.8% vs 5.2% and 5.8%, respectively; P<.001 for both trials). Apremilast also was noted to improve difficult-to-treat nail, scalp, and palmoplantar psoriasis.^3,4

Use of other systemic agents such as tumor necrosis factor α inhibitors and ustekinumab has been reported in HIV-positive patients.^5-7 There is no current data on IL-17 and IL-23 inhibitors. Acitretin generally is recommended as a second-line agent in HIV patients given its lack of immunosuppression²; however, methotrexate and cyclosporine should be avoided given the risk of opportunistic infections.⁸

Apremilast is a promising therapy with a favorable safety profile that should be considered as an adjuvant treatment to first-line agents such as phototherapy in HIV-positive patients. Apremilast has been successfully used in an HIV patient with a concomitant chronic hepatitis C infection.¹ Systemic medications such as apremilast should be managed in coordination with infectious disease specialists with close monitoring of CD4 levels and viral loads as well as prophylactic agents.

Dr. Rapoport: Do you commonly see patients who present with symptoms of both central and peripheral symptoms in practice?

Dr. Romero-Reyes: Yes, I see patients that present with temporomandibular disorders (TMD) and headache comorbidity, as well as patients with migraine, tension-type headache, and cervicogenic headache with myofascial pain.

Dr. Rapoport: Why do you think this condition is so challenging to treat?

Dr. Romero-Reyes: I think this is because of the lack of understanding and awareness that in addition to the multifactorial nature of headache disorders, other types of disorders that are not neurovascular in origin may influence trigeminovascular nociception, and these types of non-neurovascular disorders involve the skill and knowledge of other expertise.

Headaches receiving inputs from extracranial structures such as in TMD (temporomandibular joint [TMJ] and muscles of mastication) and/or cervical structures (cervical spine, cervical muscles) require multidisciplinary evaluation and management. In these cases, the management should involve a neurologist specialized in headache disorders, a dentist trained in TMD and orofacial pain disorders, and a physical therapist with special training in craniofacial and cervical Therapeutics. Multidisciplinary communication is key for successful management.

Another reason is that myofascial pain (MFP) is often overlooked in patients with headache disorders. In my experience, patients with episodic and chronic migraine, episodic and chronic tension-type headache, cervicogenic headache, and patients presenting TMD and headache comorbidity can present trigger points in the craniofacial and cervical muscles, an indication of MFP. It has been reported that these patients present a higher disability impact. The presence of MFP may be contributing to the activation of the trigeminovascular system and therefore facilitate, exacerbate, and perpetuate headache symptomatology and may accelerate the progression to a more chronic form of the disorder.

Dr. Rapoport: In your opinion, is this considered a controversial topic? Why or why not?
 

Dr. Romero-Reyes: Yes, I think it is necessary to clarify that tenderness in the back of the head or of neck muscles present in headache patients does not necessarily imply that it is due to a nerve compression. This could also be caused by local myalgia but more commonly, from latent or active myofascial trigger points present in the muscles of the area being palpated, or by referred pain beyond the area of the muscle being palpated. Suboccipital muscles (in the occiput area) are not the only muscle group that is associated with headache and neck pain symptomatology. For example, the trapezius muscle, which is an overlooked source of tension- type and cervicogenic headache, can present trigger points that can refer pain to the shoulder, neck, head, face and the eye. In addition, other craniofacial and cervical muscles such as the sternocleidomastoid (SCM) and temporalis muscles have been shown to be associated with headache symptomatology in the migraineur, as well as the chronic tension-type headache patient. Other muscles that also refer to the craniofacial area and can elicit headache and neck pain symptomatology include the masseter, occipitofrontalis, splenius capitis, splenius cervicis, semispinalis capitis, semispinalis cervicis and multifidi (cervical). The presence of trigger points in these muscles do not support or warrant the need to be removed or managed with non-conservative approaches.

Myofascial trigger points can result from muscle injury and overload, parafunctional activity, and poor head and neck posture. MFP is characterized by a regional pain and presence of localized tender areas (trigger points) in muscle, fascia or tendons that reproduce pain when palpated, and produce a pattern of regional pain spreading along the muscle palpated, or beyond the location boundary of the muscle palpated. It has been shown by microdyalisis that inflammatory mediators and neuropeptides are present in the area of an active trigger point. In addition, an increase of electromyography activity has been shown in trigger points in patients with chronic tension-type headache when compared with controls.

The importance of an evaluation by a skilled clinician in the craniofacial and cervical area to verify the source of pain is critical.  The patient may be reporting pain in one area, but the source of the pain is in another area, and this is typical symptomatology present when there are active trigger points. In addition, an assessment of any contributing factors arising from the cervical spine (eg, poor posture) and craniofacial area (eg, TMD) that may exacerbate headache symptomatology is vital to proper diagnosis.

In my experience, patients with migraine, tension-type headache, cervicogenic headache, and TMD and headache comorbidity present MFP perpetuating headache symptomatology. MFP is not managed by surgical interventions. This perpetuating factor can be managed effectively with conservative measures. The plan is tailored for each patient’s needs. In general, the plan of management may include trigger point injections in the muscle with anesthetics, dry needling, and a physical therapy plan that may include education regarding habits and posture, exercises and physical therapy modalities, which are crucial to relieve pain and increase function. In cases of TMD and headache comorbidity, an occlusal appliance (stabilization appliance) can be included if necessary. We should also consider behavioral therapies (especially EMG biofeedback training) and some oral anti-inflammatories or muscle relaxants in the beginning of management, together with the plan of management mentioned above.

With these approaches to manage the MFP component in headache patients, I have been able to see that in migraineurs with MFP, the frequency and severity of the attacks decrease significantly. The patient may still experience migraine attacks, but feel happy to have the possibility to reduce medication intake and be in more control of their pain. In patients with tension-type headache, I have seen this even more dramatically.

This is telling us that headache pathophysiology involves a “conversation” between the peripheral and central nervous system, which influence each other. Peripheral nociceptive input coming from extracranial structures can induce trigeminovascular activation and therefore exacerbate a headache disorder and vice versa.  Chronic myofascial pain may be the result of central sensitization due to the protracted peripheral nociceptive input (eg, poor posture, neck strain, parafunctional activity), therefore perpetuating the headache disorder even more.

Dr. Rapoport: Do you have any other comments about the article Treatment Challenges When Headache Has Central and Peripheral Involvement that you would like to share with our readers?

Dr. Romero-Reyes: It is simplistic to say migraine is either a peripheral or a central disorder, or that symptoms are either peripheral or central. Beyond thinking about migraine pain, migraine is fundamentally a brain (central) disorder. Its associated symptoms (nausea, phonophobia, photophobia) tell us this. Migraine headache is complex, and most likely the result of central mechanisms that can be influenced by peripheral inputs from the craniofacial and cervical region.

Embarking on surgical interventions for the management of headache disorders warrants a caution since it is still an experimental research question and the need of such therapies should be evaluated against conservative management. We are in a very exciting and hopeful time for migraine management. New evidence-based options from biological agents, such as anti-calcitonin gene-related peptide (CGRP) therapies, to non-pharmacological approaches, such as neuromodulation, can be offered to the patients. If the patient is experiencing pain in the neck area or other craniofacial area, it is recommended to have a thorough evaluation by a physical therapist with special training in cervical and craniofacial therapeutics and/or a dentist trained in TMD and orofacial pain disorders to work in consultation with a neurologist to elaborate a personalized management plan. Do not overlook the contribution of myofascial pain (trigger points) as well as TMD in the symptomatology of headache disorders. Few patients need to undergo surgical measures of peripheral nerves and muscles for improvement. An exhaustive evaluation must be undertaken first.

Resources for patients:

AHS

https://americanheadachesociety.org/

https://americanheadachesociety.org/wp-content/uploads/2018/06/Choosing-Wisely-Flyer.pdf

AAOP

https://aaop.clubexpress.com/content.aspx?sl=1152088466

PTBCTT

https://ptbcct.org/

Dr. Rapoport: Do you commonly see patients who present with symptoms of both central and peripheral symptoms in practice?

Dr. Romero-Reyes: Yes, I see patients that present with temporomandibular disorders (TMD) and headache comorbidity, as well as patients with migraine, tension-type headache, and cervicogenic headache with myofascial pain.

Dr. Rapoport: Why do you think this condition is so challenging to treat?

Dr. Romero-Reyes: I think this is because of the lack of understanding and awareness that in addition to the multifactorial nature of headache disorders, other types of disorders that are not neurovascular in origin may influence trigeminovascular nociception, and these types of non-neurovascular disorders involve the skill and knowledge of other expertise.

Headaches receiving inputs from extracranial structures such as in TMD (temporomandibular joint [TMJ] and muscles of mastication) and/or cervical structures (cervical spine, cervical muscles) require multidisciplinary evaluation and management. In these cases, the management should involve a neurologist specialized in headache disorders, a dentist trained in TMD and orofacial pain disorders, and a physical therapist with special training in craniofacial and cervical Therapeutics. Multidisciplinary communication is key for successful management.

Another reason is that myofascial pain (MFP) is often overlooked in patients with headache disorders. In my experience, patients with episodic and chronic migraine, episodic and chronic tension-type headache, cervicogenic headache, and patients presenting TMD and headache comorbidity can present trigger points in the craniofacial and cervical muscles, an indication of MFP. It has been reported that these patients present a higher disability impact. The presence of MFP may be contributing to the activation of the trigeminovascular system and therefore facilitate, exacerbate, and perpetuate headache symptomatology and may accelerate the progression to a more chronic form of the disorder.

Dr. Rapoport: In your opinion, is this considered a controversial topic? Why or why not?
 

Dr. Romero-Reyes: Yes, I think it is necessary to clarify that tenderness in the back of the head or of neck muscles present in headache patients does not necessarily imply that it is due to a nerve compression. This could also be caused by local myalgia but more commonly, from latent or active myofascial trigger points present in the muscles of the area being palpated, or by referred pain beyond the area of the muscle being palpated. Suboccipital muscles (in the occiput area) are not the only muscle group that is associated with headache and neck pain symptomatology. For example, the trapezius muscle, which is an overlooked source of tension- type and cervicogenic headache, can present trigger points that can refer pain to the shoulder, neck, head, face and the eye. In addition, other craniofacial and cervical muscles such as the sternocleidomastoid (SCM) and temporalis muscles have been shown to be associated with headache symptomatology in the migraineur, as well as the chronic tension-type headache patient. Other muscles that also refer to the craniofacial area and can elicit headache and neck pain symptomatology include the masseter, occipitofrontalis, splenius capitis, splenius cervicis, semispinalis capitis, semispinalis cervicis and multifidi (cervical). The presence of trigger points in these muscles do not support or warrant the need to be removed or managed with non-conservative approaches.

Myofascial trigger points can result from muscle injury and overload, parafunctional activity, and poor head and neck posture. MFP is characterized by a regional pain and presence of localized tender areas (trigger points) in muscle, fascia or tendons that reproduce pain when palpated, and produce a pattern of regional pain spreading along the muscle palpated, or beyond the location boundary of the muscle palpated. It has been shown by microdyalisis that inflammatory mediators and neuropeptides are present in the area of an active trigger point. In addition, an increase of electromyography activity has been shown in trigger points in patients with chronic tension-type headache when compared with controls.

The importance of an evaluation by a skilled clinician in the craniofacial and cervical area to verify the source of pain is critical.  The patient may be reporting pain in one area, but the source of the pain is in another area, and this is typical symptomatology present when there are active trigger points. In addition, an assessment of any contributing factors arising from the cervical spine (eg, poor posture) and craniofacial area (eg, TMD) that may exacerbate headache symptomatology is vital to proper diagnosis.

In my experience, patients with migraine, tension-type headache, cervicogenic headache, and TMD and headache comorbidity present MFP perpetuating headache symptomatology. MFP is not managed by surgical interventions. This perpetuating factor can be managed effectively with conservative measures. The plan is tailored for each patient’s needs. In general, the plan of management may include trigger point injections in the muscle with anesthetics, dry needling, and a physical therapy plan that may include education regarding habits and posture, exercises and physical therapy modalities, which are crucial to relieve pain and increase function. In cases of TMD and headache comorbidity, an occlusal appliance (stabilization appliance) can be included if necessary. We should also consider behavioral therapies (especially EMG biofeedback training) and some oral anti-inflammatories or muscle relaxants in the beginning of management, together with the plan of management mentioned above.

With these approaches to manage the MFP component in headache patients, I have been able to see that in migraineurs with MFP, the frequency and severity of the attacks decrease significantly. The patient may still experience migraine attacks, but feel happy to have the possibility to reduce medication intake and be in more control of their pain. In patients with tension-type headache, I have seen this even more dramatically.

This is telling us that headache pathophysiology involves a “conversation” between the peripheral and central nervous system, which influence each other. Peripheral nociceptive input coming from extracranial structures can induce trigeminovascular activation and therefore exacerbate a headache disorder and vice versa.  Chronic myofascial pain may be the result of central sensitization due to the protracted peripheral nociceptive input (eg, poor posture, neck strain, parafunctional activity), therefore perpetuating the headache disorder even more.

Dr. Rapoport: Do you have any other comments about the article Treatment Challenges When Headache Has Central and Peripheral Involvement that you would like to share with our readers?

Dr. Romero-Reyes: It is simplistic to say migraine is either a peripheral or a central disorder, or that symptoms are either peripheral or central. Beyond thinking about migraine pain, migraine is fundamentally a brain (central) disorder. Its associated symptoms (nausea, phonophobia, photophobia) tell us this. Migraine headache is complex, and most likely the result of central mechanisms that can be influenced by peripheral inputs from the craniofacial and cervical region.

Embarking on surgical interventions for the management of headache disorders warrants a caution since it is still an experimental research question and the need of such therapies should be evaluated against conservative management. We are in a very exciting and hopeful time for migraine management. New evidence-based options from biological agents, such as anti-calcitonin gene-related peptide (CGRP) therapies, to non-pharmacological approaches, such as neuromodulation, can be offered to the patients. If the patient is experiencing pain in the neck area or other craniofacial area, it is recommended to have a thorough evaluation by a physical therapist with special training in cervical and craniofacial therapeutics and/or a dentist trained in TMD and orofacial pain disorders to work in consultation with a neurologist to elaborate a personalized management plan. Do not overlook the contribution of myofascial pain (trigger points) as well as TMD in the symptomatology of headache disorders. Few patients need to undergo surgical measures of peripheral nerves and muscles for improvement. An exhaustive evaluation must be undertaken first.

Resources for patients:

AHS

https://americanheadachesociety.org/

https://americanheadachesociety.org/wp-content/uploads/2018/06/Choosing-Wisely-Flyer.pdf

AAOP

https://aaop.clubexpress.com/content.aspx?sl=1152088466

PTBCTT

https://ptbcct.org/

Dr. Rapoport: Do you commonly see patients who present with symptoms of both central and peripheral symptoms in practice?

Dr. Romero-Reyes: Yes, I see patients that present with temporomandibular disorders (TMD) and headache comorbidity, as well as patients with migraine, tension-type headache, and cervicogenic headache with myofascial pain.

Dr. Rapoport: Why do you think this condition is so challenging to treat?

Dr. Romero-Reyes: I think this is because of the lack of understanding and awareness that in addition to the multifactorial nature of headache disorders, other types of disorders that are not neurovascular in origin may influence trigeminovascular nociception, and these types of non-neurovascular disorders involve the skill and knowledge of other expertise.

Headaches receiving inputs from extracranial structures such as in TMD (temporomandibular joint [TMJ] and muscles of mastication) and/or cervical structures (cervical spine, cervical muscles) require multidisciplinary evaluation and management. In these cases, the management should involve a neurologist specialized in headache disorders, a dentist trained in TMD and orofacial pain disorders, and a physical therapist with special training in craniofacial and cervical Therapeutics. Multidisciplinary communication is key for successful management.

Another reason is that myofascial pain (MFP) is often overlooked in patients with headache disorders. In my experience, patients with episodic and chronic migraine, episodic and chronic tension-type headache, cervicogenic headache, and patients presenting TMD and headache comorbidity can present trigger points in the craniofacial and cervical muscles, an indication of MFP. It has been reported that these patients present a higher disability impact. The presence of MFP may be contributing to the activation of the trigeminovascular system and therefore facilitate, exacerbate, and perpetuate headache symptomatology and may accelerate the progression to a more chronic form of the disorder.

Dr. Rapoport: In your opinion, is this considered a controversial topic? Why or why not?
 

Dr. Romero-Reyes: Yes, I think it is necessary to clarify that tenderness in the back of the head or of neck muscles present in headache patients does not necessarily imply that it is due to a nerve compression. This could also be caused by local myalgia but more commonly, from latent or active myofascial trigger points present in the muscles of the area being palpated, or by referred pain beyond the area of the muscle being palpated. Suboccipital muscles (in the occiput area) are not the only muscle group that is associated with headache and neck pain symptomatology. For example, the trapezius muscle, which is an overlooked source of tension- type and cervicogenic headache, can present trigger points that can refer pain to the shoulder, neck, head, face and the eye. In addition, other craniofacial and cervical muscles such as the sternocleidomastoid (SCM) and temporalis muscles have been shown to be associated with headache symptomatology in the migraineur, as well as the chronic tension-type headache patient. Other muscles that also refer to the craniofacial area and can elicit headache and neck pain symptomatology include the masseter, occipitofrontalis, splenius capitis, splenius cervicis, semispinalis capitis, semispinalis cervicis and multifidi (cervical). The presence of trigger points in these muscles do not support or warrant the need to be removed or managed with non-conservative approaches.

Myofascial trigger points can result from muscle injury and overload, parafunctional activity, and poor head and neck posture. MFP is characterized by a regional pain and presence of localized tender areas (trigger points) in muscle, fascia or tendons that reproduce pain when palpated, and produce a pattern of regional pain spreading along the muscle palpated, or beyond the location boundary of the muscle palpated. It has been shown by microdyalisis that inflammatory mediators and neuropeptides are present in the area of an active trigger point. In addition, an increase of electromyography activity has been shown in trigger points in patients with chronic tension-type headache when compared with controls.

The importance of an evaluation by a skilled clinician in the craniofacial and cervical area to verify the source of pain is critical.  The patient may be reporting pain in one area, but the source of the pain is in another area, and this is typical symptomatology present when there are active trigger points. In addition, an assessment of any contributing factors arising from the cervical spine (eg, poor posture) and craniofacial area (eg, TMD) that may exacerbate headache symptomatology is vital to proper diagnosis.

In my experience, patients with migraine, tension-type headache, cervicogenic headache, and TMD and headache comorbidity present MFP perpetuating headache symptomatology. MFP is not managed by surgical interventions. This perpetuating factor can be managed effectively with conservative measures. The plan is tailored for each patient’s needs. In general, the plan of management may include trigger point injections in the muscle with anesthetics, dry needling, and a physical therapy plan that may include education regarding habits and posture, exercises and physical therapy modalities, which are crucial to relieve pain and increase function. In cases of TMD and headache comorbidity, an occlusal appliance (stabilization appliance) can be included if necessary. We should also consider behavioral therapies (especially EMG biofeedback training) and some oral anti-inflammatories or muscle relaxants in the beginning of management, together with the plan of management mentioned above.

With these approaches to manage the MFP component in headache patients, I have been able to see that in migraineurs with MFP, the frequency and severity of the attacks decrease significantly. The patient may still experience migraine attacks, but feel happy to have the possibility to reduce medication intake and be in more control of their pain. In patients with tension-type headache, I have seen this even more dramatically.

This is telling us that headache pathophysiology involves a “conversation” between the peripheral and central nervous system, which influence each other. Peripheral nociceptive input coming from extracranial structures can induce trigeminovascular activation and therefore exacerbate a headache disorder and vice versa.  Chronic myofascial pain may be the result of central sensitization due to the protracted peripheral nociceptive input (eg, poor posture, neck strain, parafunctional activity), therefore perpetuating the headache disorder even more.

Dr. Rapoport: Do you have any other comments about the article Treatment Challenges When Headache Has Central and Peripheral Involvement that you would like to share with our readers?

Dr. Romero-Reyes: It is simplistic to say migraine is either a peripheral or a central disorder, or that symptoms are either peripheral or central. Beyond thinking about migraine pain, migraine is fundamentally a brain (central) disorder. Its associated symptoms (nausea, phonophobia, photophobia) tell us this. Migraine headache is complex, and most likely the result of central mechanisms that can be influenced by peripheral inputs from the craniofacial and cervical region.

Embarking on surgical interventions for the management of headache disorders warrants a caution since it is still an experimental research question and the need of such therapies should be evaluated against conservative management. We are in a very exciting and hopeful time for migraine management. New evidence-based options from biological agents, such as anti-calcitonin gene-related peptide (CGRP) therapies, to non-pharmacological approaches, such as neuromodulation, can be offered to the patients. If the patient is experiencing pain in the neck area or other craniofacial area, it is recommended to have a thorough evaluation by a physical therapist with special training in cervical and craniofacial therapeutics and/or a dentist trained in TMD and orofacial pain disorders to work in consultation with a neurologist to elaborate a personalized management plan. Do not overlook the contribution of myofascial pain (trigger points) as well as TMD in the symptomatology of headache disorders. Few patients need to undergo surgical measures of peripheral nerves and muscles for improvement. An exhaustive evaluation must be undertaken first.

Resources for patients:

AHS

https://americanheadachesociety.org/

https://americanheadachesociety.org/wp-content/uploads/2018/06/Choosing-Wisely-Flyer.pdf

AAOP

https://aaop.clubexpress.com/content.aspx?sl=1152088466

PTBCTT

https://ptbcct.org/

The Food and Drug Administration has approved cladribine (Mavenclad) tablets to treat adult patients with relapsing forms of multiple sclerosis (MS), including relapsing/remitting and active secondary progressive disease.

The drug’s manufacturer, EMD Serono, said in a press release that cladribine is the first short-course oral therapy for such patients, and its use is generally recommended for patients who have had an inadequate response to, or are unable to tolerate, an alternate drug indicated for the treatment of MS. Cladribine is not recommended for use in patients with clinically isolated syndrome.

The agency’s decision is based on results from a clinical trial of 1,326 patients with relapsing MS who had experienced at least one relapse in the previous 12 months. Patients who received cladribine had significantly fewer relapses than did those who received placebo; the progression of disability was also significantly reduced in the cladribine group, compared with placebo, according to the FDA’s announcement.

The most common adverse events associated with cladribine include upper respiratory tract infections, headache, and decreased lymphocyte counts. In addition, the medication must be dispensed with a patient medication guide because the label includes a boxed warning for increased risk of malignancy and fetal harm. Other warnings include a risk for decreased lymphocyte count, hematologic toxicity and bone marrow suppression, and graft-versus-host-disease.

“We are committed to supporting the development of safe and effective treatments for patients with multiple sclerosis. The approval of Mavenclad represents an additional option for patients who have tried another treatment without success,” Billy Dunn, MD, director of the division of neurology products in the FDA’s Center for Drug Evaluation and Research, said in the announcement.

The approved dose of cladribine is 3.5 mg/kg body weight over 2 years, administered as one treatment course of 1.75 mg/kg per year, each consisting of 2 treatment weeks. Additional courses of cladribine are not to be administered because retreatment with cladribine during years 3 and 4 may further increase the risk of malignancy. The safety and efficacy of reinitiating cladribine more than 2 years after completing two treatment courses has not been studied, according to EMD Serono.

Cladribine is approved in more than 50 other countries and was approved for use in the European Union in August 2017.

[email protected]

The Food and Drug Administration has approved cladribine (Mavenclad) tablets to treat adult patients with relapsing forms of multiple sclerosis (MS), including relapsing/remitting and active secondary progressive disease.

The drug’s manufacturer, EMD Serono, said in a press release that cladribine is the first short-course oral therapy for such patients, and its use is generally recommended for patients who have had an inadequate response to, or are unable to tolerate, an alternate drug indicated for the treatment of MS. Cladribine is not recommended for use in patients with clinically isolated syndrome.

The agency’s decision is based on results from a clinical trial of 1,326 patients with relapsing MS who had experienced at least one relapse in the previous 12 months. Patients who received cladribine had significantly fewer relapses than did those who received placebo; the progression of disability was also significantly reduced in the cladribine group, compared with placebo, according to the FDA’s announcement.

The most common adverse events associated with cladribine include upper respiratory tract infections, headache, and decreased lymphocyte counts. In addition, the medication must be dispensed with a patient medication guide because the label includes a boxed warning for increased risk of malignancy and fetal harm. Other warnings include a risk for decreased lymphocyte count, hematologic toxicity and bone marrow suppression, and graft-versus-host-disease.

“We are committed to supporting the development of safe and effective treatments for patients with multiple sclerosis. The approval of Mavenclad represents an additional option for patients who have tried another treatment without success,” Billy Dunn, MD, director of the division of neurology products in the FDA’s Center for Drug Evaluation and Research, said in the announcement.

The approved dose of cladribine is 3.5 mg/kg body weight over 2 years, administered as one treatment course of 1.75 mg/kg per year, each consisting of 2 treatment weeks. Additional courses of cladribine are not to be administered because retreatment with cladribine during years 3 and 4 may further increase the risk of malignancy. The safety and efficacy of reinitiating cladribine more than 2 years after completing two treatment courses has not been studied, according to EMD Serono.

Cladribine is approved in more than 50 other countries and was approved for use in the European Union in August 2017.

[email protected]

The Food and Drug Administration has approved cladribine (Mavenclad) tablets to treat adult patients with relapsing forms of multiple sclerosis (MS), including relapsing/remitting and active secondary progressive disease.

The drug’s manufacturer, EMD Serono, said in a press release that cladribine is the first short-course oral therapy for such patients, and its use is generally recommended for patients who have had an inadequate response to, or are unable to tolerate, an alternate drug indicated for the treatment of MS. Cladribine is not recommended for use in patients with clinically isolated syndrome.

The agency’s decision is based on results from a clinical trial of 1,326 patients with relapsing MS who had experienced at least one relapse in the previous 12 months. Patients who received cladribine had significantly fewer relapses than did those who received placebo; the progression of disability was also significantly reduced in the cladribine group, compared with placebo, according to the FDA’s announcement.

The most common adverse events associated with cladribine include upper respiratory tract infections, headache, and decreased lymphocyte counts. In addition, the medication must be dispensed with a patient medication guide because the label includes a boxed warning for increased risk of malignancy and fetal harm. Other warnings include a risk for decreased lymphocyte count, hematologic toxicity and bone marrow suppression, and graft-versus-host-disease.

“We are committed to supporting the development of safe and effective treatments for patients with multiple sclerosis. The approval of Mavenclad represents an additional option for patients who have tried another treatment without success,” Billy Dunn, MD, director of the division of neurology products in the FDA’s Center for Drug Evaluation and Research, said in the announcement.

The approved dose of cladribine is 3.5 mg/kg body weight over 2 years, administered as one treatment course of 1.75 mg/kg per year, each consisting of 2 treatment weeks. Additional courses of cladribine are not to be administered because retreatment with cladribine during years 3 and 4 may further increase the risk of malignancy. The safety and efficacy of reinitiating cladribine more than 2 years after completing two treatment courses has not been studied, according to EMD Serono.

Cladribine is approved in more than 50 other countries and was approved for use in the European Union in August 2017.

[email protected]

Discontinuing

How would you characterize the prevalence of MS in the elderly?

DR. CORBOY:  A recent large demographic study put together by the National MS Society found that there’s almost a million individuals diagnosed with MS over the course of the last 40 to 50 years. The largest population segment was those aged 55 to 64 years. People with MS aged 55 or older constituted 46% of all those with MS.

What disease-modifying therapies (DMTs) are approved by the FDA for the elderly?

DR. CORBOY: Of the drugs that have received FDA approval, most are for individuals over the age of 18 and there’s no specific age cutoff. However, there’s no data supporting DMT use in people over the age of 55 because they were excluded from the studies.

There’s one DMT, fingolimod, that was approved for use in patients under the age of 18; all others are approved for 18 and above. However, none of them are explicitly approved for people over the age of 55, because there is no data to support it.

What is the goal of your study, the DISCO MS trial?

DR. CORBOY: The DISCO MS trial will be the first randomized, controlled, blinded discontinuation trial in the MS space. The objective is to assess the benefit of DMTs in patients over the age of 55.

Part of the rationale for the trial is that prior subgroup analyses have shown that the vast majority of the benefit that we’ve been able to measure with all of these DMTs is seen in those who are under age 45.

A number of studies have examined existing databases and individuals who were either randomly or deliberately taken off of their medication as they age, including people who were felt to be stable with no recent relapses and no recent changes on their MRI brain. These studies reinforced that when discontinuing medications, the individuals who were much more likely to have recurrence of disease activity were younger patients.

Pathological studies clearly show the number of acutely inflamed plaques in the white matter is dramatically lower in autopsies of older vs younger patients. There are different changes in older patients, with lymphocytic nodules in the meninges, gray matter plaques related to these meningeal nodules, microglial activation, and smaller numbers of active, or mostly, inactive, white matter plaques. It’s been difficult to show any substantial benefit in slowing disability progression, much of which is felt to not be associated with acute inflammatory disease in the aging patient. All of these medicines, which can be thought of as anti-inflammatory medicines, are very beneficial when patients are young but less so as they age.

Would you describe the DISCO MS study design?

DR. CORBOY: Our study looks at individuals who are 55 and older who have not had a relapse for at least 5 years, and who’ve not had a change on their brain scan for at least 3 years.

Individuals will be randomized to either stay on the medication that they’re currently taking or discontinue that medicine. They will be followed then for 2 years. The primary outcome will be either a new relapse or a new scan change. The examining investigators are blinded to whether the patient is currently taking a MS disease modifying therapy.

Secondary outcomes include progression of disability as measured by confirmed change on the Extended Disability Status Scale (EDSS).

The enrollment goal is about 300 patients. There are presently 15 sites. The goal is to have the study completed in about 3 years. We’re presently over halfway through enrollment.

We also have a number of patient-reported outcomes because we’re particularly interested in the patient’s view of what’s going on in terms of how they feel. Understanding that dynamic will be extremely important.

We are including both patients with relapsing MS and progressive forms of MS, noting that they should have no relapse and no scan change at study entry.

What are the challenges with this study?

DR. CORBOY: One challenge is interpreting the information with the assumption that the hypothesis is validated. The hypothesis is that in a stable population of older patients that we can safely discontinue DMTs.

If that is found to be true, the question is how many people will be affected? We know that about 46% of people with MS are 55 and older, but there are not really good estimates of the number of individuals 55 and older who remain on a DMT and who are stable by the definition I just described.

It can be safely said, I think, that a substantial number of the individuals 55 and older are still on DMTs. If there’s almost a million people with MS and 46% are 55 and older, that means around 400,000 people with MS in the United States are aged 55 and older. If only half of those are on a DMT, that leaves 200,000. If only half of those are stable and could go off therapy, that would mean perhaps 100,000 people could discontinue DMTs in the United States. If all those assumptions are true, that would be a substantial savings in the health care burden of the United States from a relatively small population of individuals.

Beyond the cost, there are adverse events associated with using these medications. Older patients are more likely to be at risk of complications of MS DMTs. There also are doctor visits, blood monitoring, and other things that are done over time, and the inconvenience of taking a medicine on a routine basis if, indeed, it’s really not necessary because there is no benefit. Moreover, older individuals have other conditions (eg diabetes, hypertension, arrhythmias, cancer, etc) that may limit their ability to use medications due to risk. We’re very interested to see the outcome.

Discontinuing

How would you characterize the prevalence of MS in the elderly?

DR. CORBOY:  A recent large demographic study put together by the National MS Society found that there’s almost a million individuals diagnosed with MS over the course of the last 40 to 50 years. The largest population segment was those aged 55 to 64 years. People with MS aged 55 or older constituted 46% of all those with MS.

What disease-modifying therapies (DMTs) are approved by the FDA for the elderly?

DR. CORBOY: Of the drugs that have received FDA approval, most are for individuals over the age of 18 and there’s no specific age cutoff. However, there’s no data supporting DMT use in people over the age of 55 because they were excluded from the studies.

There’s one DMT, fingolimod, that was approved for use in patients under the age of 18; all others are approved for 18 and above. However, none of them are explicitly approved for people over the age of 55, because there is no data to support it.

What is the goal of your study, the DISCO MS trial?

DR. CORBOY: The DISCO MS trial will be the first randomized, controlled, blinded discontinuation trial in the MS space. The objective is to assess the benefit of DMTs in patients over the age of 55.

Part of the rationale for the trial is that prior subgroup analyses have shown that the vast majority of the benefit that we’ve been able to measure with all of these DMTs is seen in those who are under age 45.

A number of studies have examined existing databases and individuals who were either randomly or deliberately taken off of their medication as they age, including people who were felt to be stable with no recent relapses and no recent changes on their MRI brain. These studies reinforced that when discontinuing medications, the individuals who were much more likely to have recurrence of disease activity were younger patients.

Pathological studies clearly show the number of acutely inflamed plaques in the white matter is dramatically lower in autopsies of older vs younger patients. There are different changes in older patients, with lymphocytic nodules in the meninges, gray matter plaques related to these meningeal nodules, microglial activation, and smaller numbers of active, or mostly, inactive, white matter plaques. It’s been difficult to show any substantial benefit in slowing disability progression, much of which is felt to not be associated with acute inflammatory disease in the aging patient. All of these medicines, which can be thought of as anti-inflammatory medicines, are very beneficial when patients are young but less so as they age.

Would you describe the DISCO MS study design?

DR. CORBOY: Our study looks at individuals who are 55 and older who have not had a relapse for at least 5 years, and who’ve not had a change on their brain scan for at least 3 years.

Individuals will be randomized to either stay on the medication that they’re currently taking or discontinue that medicine. They will be followed then for 2 years. The primary outcome will be either a new relapse or a new scan change. The examining investigators are blinded to whether the patient is currently taking a MS disease modifying therapy.

Secondary outcomes include progression of disability as measured by confirmed change on the Extended Disability Status Scale (EDSS).

The enrollment goal is about 300 patients. There are presently 15 sites. The goal is to have the study completed in about 3 years. We’re presently over halfway through enrollment.

We also have a number of patient-reported outcomes because we’re particularly interested in the patient’s view of what’s going on in terms of how they feel. Understanding that dynamic will be extremely important.

We are including both patients with relapsing MS and progressive forms of MS, noting that they should have no relapse and no scan change at study entry.

What are the challenges with this study?

DR. CORBOY: One challenge is interpreting the information with the assumption that the hypothesis is validated. The hypothesis is that in a stable population of older patients that we can safely discontinue DMTs.

If that is found to be true, the question is how many people will be affected? We know that about 46% of people with MS are 55 and older, but there are not really good estimates of the number of individuals 55 and older who remain on a DMT and who are stable by the definition I just described.

It can be safely said, I think, that a substantial number of the individuals 55 and older are still on DMTs. If there’s almost a million people with MS and 46% are 55 and older, that means around 400,000 people with MS in the United States are aged 55 and older. If only half of those are on a DMT, that leaves 200,000. If only half of those are stable and could go off therapy, that would mean perhaps 100,000 people could discontinue DMTs in the United States. If all those assumptions are true, that would be a substantial savings in the health care burden of the United States from a relatively small population of individuals.

Beyond the cost, there are adverse events associated with using these medications. Older patients are more likely to be at risk of complications of MS DMTs. There also are doctor visits, blood monitoring, and other things that are done over time, and the inconvenience of taking a medicine on a routine basis if, indeed, it’s really not necessary because there is no benefit. Moreover, older individuals have other conditions (eg diabetes, hypertension, arrhythmias, cancer, etc) that may limit their ability to use medications due to risk. We’re very interested to see the outcome.

Discontinuing

How would you characterize the prevalence of MS in the elderly?

DR. CORBOY:  A recent large demographic study put together by the National MS Society found that there’s almost a million individuals diagnosed with MS over the course of the last 40 to 50 years. The largest population segment was those aged 55 to 64 years. People with MS aged 55 or older constituted 46% of all those with MS.

What disease-modifying therapies (DMTs) are approved by the FDA for the elderly?

DR. CORBOY: Of the drugs that have received FDA approval, most are for individuals over the age of 18 and there’s no specific age cutoff. However, there’s no data supporting DMT use in people over the age of 55 because they were excluded from the studies.

There’s one DMT, fingolimod, that was approved for use in patients under the age of 18; all others are approved for 18 and above. However, none of them are explicitly approved for people over the age of 55, because there is no data to support it.

What is the goal of your study, the DISCO MS trial?

DR. CORBOY: The DISCO MS trial will be the first randomized, controlled, blinded discontinuation trial in the MS space. The objective is to assess the benefit of DMTs in patients over the age of 55.

Part of the rationale for the trial is that prior subgroup analyses have shown that the vast majority of the benefit that we’ve been able to measure with all of these DMTs is seen in those who are under age 45.

A number of studies have examined existing databases and individuals who were either randomly or deliberately taken off of their medication as they age, including people who were felt to be stable with no recent relapses and no recent changes on their MRI brain. These studies reinforced that when discontinuing medications, the individuals who were much more likely to have recurrence of disease activity were younger patients.

Pathological studies clearly show the number of acutely inflamed plaques in the white matter is dramatically lower in autopsies of older vs younger patients. There are different changes in older patients, with lymphocytic nodules in the meninges, gray matter plaques related to these meningeal nodules, microglial activation, and smaller numbers of active, or mostly, inactive, white matter plaques. It’s been difficult to show any substantial benefit in slowing disability progression, much of which is felt to not be associated with acute inflammatory disease in the aging patient. All of these medicines, which can be thought of as anti-inflammatory medicines, are very beneficial when patients are young but less so as they age.

Would you describe the DISCO MS study design?

DR. CORBOY: Our study looks at individuals who are 55 and older who have not had a relapse for at least 5 years, and who’ve not had a change on their brain scan for at least 3 years.

Individuals will be randomized to either stay on the medication that they’re currently taking or discontinue that medicine. They will be followed then for 2 years. The primary outcome will be either a new relapse or a new scan change. The examining investigators are blinded to whether the patient is currently taking a MS disease modifying therapy.

Secondary outcomes include progression of disability as measured by confirmed change on the Extended Disability Status Scale (EDSS).

The enrollment goal is about 300 patients. There are presently 15 sites. The goal is to have the study completed in about 3 years. We’re presently over halfway through enrollment.

We also have a number of patient-reported outcomes because we’re particularly interested in the patient’s view of what’s going on in terms of how they feel. Understanding that dynamic will be extremely important.

We are including both patients with relapsing MS and progressive forms of MS, noting that they should have no relapse and no scan change at study entry.

What are the challenges with this study?

DR. CORBOY: One challenge is interpreting the information with the assumption that the hypothesis is validated. The hypothesis is that in a stable population of older patients that we can safely discontinue DMTs.

If that is found to be true, the question is how many people will be affected? We know that about 46% of people with MS are 55 and older, but there are not really good estimates of the number of individuals 55 and older who remain on a DMT and who are stable by the definition I just described.

It can be safely said, I think, that a substantial number of the individuals 55 and older are still on DMTs. If there’s almost a million people with MS and 46% are 55 and older, that means around 400,000 people with MS in the United States are aged 55 and older. If only half of those are on a DMT, that leaves 200,000. If only half of those are stable and could go off therapy, that would mean perhaps 100,000 people could discontinue DMTs in the United States. If all those assumptions are true, that would be a substantial savings in the health care burden of the United States from a relatively small population of individuals.

Beyond the cost, there are adverse events associated with using these medications. Older patients are more likely to be at risk of complications of MS DMTs. There also are doctor visits, blood monitoring, and other things that are done over time, and the inconvenience of taking a medicine on a routine basis if, indeed, it’s really not necessary because there is no benefit. Moreover, older individuals have other conditions (eg diabetes, hypertension, arrhythmias, cancer, etc) that may limit their ability to use medications due to risk. We’re very interested to see the outcome.

DALLAS – Stem cell tourism – the unethical practice of offering unproven cellular preparations to patients for a variety of conditions – is increasingly sought by patients with incurable conditions such as multiple sclerosis and amyotrophic lateral sclerosis, results from a novel survey suggest.

Doug Brunk/MDedge News

In fact, most academic neurologists have been approached by patients with incurable conditions who ask them about stem cell therapy, while about two-thirds have had at least one patient who has undergone stem cell therapy.

“It’s really scary,” Wijdan Rai, MBBS, the study’s first author, said in an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “This is a more prevalent issue than we think, and the complication rates are higher than we think.”

According to the study’s senior author, Jaime Imitola, MD, who directs the Progressive Multiple Sclerosis Multidisciplinary Clinic and Translational Research Program at the Ohio State University Wexner Medical Center, Columbus, the results “call for the creation of a nationwide registry where neurologists can document adverse reactions to stem cell procedures and further support dedicated patient and neurologist education as we have proposed before” (See Semin Neurol. 2018; 38[2]:176-81 and JAMA Neurol. 2015;72[11]:1342-5).


In an effort to understand the experiences and attitudes of academic neurologists regarding stem cell tourism and patient-reported complications, the researchers developed a 25-question survey disseminated via Synapse, a web tool from the American Academy of Neurology. Respondents were asked about demographic information, frequency of patient questioning, perception of physician competence, patient complications and experiences, and attitudes toward increased physician education.

Dr. Rai, who is a senior neurology resident at the medical center, presented findings from 204 neurologist respondents, of whom 31% identified themselves as MS specialists. Nearly all respondents (91%) said they have been approached by patients with incurable conditions seeking information about stem cells (37% of whom had diagnosis of MS). In addition, 65% have had at least one patient that has undergone “stem cell therapy,” and 73% said it would be “helpful” or “very helpful” to have an evidence-based patient education tool on the topic. “Patients most often wanted general information,” Dr. Rai said. “However, 50% requested permission to undergo a stem cell procedure, and 31% approached their neurologist after the procedure.”

Survey respondents reported that 33% of the stem cell interventions were performed in the United States and 22% abroad, while 37% reported both in the U.S. and abroad. Patients underwent the procedures in China, Germany, the Bahamas, Mexico, Russia, and Costa Rica. Three-quarters of respondents (75%) indicated no patient experiencing complications from the stem cell interventions. However, 25% reported patients experiencing a variety of complications from the procedures, including strokes, meningoencephalitis, quadriparesis, MS deterioration, sepsis, hepatitis C, seizures, meningitis from intrathecal cell injections, infections, and spinal cord tumors. “At least three respondents had a patient who died as a direct complication from stem cell therapy,” Dr. Rai said.

In their poster, the researchers recommended a “multipronged approach to improve education of MS patients from exploitation and engaging multiple stakeholders in the field, including MS academic societies, licensing boards, and legislative bodies. Specifically, we call for creation of evidence-based education for both neurologists and patients, including physical resources that neurologists can use when discussing stem cell interventions with patients and videos on proper counseling during these visits.”

Colleagues from OSU’s Laboratory for Neural Stem Cells and Functional Neurogenetics contributed to this work. The researchers reported having no financial disclosures.

[email protected]

SOURCE: Rai W et al. ACTRIMS Forum 2019, Poster 237.

DALLAS – Stem cell tourism – the unethical practice of offering unproven cellular preparations to patients for a variety of conditions – is increasingly sought by patients with incurable conditions such as multiple sclerosis and amyotrophic lateral sclerosis, results from a novel survey suggest.

Doug Brunk/MDedge News

In fact, most academic neurologists have been approached by patients with incurable conditions who ask them about stem cell therapy, while about two-thirds have had at least one patient who has undergone stem cell therapy.

“It’s really scary,” Wijdan Rai, MBBS, the study’s first author, said in an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “This is a more prevalent issue than we think, and the complication rates are higher than we think.”

According to the study’s senior author, Jaime Imitola, MD, who directs the Progressive Multiple Sclerosis Multidisciplinary Clinic and Translational Research Program at the Ohio State University Wexner Medical Center, Columbus, the results “call for the creation of a nationwide registry where neurologists can document adverse reactions to stem cell procedures and further support dedicated patient and neurologist education as we have proposed before” (See Semin Neurol. 2018; 38[2]:176-81 and JAMA Neurol. 2015;72[11]:1342-5).


In an effort to understand the experiences and attitudes of academic neurologists regarding stem cell tourism and patient-reported complications, the researchers developed a 25-question survey disseminated via Synapse, a web tool from the American Academy of Neurology. Respondents were asked about demographic information, frequency of patient questioning, perception of physician competence, patient complications and experiences, and attitudes toward increased physician education.

Dr. Rai, who is a senior neurology resident at the medical center, presented findings from 204 neurologist respondents, of whom 31% identified themselves as MS specialists. Nearly all respondents (91%) said they have been approached by patients with incurable conditions seeking information about stem cells (37% of whom had diagnosis of MS). In addition, 65% have had at least one patient that has undergone “stem cell therapy,” and 73% said it would be “helpful” or “very helpful” to have an evidence-based patient education tool on the topic. “Patients most often wanted general information,” Dr. Rai said. “However, 50% requested permission to undergo a stem cell procedure, and 31% approached their neurologist after the procedure.”

Survey respondents reported that 33% of the stem cell interventions were performed in the United States and 22% abroad, while 37% reported both in the U.S. and abroad. Patients underwent the procedures in China, Germany, the Bahamas, Mexico, Russia, and Costa Rica. Three-quarters of respondents (75%) indicated no patient experiencing complications from the stem cell interventions. However, 25% reported patients experiencing a variety of complications from the procedures, including strokes, meningoencephalitis, quadriparesis, MS deterioration, sepsis, hepatitis C, seizures, meningitis from intrathecal cell injections, infections, and spinal cord tumors. “At least three respondents had a patient who died as a direct complication from stem cell therapy,” Dr. Rai said.

In their poster, the researchers recommended a “multipronged approach to improve education of MS patients from exploitation and engaging multiple stakeholders in the field, including MS academic societies, licensing boards, and legislative bodies. Specifically, we call for creation of evidence-based education for both neurologists and patients, including physical resources that neurologists can use when discussing stem cell interventions with patients and videos on proper counseling during these visits.”

Colleagues from OSU’s Laboratory for Neural Stem Cells and Functional Neurogenetics contributed to this work. The researchers reported having no financial disclosures.

[email protected]

SOURCE: Rai W et al. ACTRIMS Forum 2019, Poster 237.

DALLAS – Stem cell tourism – the unethical practice of offering unproven cellular preparations to patients for a variety of conditions – is increasingly sought by patients with incurable conditions such as multiple sclerosis and amyotrophic lateral sclerosis, results from a novel survey suggest.

Doug Brunk/MDedge News

In fact, most academic neurologists have been approached by patients with incurable conditions who ask them about stem cell therapy, while about two-thirds have had at least one patient who has undergone stem cell therapy.

“It’s really scary,” Wijdan Rai, MBBS, the study’s first author, said in an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “This is a more prevalent issue than we think, and the complication rates are higher than we think.”

According to the study’s senior author, Jaime Imitola, MD, who directs the Progressive Multiple Sclerosis Multidisciplinary Clinic and Translational Research Program at the Ohio State University Wexner Medical Center, Columbus, the results “call for the creation of a nationwide registry where neurologists can document adverse reactions to stem cell procedures and further support dedicated patient and neurologist education as we have proposed before” (See Semin Neurol. 2018; 38[2]:176-81 and JAMA Neurol. 2015;72[11]:1342-5).


In an effort to understand the experiences and attitudes of academic neurologists regarding stem cell tourism and patient-reported complications, the researchers developed a 25-question survey disseminated via Synapse, a web tool from the American Academy of Neurology. Respondents were asked about demographic information, frequency of patient questioning, perception of physician competence, patient complications and experiences, and attitudes toward increased physician education.

Dr. Rai, who is a senior neurology resident at the medical center, presented findings from 204 neurologist respondents, of whom 31% identified themselves as MS specialists. Nearly all respondents (91%) said they have been approached by patients with incurable conditions seeking information about stem cells (37% of whom had diagnosis of MS). In addition, 65% have had at least one patient that has undergone “stem cell therapy,” and 73% said it would be “helpful” or “very helpful” to have an evidence-based patient education tool on the topic. “Patients most often wanted general information,” Dr. Rai said. “However, 50% requested permission to undergo a stem cell procedure, and 31% approached their neurologist after the procedure.”

Survey respondents reported that 33% of the stem cell interventions were performed in the United States and 22% abroad, while 37% reported both in the U.S. and abroad. Patients underwent the procedures in China, Germany, the Bahamas, Mexico, Russia, and Costa Rica. Three-quarters of respondents (75%) indicated no patient experiencing complications from the stem cell interventions. However, 25% reported patients experiencing a variety of complications from the procedures, including strokes, meningoencephalitis, quadriparesis, MS deterioration, sepsis, hepatitis C, seizures, meningitis from intrathecal cell injections, infections, and spinal cord tumors. “At least three respondents had a patient who died as a direct complication from stem cell therapy,” Dr. Rai said.

In their poster, the researchers recommended a “multipronged approach to improve education of MS patients from exploitation and engaging multiple stakeholders in the field, including MS academic societies, licensing boards, and legislative bodies. Specifically, we call for creation of evidence-based education for both neurologists and patients, including physical resources that neurologists can use when discussing stem cell interventions with patients and videos on proper counseling during these visits.”

Colleagues from OSU’s Laboratory for Neural Stem Cells and Functional Neurogenetics contributed to this work. The researchers reported having no financial disclosures.

[email protected]

SOURCE: Rai W et al. ACTRIMS Forum 2019, Poster 237.

DALLAS – The way Lilyana Amezcua, MD, sees it, clinicians should view race and ethnicity as health disparities when assessing individuals with multiple sclerosis.

Whites are predominately affected with MS, “but we have seen changing demographics,” said Dr. Amezcua, of the University of Southern California MS Comprehensive Care and Research Group. “Why are African Americans now at higher risk ... and why do African Americans appear to have more severe disease? Is it a biological difference ... or is it because of poor access” to health care?

At the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, Dr. Amezcua delivered a presentation entitled “Effect of Race and Ethnicity on MS Presentation and Disease Course.” She called on researchers in the field “to not just take race and ethnicity as any small variable. We need to be cognizant and use the correct methodology, depending on what [question] we want to answer. We need to better define how we ascertain race, how we ascertain ethnicity.”

Dr. Amezcua, who is also the MS fellowship program director at the Keck School of Medicine, disclosed that she receives funding from the National MS Society, the National Institutes of Health, the California Community Foundation, and Biogen.

[email protected]

DALLAS – The way Lilyana Amezcua, MD, sees it, clinicians should view race and ethnicity as health disparities when assessing individuals with multiple sclerosis.

Whites are predominately affected with MS, “but we have seen changing demographics,” said Dr. Amezcua, of the University of Southern California MS Comprehensive Care and Research Group. “Why are African Americans now at higher risk ... and why do African Americans appear to have more severe disease? Is it a biological difference ... or is it because of poor access” to health care?

At the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, Dr. Amezcua delivered a presentation entitled “Effect of Race and Ethnicity on MS Presentation and Disease Course.” She called on researchers in the field “to not just take race and ethnicity as any small variable. We need to be cognizant and use the correct methodology, depending on what [question] we want to answer. We need to better define how we ascertain race, how we ascertain ethnicity.”

Dr. Amezcua, who is also the MS fellowship program director at the Keck School of Medicine, disclosed that she receives funding from the National MS Society, the National Institutes of Health, the California Community Foundation, and Biogen.

[email protected]

DALLAS – The way Lilyana Amezcua, MD, sees it, clinicians should view race and ethnicity as health disparities when assessing individuals with multiple sclerosis.

Whites are predominately affected with MS, “but we have seen changing demographics,” said Dr. Amezcua, of the University of Southern California MS Comprehensive Care and Research Group. “Why are African Americans now at higher risk ... and why do African Americans appear to have more severe disease? Is it a biological difference ... or is it because of poor access” to health care?

At the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, Dr. Amezcua delivered a presentation entitled “Effect of Race and Ethnicity on MS Presentation and Disease Course.” She called on researchers in the field “to not just take race and ethnicity as any small variable. We need to be cognizant and use the correct methodology, depending on what [question] we want to answer. We need to better define how we ascertain race, how we ascertain ethnicity.”

Dr. Amezcua, who is also the MS fellowship program director at the Keck School of Medicine, disclosed that she receives funding from the National MS Society, the National Institutes of Health, the California Community Foundation, and Biogen.

[email protected]

DALLAS – Patients with multiple sclerosis (MS) have elevated levels of specific clusters of cerebrospinal fluid (CSF) biomarkers related to astrocytes and microglia that correlated with disease severity in a blinded analysis of more than 1,000 proteins from the CSF of more than 400 patients with neuroimmunologic disease and healthy volunteers.

Jake Remaly/MDedge News

Previous studies have indicated that aberrant activation of astrocytes and microglia underlies disability progression in older patients with MS, but researchers have lacked biomarkers of these processes in living subjects. In a presentation at a meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, Ruturaj R. Masvekar, PhD, described developing biomarkers of CNS cell–specific processes and examining how they relate to MS disability progression. Dr. Masvekar, a researcher at the National Institute of Allergy and Infectious Diseases, and his coinvestigators used a modified DNA aptamer assay to measure proteins in the CSF of 431 patients with neuroimmunologic diseases and healthy volunteers, followed by variable cluster analysis and in vitro modeling to define 64 clusters of CSF biomarkers that relate to CNS cell types.

The study included 42 healthy donors, 20 patients with clinically isolated syndrome, 57 patients with noninflammatory neurologic disorders, 127 patients with relapsing-remitting MS, 72 patients with secondary progressive MS, and 113 patients with primary progressive MS. In a training cohort of 217 participants, the researchers assessed how biomarkers differed between the diagnostic categories. The researchers then validated the results in an independent cohort of 214 participants.

One astrocyte-related cluster (MMP7, SERPINA3, GZMA, and CLIC1) and one microglia-related cluster (DSG2 and TNFRSF25) was significantly elevated in all MS subgroups, compared with healthy controls and patients with noninflammatory neurologic disorders.

In addition, these clusters “significantly correlated with clinical measures of disability, CNS tissue destruction, and MS severity,” Dr. Masvekar said.

The microglial cluster was significantly elevated in all MS subgroups, whereas neuronal endothelial, astrocytic, and oligodendroglial biomarker clusters were elevated only in patients with progressive MS.

“Microglial activation is present in all stages of MS, while toxic astrogliosis increases with MS duration, concomitantly with neuronal and oligodendroglial degeneration,” Dr. Masvekar said. “Microglial activation and toxic astrogliosis likely partake in CNS tissue destruction and enhance MS severity.”

This study, which was recently published in Multiple Sclerosis and Related Disorders (2019 Feb;28:34-43), was supported by the intramural research program at NIAID.

[email protected]

SOURCE: Masvekar RR et al. ACTRIMS Forum 2019, Abstract 281.

DALLAS – Patients with multiple sclerosis (MS) have elevated levels of specific clusters of cerebrospinal fluid (CSF) biomarkers related to astrocytes and microglia that correlated with disease severity in a blinded analysis of more than 1,000 proteins from the CSF of more than 400 patients with neuroimmunologic disease and healthy volunteers.

Jake Remaly/MDedge News

Previous studies have indicated that aberrant activation of astrocytes and microglia underlies disability progression in older patients with MS, but researchers have lacked biomarkers of these processes in living subjects. In a presentation at a meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, Ruturaj R. Masvekar, PhD, described developing biomarkers of CNS cell–specific processes and examining how they relate to MS disability progression. Dr. Masvekar, a researcher at the National Institute of Allergy and Infectious Diseases, and his coinvestigators used a modified DNA aptamer assay to measure proteins in the CSF of 431 patients with neuroimmunologic diseases and healthy volunteers, followed by variable cluster analysis and in vitro modeling to define 64 clusters of CSF biomarkers that relate to CNS cell types.

The study included 42 healthy donors, 20 patients with clinically isolated syndrome, 57 patients with noninflammatory neurologic disorders, 127 patients with relapsing-remitting MS, 72 patients with secondary progressive MS, and 113 patients with primary progressive MS. In a training cohort of 217 participants, the researchers assessed how biomarkers differed between the diagnostic categories. The researchers then validated the results in an independent cohort of 214 participants.

One astrocyte-related cluster (MMP7, SERPINA3, GZMA, and CLIC1) and one microglia-related cluster (DSG2 and TNFRSF25) was significantly elevated in all MS subgroups, compared with healthy controls and patients with noninflammatory neurologic disorders.

In addition, these clusters “significantly correlated with clinical measures of disability, CNS tissue destruction, and MS severity,” Dr. Masvekar said.

The microglial cluster was significantly elevated in all MS subgroups, whereas neuronal endothelial, astrocytic, and oligodendroglial biomarker clusters were elevated only in patients with progressive MS.

“Microglial activation is present in all stages of MS, while toxic astrogliosis increases with MS duration, concomitantly with neuronal and oligodendroglial degeneration,” Dr. Masvekar said. “Microglial activation and toxic astrogliosis likely partake in CNS tissue destruction and enhance MS severity.”

This study, which was recently published in Multiple Sclerosis and Related Disorders (2019 Feb;28:34-43), was supported by the intramural research program at NIAID.

[email protected]

SOURCE: Masvekar RR et al. ACTRIMS Forum 2019, Abstract 281.

DALLAS – Patients with multiple sclerosis (MS) have elevated levels of specific clusters of cerebrospinal fluid (CSF) biomarkers related to astrocytes and microglia that correlated with disease severity in a blinded analysis of more than 1,000 proteins from the CSF of more than 400 patients with neuroimmunologic disease and healthy volunteers.

Jake Remaly/MDedge News

Previous studies have indicated that aberrant activation of astrocytes and microglia underlies disability progression in older patients with MS, but researchers have lacked biomarkers of these processes in living subjects. In a presentation at a meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis, Ruturaj R. Masvekar, PhD, described developing biomarkers of CNS cell–specific processes and examining how they relate to MS disability progression. Dr. Masvekar, a researcher at the National Institute of Allergy and Infectious Diseases, and his coinvestigators used a modified DNA aptamer assay to measure proteins in the CSF of 431 patients with neuroimmunologic diseases and healthy volunteers, followed by variable cluster analysis and in vitro modeling to define 64 clusters of CSF biomarkers that relate to CNS cell types.

The study included 42 healthy donors, 20 patients with clinically isolated syndrome, 57 patients with noninflammatory neurologic disorders, 127 patients with relapsing-remitting MS, 72 patients with secondary progressive MS, and 113 patients with primary progressive MS. In a training cohort of 217 participants, the researchers assessed how biomarkers differed between the diagnostic categories. The researchers then validated the results in an independent cohort of 214 participants.

One astrocyte-related cluster (MMP7, SERPINA3, GZMA, and CLIC1) and one microglia-related cluster (DSG2 and TNFRSF25) was significantly elevated in all MS subgroups, compared with healthy controls and patients with noninflammatory neurologic disorders.

In addition, these clusters “significantly correlated with clinical measures of disability, CNS tissue destruction, and MS severity,” Dr. Masvekar said.

The microglial cluster was significantly elevated in all MS subgroups, whereas neuronal endothelial, astrocytic, and oligodendroglial biomarker clusters were elevated only in patients with progressive MS.

“Microglial activation is present in all stages of MS, while toxic astrogliosis increases with MS duration, concomitantly with neuronal and oligodendroglial degeneration,” Dr. Masvekar said. “Microglial activation and toxic astrogliosis likely partake in CNS tissue destruction and enhance MS severity.”

This study, which was recently published in Multiple Sclerosis and Related Disorders (2019 Feb;28:34-43), was supported by the intramural research program at NIAID.

[email protected]

SOURCE: Masvekar RR et al. ACTRIMS Forum 2019, Abstract 281.

DALLAS – A battery of smartphone-based tests has been developed to help detect visual pathway disturbances in MS patients and to follow them over time.

“One of the ideas is, can you design something that’s so easy to use and quick that it’s not a burden on the patient?” Randy H. Kardon, MD, PhD, said in an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “The other was to test a couple of different modalities. By that I mean we test visual acuity, contrast sensitivity, and critical flicker fusion, which is a way of measuring the speed of conduction of nerves in the visual system.”

Dr. Kardon, professor of neuro-ophthalmology at the University of Iowa, Iowa City, worked with colleagues from Aalborg University, Denmark, to study these tests and a novel measure known as the vanishing optotype on 117 patients with MS and 103 age-matched controls. They found that the tests “very nicely discriminated between normal eyes from patients that had MS,” said Dr. Kardon, director of the Iowa City VA Center for Prevention and Treatment of Visual Loss. “Furthermore, we could determine which eyes from the MS patients had previous optic neuritis and which eyes hadn’t. We’re now looking for partners to go forward with larger studies to validate it further and refine these tests even more.”

Dr. Kardon disclosed that he has received funding from the National Eye Institute, the Department of Defense, and from VA Rehabilitation Research and Development. He was also a member of the Novartis steering committee for the OCTiMS study and is a cofounder of MedFace and FaceX.

[email protected]

DALLAS – A battery of smartphone-based tests has been developed to help detect visual pathway disturbances in MS patients and to follow them over time.

“One of the ideas is, can you design something that’s so easy to use and quick that it’s not a burden on the patient?” Randy H. Kardon, MD, PhD, said in an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “The other was to test a couple of different modalities. By that I mean we test visual acuity, contrast sensitivity, and critical flicker fusion, which is a way of measuring the speed of conduction of nerves in the visual system.”

Dr. Kardon, professor of neuro-ophthalmology at the University of Iowa, Iowa City, worked with colleagues from Aalborg University, Denmark, to study these tests and a novel measure known as the vanishing optotype on 117 patients with MS and 103 age-matched controls. They found that the tests “very nicely discriminated between normal eyes from patients that had MS,” said Dr. Kardon, director of the Iowa City VA Center for Prevention and Treatment of Visual Loss. “Furthermore, we could determine which eyes from the MS patients had previous optic neuritis and which eyes hadn’t. We’re now looking for partners to go forward with larger studies to validate it further and refine these tests even more.”

Dr. Kardon disclosed that he has received funding from the National Eye Institute, the Department of Defense, and from VA Rehabilitation Research and Development. He was also a member of the Novartis steering committee for the OCTiMS study and is a cofounder of MedFace and FaceX.

[email protected]

DALLAS – A battery of smartphone-based tests has been developed to help detect visual pathway disturbances in MS patients and to follow them over time.

“One of the ideas is, can you design something that’s so easy to use and quick that it’s not a burden on the patient?” Randy H. Kardon, MD, PhD, said in an interview at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “The other was to test a couple of different modalities. By that I mean we test visual acuity, contrast sensitivity, and critical flicker fusion, which is a way of measuring the speed of conduction of nerves in the visual system.”

Dr. Kardon, professor of neuro-ophthalmology at the University of Iowa, Iowa City, worked with colleagues from Aalborg University, Denmark, to study these tests and a novel measure known as the vanishing optotype on 117 patients with MS and 103 age-matched controls. They found that the tests “very nicely discriminated between normal eyes from patients that had MS,” said Dr. Kardon, director of the Iowa City VA Center for Prevention and Treatment of Visual Loss. “Furthermore, we could determine which eyes from the MS patients had previous optic neuritis and which eyes hadn’t. We’re now looking for partners to go forward with larger studies to validate it further and refine these tests even more.”

Dr. Kardon disclosed that he has received funding from the National Eye Institute, the Department of Defense, and from VA Rehabilitation Research and Development. He was also a member of the Novartis steering committee for the OCTiMS study and is a cofounder of MedFace and FaceX.

[email protected]

DALLAS – The rate of spinal cord atrophy at the C1 level is promising as a prognostic biomarker for the future conversion to secondary progressive disease in patients with relapsing remitting multiple sclerosis (RRMS), results from a novel, single-center study suggest.

“Among all magnetic resonance imaging measures, spinal cord area shows the strongest correlations with MS disability and has been shown to discriminate progressive from relapsing remitting disease subtypes,” lead study author Antje Bischof, MD, said in an interview in advance of the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “In our work, we used a novel method to accurately measure upper cervical cord area at C1 vertebral level from brain MRI. This enabled us to show for the first time that spinal cord atrophy rates are faster in relapsing remitting MS patients who later converted to secondary progressive disease, compared to a matched group of patients who remained relapsing remitting MS over 2 decades.”


Dr. Bischof, a postdoctoral research fellow in the department of neurology at the University of California, San Francisco, and her colleagues matched 54 RRMS patients who converted to secondary progressive MS (SPMS) during the 12-year observation period with 54 RRMS patients who remained RRMS during the observation period, based on demographic and clinical criteria. Additionally, they evaluated 54 age- and sex-matched healthy controls at baseline. From routine T1-weighted brain MRI, they analyzed brain measures and spinal cord area at C1 level over 12 years to evaluate their potential to discriminate between the two matched groups during the preconversion period.

Subjects who developed SPMS showed higher rates of spinal cord atrophy (–2.2% per year; standard error, 0.2) before conversion to a secondary progressive course, compared with their RRMS matches who did not convert to SPMS (–0.7% per year; SE, 0.2; P less than .0001). Their data suggest that this difference exists at least 4 years before conversion to SPMS. “None of the commonly used measures of the brain including global brain volumes like white matter and gray matter, regional brain volumes like thalamus, and MS lesion volumes, discriminated between the patients with relapsing remitting MS who later converted to secondary progressive disease and the patients who remained RRMS,” Dr. Bischof said.

She acknowledged certain limitations of the study, including the small sample size and the fact that the results require confirmation in a second MS cohort in order to be generalizable. “These results suggest cervical cord atrophy rate at C1 level as a prognostic biomarker for the conversion to secondary progressive MS and could be useful for treatment decisions early in the disease course, and for the study of genetic, epidemiologic, and immune variables in MS,” Dr. Bischof concluded.

She reported having no financial disclosures.

[email protected]

SOURCE: Bischof A et al. ACTRIMS Forum 2019, Abstract P157.

DALLAS – The rate of spinal cord atrophy at the C1 level is promising as a prognostic biomarker for the future conversion to secondary progressive disease in patients with relapsing remitting multiple sclerosis (RRMS), results from a novel, single-center study suggest.

“Among all magnetic resonance imaging measures, spinal cord area shows the strongest correlations with MS disability and has been shown to discriminate progressive from relapsing remitting disease subtypes,” lead study author Antje Bischof, MD, said in an interview in advance of the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “In our work, we used a novel method to accurately measure upper cervical cord area at C1 vertebral level from brain MRI. This enabled us to show for the first time that spinal cord atrophy rates are faster in relapsing remitting MS patients who later converted to secondary progressive disease, compared to a matched group of patients who remained relapsing remitting MS over 2 decades.”


Dr. Bischof, a postdoctoral research fellow in the department of neurology at the University of California, San Francisco, and her colleagues matched 54 RRMS patients who converted to secondary progressive MS (SPMS) during the 12-year observation period with 54 RRMS patients who remained RRMS during the observation period, based on demographic and clinical criteria. Additionally, they evaluated 54 age- and sex-matched healthy controls at baseline. From routine T1-weighted brain MRI, they analyzed brain measures and spinal cord area at C1 level over 12 years to evaluate their potential to discriminate between the two matched groups during the preconversion period.

Subjects who developed SPMS showed higher rates of spinal cord atrophy (–2.2% per year; standard error, 0.2) before conversion to a secondary progressive course, compared with their RRMS matches who did not convert to SPMS (–0.7% per year; SE, 0.2; P less than .0001). Their data suggest that this difference exists at least 4 years before conversion to SPMS. “None of the commonly used measures of the brain including global brain volumes like white matter and gray matter, regional brain volumes like thalamus, and MS lesion volumes, discriminated between the patients with relapsing remitting MS who later converted to secondary progressive disease and the patients who remained RRMS,” Dr. Bischof said.

She acknowledged certain limitations of the study, including the small sample size and the fact that the results require confirmation in a second MS cohort in order to be generalizable. “These results suggest cervical cord atrophy rate at C1 level as a prognostic biomarker for the conversion to secondary progressive MS and could be useful for treatment decisions early in the disease course, and for the study of genetic, epidemiologic, and immune variables in MS,” Dr. Bischof concluded.

She reported having no financial disclosures.

[email protected]

SOURCE: Bischof A et al. ACTRIMS Forum 2019, Abstract P157.

DALLAS – The rate of spinal cord atrophy at the C1 level is promising as a prognostic biomarker for the future conversion to secondary progressive disease in patients with relapsing remitting multiple sclerosis (RRMS), results from a novel, single-center study suggest.

“Among all magnetic resonance imaging measures, spinal cord area shows the strongest correlations with MS disability and has been shown to discriminate progressive from relapsing remitting disease subtypes,” lead study author Antje Bischof, MD, said in an interview in advance of the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “In our work, we used a novel method to accurately measure upper cervical cord area at C1 vertebral level from brain MRI. This enabled us to show for the first time that spinal cord atrophy rates are faster in relapsing remitting MS patients who later converted to secondary progressive disease, compared to a matched group of patients who remained relapsing remitting MS over 2 decades.”


Dr. Bischof, a postdoctoral research fellow in the department of neurology at the University of California, San Francisco, and her colleagues matched 54 RRMS patients who converted to secondary progressive MS (SPMS) during the 12-year observation period with 54 RRMS patients who remained RRMS during the observation period, based on demographic and clinical criteria. Additionally, they evaluated 54 age- and sex-matched healthy controls at baseline. From routine T1-weighted brain MRI, they analyzed brain measures and spinal cord area at C1 level over 12 years to evaluate their potential to discriminate between the two matched groups during the preconversion period.

Subjects who developed SPMS showed higher rates of spinal cord atrophy (–2.2% per year; standard error, 0.2) before conversion to a secondary progressive course, compared with their RRMS matches who did not convert to SPMS (–0.7% per year; SE, 0.2; P less than .0001). Their data suggest that this difference exists at least 4 years before conversion to SPMS. “None of the commonly used measures of the brain including global brain volumes like white matter and gray matter, regional brain volumes like thalamus, and MS lesion volumes, discriminated between the patients with relapsing remitting MS who later converted to secondary progressive disease and the patients who remained RRMS,” Dr. Bischof said.

She acknowledged certain limitations of the study, including the small sample size and the fact that the results require confirmation in a second MS cohort in order to be generalizable. “These results suggest cervical cord atrophy rate at C1 level as a prognostic biomarker for the conversion to secondary progressive MS and could be useful for treatment decisions early in the disease course, and for the study of genetic, epidemiologic, and immune variables in MS,” Dr. Bischof concluded.

She reported having no financial disclosures.

[email protected]

SOURCE: Bischof A et al. ACTRIMS Forum 2019, Abstract P157.