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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_2745_Библиотеки_им_академика_М_И_Перельмана
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Treatment
The treatment of pediatric patients with MS follows the
following tenets
21-24
:
Institute a disease-modifying treatment (DMT) as soon as
the diagnosis of pediatric MS is confirmed. This is a
highly relapsing form of disease, and early effective
treatment may prevent relapses and relapse-associated
disability (Table 20.4). Consideration of a highly
effective DMT balancing safety and tolerability is
important in this population.
Monitor DMT response clinically and with annual MRI
scans.
25
Appropriate bloodwork, screening, and
monitoring tests may be required for each DMT.
Monitor adherence to therapy continually. Adherence
may be challenging in the setting of miseducation about
the expectations for DMTs, unaddressed side effects,
busy family schedules, and travel/college. 26 In the case of
nonadherence, schedule a visit to discuss and address
contributing issues and consider switching if not
addressable.
Switch treatment if there is evidence of intractable
nonadherence, intolerance, or treatment failure.
27
Treatment failure may be defined 1 to 2 new lesions or
attacks occurring within a 12-month period. One must
account for an approximately 3-month period for a new
DMT to take effect, and consider a rebaselined MRI at
that time. The tolerance for new lesions or attacks versus
switching is a discussion between the neurologist and
family, with an informed discussion about the risks or
benefits of either approach.
Consider symptomatic treatments as needed. These may
include antidepressants, fatigue medications, and bladder
management.
Consider contraceptives in sexually active teenagers. This
may be a challenging conversation, but important,
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because many DMTs may have adverse effects on a
pregnancy and some are teratogens.
Table 20.4
Options for Disease-Modifying Treatments in Pediatric MS
Level of Evidence Potential Side Effects
Fingolimod (oral) FDA approved for pediatric MS
(2018) based on phase II
randomized controlled trial
(Chitnis, NEJM in press)
Bradycardia, macular
edema, infections
Beta-interferon1a and beta-
interferon-1b (im
or sc injections)
EMA approval for children
>12 y of age. Retrospective
observational studies
29,30
Injection site reactions,
flulike symptoms,
depression
Glatiramer
acetate (sc
injections)
Retrospective observational
studies
Injection site reactions,
postinjection tachycardia
Natalizumab
(intravenous
infusion)
Prospective observational
studies
31,32
Progressive multifocal
leukoencephalopathy,
infusion reactions
Rituximab
(intravenous
infusion)
Observational studies
33-35
Infusion reactions,
infections,
hypogammaglobulinemia
EMA, European Medicines Agency; FDA, US Food and Drug
Administration; MS, multiple sclerosis.
There are additional drugs under study for the treatment of
pediatric MS, including dimethyl fumarate, teriflunomide, and
alemtuzumab, with results anticipated in 2019 to 2020.
24,28
Transitional Care and College Planning
Most children with MS will receive a diagnosis during their
teenage years and thus may be eligible to transition to adult
care within a few years after diagnosis. Our practice is to
continue to follow these patients in the pediatric setting up to
age 20 to 23 years to provide educational and psychosocial
support during this critical period. Transitions to an adult
neurologist should include continuation or transition of key
support services including school support, psychosocial care,
and subspecialty care (urology, physical therapy). Often,
meeting with the adult neurologist before transition helps to
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ease the anxiety of a new clinical setting. Young adults are
encouraged to start to participate in their own care early onset
and includes making appointments, monitoring medication
adherence, and filling prescriptions.
Transition to college requires preparation and consideration of
the specific needs of a young adult with MS. Discussion with
the patient and family should include consideration of college
location, proximity to medical/neurological care, dormitory
conditions including privacy, temperature control, and the
ability to administer medications. Most colleges have an
American for Disabilities Act (ADA) office on campus, and
patients with MS should be encouraged to establish a
relationship with the ADA office, which can provide academic
and legal support.
Resources for Families
There are a number of organizations that offer resources to
assist and support children and families affected by pediatric
MS. These include the International Pediatric MS Study Group
(www.ipmssg.org), the National MS Society (www.nmss.org),
and other national organizations.
References
Belman AL, Krupp LB, Olsen CS, et al. Characteristics of children and adolescents
with multiple sclerosis. Pediatrics. 2016;138(1):e20160120.
Chitnis T. Role of puberty in multiple sclerosis risk and course. Clin Immunol.
2013;149:192-200.
Chitnis T, Graves J, Weinstock-Guttman B, et al. Distinct effects of obesity and
puberty on risk and age at onset of pediatric MS. Ann Clin Transl Neurol.
2016;3:897-907.
Chitnis T, Glanz B, Jaffin S, Healy B. Demographics of pediatric-onset multiple
sclerosis in an MS center population from the Northeastern United States. Mult
Scler. 2009;15:627-631.
Waldman A, Ness J, Pohl D, et al. Pediatric multiple sclerosis: clinical features and
outcome. Neurology. 2016;87:S74-S81.
Wingerchuk DM, Banwell B, Bennett JL, et al. International consensus diagnostic
criteria for neuromyelitis optica spectrum disorders. Neurology. 2015;85:177-
189.
Marrie RA, O’Mahony J, Maxwell C, et al. Incidence and prevalence of MS in
children: a population-based study in Ontario, Canada. Neurology.
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2018;91(17):e1579-e1590.
Krupp LB, Tardieu M, Amato MP, et al. International Pediatric Multiple Sclerosis
Study Group criteria for pediatric multiple sclerosis and immune-mediated
central nervous system demyelinating disorders: revisions to the 2007
definitions. Mult Scler. 2013;19:1261-1267.
Pohl D, Alper G, Van Haren K, et al. Acute disseminated encephalomyelitis:
updates on an inflammatory CNS syndrome. Neurology. 2016;87:S38-S45.
Chitnis T, Ness J, Krupp L, et al. Clinical features of neuromyelitis optica in
children: US Network of Pediatric MS Centers report. Neurology. 2016;86:245-
252.
Fernandez-Carbonell C, Vargas-Lowy D, Musallam A, et al. Clinical and MRI
phenotype of children with MOG antibodies. Mult Scler. 2016;22:174-184.
Ramanathan S, Dale RC, Brilot F. Anti-MOG antibody: the history, clinical
phenotype, and pathogenicity of a serum biomarker for demyelination.
Autoimmun Rev. 2016;15:307-324.
Probstel AK, Dornmair K, Bittner R, et al. Antibodies to MOG are transient in
childhood acute disseminated encephalomyelitis. Neurology. 2011;77:580-588.
Benson LA, Healy BC, Gorman MP, et al. Elevated relapse rates in pediatric
compared to adult MS persist for at least 6 years. Mult Scler Relat Disord.
2014;3:186-193.
Gorman MP, Healy BC, Polgar-Turcsanyi M, Chitnis T. Increased relapse rate in
pediatric-onset compared with adult-onset multiple sclerosis. Arch Neurol.
2009;66:54-59.
Fernandez Carbonell C, Benson L, Rintell D, Prince J, Chitnis T. Functional
relapses in pediatric multiple sclerosis. J Child Neurol. 2014;29:943-946.
Pakpoor J, Goldacre R, Schmierer K, Giovannoni G, Waubant E, Goldacre MJ.
Psychiatric disorders in children with demyelinating diseases of the central
nervous system. Mult Scler. 2017. doi:10.1177/1352458517719150.
Amato MP, Krupp LB, Charvet LE, Penner I, Till C. Pediatric multiple sclerosis:
cognition and mood. Neurology. 2016;87:S82-S87.
Charvet LE, Cleary RE, Vazquez K, Belman AL, Krupp LB; MS USNfP . Social
cognition in pediatric-onset multiple sclerosis (MS). Mult Scler. 2014;20:1478-
1484.
Waldman AT, Hiremath G, Avery RA, et al. Monocular and binocular low-contrast
visual acuity and optical coherence tomography in pediatric multiple sclerosis.
Mult Scler Relat Disord. 2013;3:326-334.
Chitnis T. Disease-modifying therapy of pediatric multiple sclerosis.
Neurotherapeutics. 2013;10:89-96.
Chitnis T, Ghezzi A, Bajer-Kornek B, Boyko A, Giovannoni G, Pohl D. Pediatric
multiple sclerosis: escalation and emerging treatments. Neurology.
2016;87:S103-S109.
Chitnis T, Krupp L, Yeh A, et al. Pediatric multiple sclerosis. Neurol Clin.
2011;29:481-505.
Simone M, Chitnis T. Use of disease-modifying therapies in pediatric MS. Curr
Treat Options Neurol. 2016;18:36.
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Banwell B, Arnold DL, Tillema JM, et al. MRI in the evaluation of pediatric
multiple sclerosis. Neurology. 2016;87:S88-S96.
Schwartz CE, Grover SA, Powell VE, et al. Risk factors for non-adherence to
disease-modifying therapy in pediatric multiple sclerosis. Mult Scler.
2018;24:175-185.
Yeh EA, Waubant E, Krupp LB, et al. Multiple sclerosis therapies in pediatric
patients with refractory multiple sclerosis. Arch Neurol. 2011;68:437-444.
Chitnis T, Tardieu M, Amato MP, et al. International pediatric MS study group
clinical trials summit: meeting report. Neurology. 2013;80:1161-1168.
Tenembaum SN, Banwell B, Pohl D, et al. Subcutaneous interferon Beta-1a in
pediatric multiple sclerosis: a retrospective study. J Child Neurol. 2013;28:849-
856.
Krupp LB, Pohl D, Ghezzi A, et al. Subcutaneous interferon beta-1a in pediatric
patients with multiple sclerosis: regional differences in clinical features, disease
management, and treatment outcomes in an international retrospective study. J
Neurol Sci. 2016;363:33-38.
Ghezzi A, Moiola L, Pozzilli C, et al. Natalizumab in the pediatric MS population:
results of the Italian registry. BMC Neurol. 2015;15:174.
Ghezzi A, Pozzilli C, Grimaldi LM, et al. Natalizumab in pediatric multiple
sclerosis: results of a cohort of 55 cases. Mult Scler. 2013;19:1106-1112.
Nosadini M, Alper G, Riney CJ, et al. Rituximab monitoring and redosing in
pediatric neuromyelitis optica spectrum disorder. Neurol Neuroimmunol
Neuroinflamm. 2016;3:e188.
Dale RC, Brilot F, Duffy LV, et al. Utility and safety of rituximab in pediatric
autoimmune and inflammatory CNS disease. Neurology. 2014;83:142-150.
Chitnis T, Waubant E. B-cell depletion in children with neuroimmunologic
conditions: the learning curve. Neurology. 2014;83:111-112.
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C H A P T E R 2 1
Dental and Oral Health
Considerations in Multiple
Sclerosis
Danielle E. Currier Gwendolyn S. Reeve Marsha E. Rubin
Introduction
Dental clinicians are essential members of every patient’s
health care team. They play an integral role in prevention,
diagnosis, and treatment to ensure that oral health impacts the
overall health of patients positively. Long-term challenges of
multiple sclerosis (MS) have implications in the motor,
sensory, and cognitive functions of these patients. The ability
to maintain proper hygiene, control medication-induced
changes in the oral environment, prevent infection, and
preserve function can greatly affect the well-being of the
patient beyond the context of their oral health.
An understanding of common symptoms associated with MS
is essential. Temporomandibular disorders, parafunctional
habits, facial palsies, and dysphagia are commonly seen
among these patients. To a lesser but still significant extent,
paroxysmal pain syndromes such as trigeminal neuralgia (TN)
can affect individuals with MS.
1-3
These symptoms should be
distinguished from symptoms of a dental origin, and in some
instances, they can be the first sign of MS in the undiagnosed
patient. When a dental source cannot be identified, the patient
should be referred to a specialist for medical workup. The oral
health care provider should help reduce pain, diagnose
infections early on, and educate the patient on individualized
long-term dental care.
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This chapter will discuss ways the oral health care provider
should be involved with the treatment and management of
patients with MS from the start of their care. It will review
common oral symptoms related to the disease and medications
to treat the disease, provide an overview of TN, review
anesthetic considerations, discuss treatment considerations in
patients on immunosuppressants/immunomodulators,
corticosteroids, and bisphosphonates, and provide suggestions
for treatment of patients in the more advanced stages of MS.
Oral Disease Prevention and Care of the
MS Patient
Dental clinicians should be in communication with the
patient’s other health care providers from the beginning of the
patient’s care. A thorough medical history should be obtained
from the patient or health care agent and confirmed with the
MS specialist. It should include the clinically active or
nonactive state and type of MS, a review of systems, a list of
medications the patient is currently on as well as an
understanding of the side effects, a record of past
bisphosphonate use, and recent blood workups (which will be
elaborated on in future sections).
Next, an oral hygiene and caries risk assessment should be
performed. A thorough discussion on prevention, dietary
counseling, and a review of patient goals and expectations
should be had with the patient and family members. Some
studies suggest that patients living with MS have a higher
incidence of tooth loss, silent infection, and caries.
2,4,5
Most
dental disease is preventable, and therefore, this does not need
to be the case. The biggest risk factors for dental disease are
challenges in motor coordination for proper oral hygiene and
difficulties with access to care. In one study, 48.5% of
individuals with MS reported their health as poor, and of
those, only 56% reported having seen their dentist in the last
6 months; of these, some reported difficulty in accessing the
building (21%) and the waiting room (11%), while only a few
(38%) reported suitable parking and less than half (48%)
suitable toilet facilities. 6 The optimal time to treat patients is
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when the disease is clinically inactive, when symptoms are
minimal. Even as the disease progresses, there are no
contraindications to treatment; however, modification to
treatment modalities should be considered. Dental
management should be adjusted over time to each person’s
needs (see Tables 21.1 and 21.2). Suggestions for treatment of
the patient with more advanced MS will be reviewed in the
last section of this chapter.
Table 21.1
Considerations in Prevention and Management of Patients With
Multiple Sclerosis (MS)
Physical challenges in
oral hygiene
Customized toothbrush handles from dental
acrylic or silicone impression putty to improve
grip
7,8
Use of electric toothbrush (Sonicare®, Oral B),
power flosser (AirFloss®, Waterpik®)
Recommend patient to sit down, rest arms on
commode while brushing if fatigued
Instruct family member or caretaker on
assistance with hygiene when needed
Caries risk prevention
Fluoride supplementation in the form of trays,
1.1% sodium fluoride (PreviDent®, Colgate)
paste or gel
Diet counseling including recommendations
for reduction of acidic/sugary beverages and
awareness of hidden sugars
Use of products with xylitol substitutes
(Spry®)
Frequent recalls (q3-4 mo)
Xerostomia
Sialagogues
Muscarinic acetylcholine agonists (pilocarpine
and cevimeline)
Postmeal rinses with 8 oz water and ½ tsp
baking soda
Smoking cessation
Saliva substitutes (Biotene Oral balance
Moisturizing Gel®, Xylimelts®)
Hypersalivation/inability
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to control saliva Portable Yankauer suction at home in the more
debilitated patient
Botox injections at the parotid gland
Increase incidence of
herpes simplex virus,
candidiasis, angular
cheilitis
Common findings related to
immunosuppression and xerostomia. Prescribe
proper antiviral or antifungal medication for
fungal or viral infections
Table 21.2
Considerations in Treatment and Improving Access to Care of Patients
With Multiple Sclerosis (MS)
Provide wheelchair accessibility and staff assistance from the entrance to the
operatories
Provide bathroom breaks before and during procedures for those with urinary
incontinence
Provide sources of transportation assistance
Schedule morning visits as fatigue tends to be more pronounced in the afternoon
Consider shorter appointments for more symptomatic patients and more frequent
recalls
Consider different levels of sedation for treatment depending on anxiety,
neurological symptoms, or severity of the disease
Careful use of isolation methods and adequate evacuation as respiratory muscle
and gag reflex impairment become more pronounced. Use a rubber dam for
proper isolation if patient can adequately breathe through the nose. Use a bite
block. Treat these patients in a semisitting position
Understand existing trigeminal neuralgia or facial anesthesia and avoid
triggering episode
Consider dental implants for fixed prosthesis or to improve function of
removable prosthesis
Use of resin-modified glass ionomers (RMGI) restorations and cements for
biocompatibility and fluoride-releasing properties
Infections in MS Exacerbation of
Symptoms
There is sufficient evidence that infection can add to the
underlying abnormal immunological response of these
patients, which can increase the risk of exacerbation of
symptoms.
9,10
No studies have been conducted on the
association between dental infections and relapse specifically;
however, the activation of the innate immune system by
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microbial products in MS patients has been proposed to be
linked to the induction of MS relapse. 11 Systemic infection
increases T-cell proliferation and proflammatory interleukins,
leading to higher levels of inflammatory response.
11,12
A
number of bacterial and viral strains have been suggested to
have a correlation on worsening some MS activity.
Staphylococcus aureus enterotoxin A, for example, has been
suggested to be one risk factor for exacerbations through
activation of disease modulating T-cells. 13 Evidence has also
demonstrated that upper respiratory infections have been
linked to subsequent relapses.
12,14
Relapses are a distinctive characteristic of MS, and although
they are usually followed by a period of clinical inactivity,
residual side effects cause persistent functional impairment,
impacting the quality of life of these individuals. Management
and reduction of potential causes associated with MS relapses
is important, as it may help to shorten and lessen the disability.
Furthermore, patients on steroids or disease-modifying drugs
may have a decreased ability to fight opportunistic infections
or dental infections. Oral-facial infections should be identified
and prevented early on. Patients with maxillary tooth and sinus
pain or ear pain of nondental origin should be referred for
evaluation if an upper respiratory infection is suspected.
Antibiotics, antivirals, and/or antifungals should be judiciously
prescribed as needed, and necessary treatment should be
carried out early on. Patients with any suspicion of infection
should be followed up with.
Multiple Sclerosis Treatment Medications
and Oral Health
Although there is no cure for MS, the focus of treatment is to
reduce the number of relapses and slow the disease process.
The most common medications are steroids for treatment of
acute attacks, disease-modifying therapies to suppress the
activity of the disease, and symptomatic therapy for MS side
effects, such as muscle relaxants, antidepressants, and
anticholinergics. It is important to be aware of drug
interactions when using medications in dentistry, and
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