Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_2745_Библиотеки_им_академика_М_И_Перельмана
.pdf
Product Teriflunomide Fingolimod Dimethyl
Fumarate (DMF)
IFNβ-1a, IFNβ-1b,
PEG IFNβ-1a
Glatiramer Acetate
Monitoring
Before
starting:
CBC, LFT,
TB test,
blood
pressure
After
starting:
monthly
LFT × 6 mo,
periodic BP
monitoring
Monitor
ECG before
and for 6 h
after starting
first dose in
a setting that
can readily
manage
symptomatic
bradycardia
Others:
monitor
heart rate,
CBC,
pulmonary
function
test, liver
enzymes,
and BP
Before
starting:
CBC, LFTs
After
starting:
CBC after
6 mo, then
every 612 mo, and
as clinically
indicated.
Obtain
LFTs as
clinically
indicated
Consider
interrupting
treatment in
patients
with
lymphocyte
counts
<500,
persisting
more than
6 mo
Discontinue
treatment if
there is
clinically
significant
liver injury
CBC, LFTs
at 1, 3, 6 mo
Thyroid
function tests
No laboratory
monitoring
required
ALT, alanintransferase; BP, blood pressure; CBC, complete blood count; CNS, central nervous system; DHODH,
dehydroorotatedehydrogenase; ECG, electrocardiography; IFN, interferon; LFT, liver functional tests; MoA,
mechanism of action; MS, multiple sclerosis; PEG, polyethylene glycol; PML, progressive multifocal
leukoencephalopathy; TB, tuberculosis.
Bibliography
Noseworthy JH, Lucchinetti C, Rodriguez M, et al. Multiple sclerosis. N Engl J Med. 2000;343:938-952.
Giovannoni G, Butzkueven H, Dhib-Jalbut S, et al. Brain health: time matters in multiple sclerosis. Mult Scler Relat
Disord. 2016;9(suppl 1):S5-S48.
Arnason B, Berkovich R, Catania A, et al. Therapeutic mechanisms of action of adrenocorticotropic hormone (ACTH)
and other melanocortin peptides for the clinical management of patients with MS. Mult Scler. 2012. (in press).
Barnes D, Hughes RAC, Morris RW, et al. Randomised trial of oral and intravenous methylprednisolone in acute relapses
of multiple sclerosis. Lancet. 1997;349:902-906.
Barnes M, Bateman D, Cleland P, et al. Intravenous methylprednisolone for multiple sclerosis in relapse. J Neurol
Neurosurg Psychiatry. 1985;48:157-159.
Beck RW, Cleary PA, Anderson MM, et al. A randomized, controlled trial of corticosteroids in the treatment of acute
optic neuritis. N Engl J Med. 1992;9:581-588.
Berkovich R, Subhani D, Steinman L. Autoimmune comorbid conditions in multiple sclerosis. US Neurol, 2011;7(2):132-
138.
Berkovich R. Treatment of acute MS relapses. Neurotherapeutics. 2013;10(1):97-105.
Merkel B, Butzkueven H, Traboulsee AL, et al. Timing of high-efficacy therapy in relapsing–remitting multiple sclerosis:
a systematic review. Autoimmun Rev. 2017;16:658-665.
Giovannoni G, Southam E, Waubant E. Systematic review of disease-modifying therapies to assess unmet needs in
multiple sclerosis: tolerability and adherence. Mult Scler. 2012;18:932-946.
Comi G. Induction vs. escalating therapy in multiple sclerosis: practical implications. Neurol Sci. 2008;29(suppl 2):S253-
S255.
Fenu G, Lorefice L, Frau F, et al. Induction and escalation therapies in multiple sclerosis. Antiinflamm Antiallergy Agents
Med Chem. 2015;14:26-34.
https://t.me/medicina_free
Rush CA, MacLean HJ, Freedman MS. Aggressive multiple sclerosis: proposed definition and treatment algorithm. Nat
Rev Neurol. 2015;11:379-389.
Biogen Press Release on 2 March, 2018. Available at http://newsroom.biogen.com/press-release/autoimmune-
diseases/biogen%C2%A0and-abbvie-announce%C2%A0-voluntary%C2%A0worldwide-withdrawal-marketi. Last
accessed March 5, 2018.
Gajofatto A, Benedetti MD. Treatment strategies for multiple sclerosis: when to start, when to change, when to stop?
World J Clin Cases. 2015;3:545-555.
McGraw CA, Lublin FD. Interferon beta and glatiramer acetate therapy. Neurotherapeutics. 2013;10:2-18.
Filippini G, Del Giovane C, Clerico M, et al. Treatment with disease-modifying drugs for people with a first clinical
attack suggestive of multiple sclerosis. Cochrane Database Syst Rev. 2017;4:CD012200.
Metz LM, Li DKB, Traboulsee AL, et al. Trial of minocycline in a clinically isolated syndrome of multiple sclerosis. N
Engl J Med. 2017;376:2122-2133.
Miller AE, Wolinsky JS, Kappos L, et al. Oral teriflunomide for patients with a first clinical episode suggestive of
multiple sclerosis (TOPIC): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurol.
2014;13:977-986.
Burness CB, Deeks ED. Dimethyl fumarate: a review of its use in patients with relapsing–remitting multiple sclerosis.
CNS Drugs. 2014;28:373-387.
Schulze-Topphoff U, Varrin-Doyer M, Pekarek K, et al. Dimethyl fumarate treatment induces adaptive and innate
immune modulation independent of Nrf2. Proc Natl Acad Sci USA. 2016;113:4777-4782.
Fox RJ, Miller DH, Phillips JT, et al. Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis.
N Engl J Med. 2012;367:1087-1097.
Bar-Or A, Pachner A, Menguy-Vacheron F, et al. Teriflunomide and its mechanism of action in multiple sclerosis. Drugs.
2014;74:659-674.
Vermersch P, Czlonkowska A, Grimaldi LM, et al. Teriflunomide versus subcutaneous interferon beta-1a in patients with
relapsing multiple sclerosis: a randomised, controlled phase 3 trial. Mult Scler. 2014;20:705-716.
D’Amico E, Zanghi A, Leone C, et al. Treatment-related progressive multifocal leukoencephalopathy in multiple
sclerosis: a comprehensive review of current evidence and future needs. Drug Saf. 2016;39:1163-1174.
Gold R, Kappos L, Arnold DL, et al. Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N
Engl J Med. 2012;367:1098-1107.
Kappos L, De Stefano N, Freedman MS, et al. Inclusion of brain volume loss in a revised measure of ‘no evidence of
disease activity’ (NEDA-4) in relapsing–remitting multiple sclerosis. Mult Scler. 2016;22:1297-1305.
Matta AP, Nascimento OJ, Ferreira AC, et al. No evidence of disease activity in multiple sclerosis patients. Expert Rev
Neurother. 2016;16:1279-1284.
Nixon R, Bergvall N, Tomic D, et al. No evidence of disease activity: indirect comparisons of oral therapies for the
treatment of relapsing–remitting multiple sclerosis. Adv Ther. 2014;31:1134-1154.
Alroughani R, Deleu D, El Salem K, et al. A regional consensus recommendation on brain atrophy as an outcome
measure in multiple sclerosis. BMC Neurol. 2016;16:240.
Sormani MP, De Stefano N. Defining and scoring response to IFN-[beta] in multiple sclerosis. Nat Rev Neurol.
2013;9:504-512.
Belachew S, Phan-Ba R, Bartholome E, et al. Natalizumab induces a rapid improvement of disability status and
ambulation after failure of previous therapy in relapsing–remitting multiple sclerosis. Eur J Neurol. 2011;18:240-245.
Castillo-Trivino T, Mowry EM, Gajofatto A, et al. Switching multiple sclerosis patients with breakthrough disease to
second-line therapy. PLoS One. 2011;6:e16664.
Cohen JA, Coles AJ, Arnold DL, et al. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with
relapsing–remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet. 2012;380:1819-1828.
Cohen JA, Khatri B, Barkhof F, et al. Long-term (up to 4.5 years) treatment with fingolimod in multiple sclerosis: results
from the extension of the randomised TRANSFORMS study. J Neurol Neurosurg Psychiatry. 2016;87:468-475.
Hauser SL, Bar-Or A, Comi G, et al. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med.
2017;376:221-234.
Putzki N, Kollia K, Woods S, et al. Natalizumab is effective as second line therapy in the treatment of relapsing remitting
multiple sclerosis. Eur J Neurol. 2009;16:424-426.
Ziemssen T, De Stefano N, Pia Sormani M, et al. Optimizing therapy early in multiple sclerosis: an evidence-based view.
Mult Scler Relat Disord. 2015;4:460-469.
Polman CH, O’Connor PW, Havrdova E, et al. A randomized, placebo-controlled trial of natalizumab for relapsing
multiple sclerosis. N Engl J Med. 2006;354:899-910.
Kalincik T, Horakova D, Spelman T, et al. Switch to natalizumab versus fingolimod in active relapsing–remitting
multiple sclerosis. Ann Neurol. 2015;77:425-435.
O’Connor PW, Goodman A, Kappos L, et al. Disease activity return during natalizumab treatment interruption in patients
with multiple sclerosis. Neurology. 2011;76:1858-1865.
Giovannoni G, Marta M, Davis A, et al. Switching patients at high risk of PML from natalizumab to another disease-
modifying therapy. Pract Neurol. 2016;16:389-393.
https://t.me/medicina_free
Tuohy O, Costelloe L, Bjornson I, et al. Alemtuzumab treatment of multiple sclerosis: long-term safety and efficacy. J
Neurol Neurosurg Psychiatr. 2015;86:208-215.
Willis MD, Harding KE, Pickersgill TP, et al. Alemtuzumab for multiple sclerosis: long term follow-up in a multi-centre
cohort. Mult Scler. 2016;22:1215-1223.
Montalban X, Hauser SL, Kappos L, et al. Ocrelizumab versus placebo in primary progressive multiple sclerosis. N Engl
J Med. 2017;376:209-220.
Menge T, Dubey D, Warnke C, et al. Ocrelizumab for the treatment of relapsing–remitting multiple sclerosis. Expert Rev
Neurother. 2016;16:1131-1139.
Chen DR, Cohen PL. Living life without B cells: is repeated B-cell depletion a safe and effective long-term treatment
plan for rheumatoid arthritis? Int J Clin Rheumtol. 2012;7:159-166.
Berger JR. Classifying PML risk with disease modifying therapies. Mult Scler Relat Disord. 2017;12:59-63.
Giovannoni G, Comi G, Cook S, et al. A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis. N
Engl J Med. 2010;362:416-426.
Cook S, Vermersch P, Comi G, et al. Safety and tolerability of cladribine tablets in multiple sclerosis: the CLARITY
(CLAdRIbine Tablets treating multiple sclerosis orallY) study. Mult Scler. 2011;17:578-593.
Atkins HL, Bowman M, Allan D, et al. Immunoablation and autologous haemopoietic stem-cell transplantation for
aggressive multiple sclerosis: a multicentre single-group phase 2 trial. Lancet. 2016;388:576-585.
Lublin FD, Baier M, Cutter G. Effect of relapses on development of residual deficit in multiple sclerosis. Neurology.
2003;61(11):1528-1532.
https://t.me/medicina_free
C H A P T E R 3
Evaluation and Diagnosis of
the Multiple Sclerosis Patient
Hunter Vincent, Mary Ann Picone, Constantine J. Pella, Annette Okai
Introduction
Evaluating a patient with intermittent neurologic symptoms
can be a complex process with a myriad of differential
diagnosis and diagnostic algorithms. Often times, the
nonneurologist will overlook multiple sclerosis (MS) as a
differential diagnosis, because traditionally MS has been
viewed as a diagnosis of exclusion and other more common
etiologies need to be ruled out. Although the diagnosis of MS
is still uncommon, it is the most common neurologic disorder
of young adults in the United States, affecting nearly 1 million
people in the United States and 2.5 million globally, with the
median prevalence estimated at nearly 33 per 100,000 globally
as of 2013 and continuing to increase. 1 As the prevalence of
MS increases, it is important for the nonneurologist to have a
basic understanding of a neurologist’s perspective on the
evaluation and diagnosis of a patient with a high likelihood for
MS. When considering MS as a diagnosis, there are telltale
signs and symptoms that should stand out as more disease
specific for MS, involving symptom timeline, magnetic
resonance imaging (MRI) findings, physical examination
findings, and common laboratory or diagnostic tests, which
can help differentiate MS from other common disease mimics.
Understanding some of the subtleties and atypical disease
presentations can provide a nonneurologist with a valuable
skillset to provide an earlier diagnosis and treatment options.
Although this chapter is not intended to be a comprehensive
reference for physicians, it will surely provide an efficient and
https://t.me/medicina_free
effective framework for the evaluation and diagnosis of MS.
Let us first start by demonstrating a common clinical scenario
that a nonneurologist may encounter, to set the stage for more
detailed discussion about further workup and diagnosis.
Case Study
A 29-year-old woman who was in her usual state of good
health until 4 months ago began to notice some dragging of
her right leg after walking 2 miles. This was especially
noticed when she had been exercising and had increased
body temperature. Resting and cooling down would quickly
clear up her right leg weakness. She thought she might be
out of shape and did not seek any medical attention. Other
than some mild sense of fatigue, which she also attributed to
increased stress at work, she had no other symptoms.
Recently, she began to notice decreased sensation in the
right buttocks that persisted over 24 hours and then she
began to notice numbness in her right foot and leg, followed
a few days later with numbness in the left leg. She went to
an urgent care center where she was told she had a lower
back problem, probably a “pinched nerve,” and was given
anti-inflammatory medication.
She began to notice hesitancy with urination, and it became
more difficult for her to urinate. The numbness in her legs
worsened, and she had increased weakness in her right leg.
She then went to emergency department (ED), where she
needed to be catheterized because of severe urinary
retention. She had no cognitive deficits. On examination in
the ED, cranial nerve testing was normal. Motor testing
revealed 4+/5 weakness in the right lower extremity and T12
sensory level deficits. She also had a few beats of clonus at
bilateral ankles.
MRI of the brain was performed in the ED and revealed
greater than 10 scattered right and left periventricular ovoid
gadolinium-enhanced lesions perpendicular to the ventricles
and a demyelinating lesion in the T10-T12 levels of the
spinal cord, extending more to the right side of the cord.
https://t.me/medicina_free
Disease Phenotypes and Time Course
One of the many difficulties with diagnosing MS lies in the
fact that the disease presentation and neurologic symptoms are
largely variable between each clinical case, depending on the
location and severity of central nervous system (CNS)
demyelinating lesions. To date, there are four different clinical
phenotypes of MS, each presenting with a slightly different
disease course: clinically isolated syndrome (CIS), relapsing
remitting (RR), primary progressive (PP), and secondary
progressive (SP). To complicate the clinical picture further,
three of the phenotypes (RR, PP, SP) are technically classified
as either “active” or “not active” and “worsening” or “not
worsening” 2 (see Figure 3.1). Although proper disease
classification is not essential for initial diagnostic purposes, it
highlights the complexity of disease course and the burden that
is bestowed upon the diagnosing physician.
https://t.me/medicina_free
FIGURE 3.1 Multiple sclerosis disease phenotypes.
Reprinted with permission from Picone MA, Vincent H, BlitzShabbir K, West CY, Akinsanya J. Lower Extremity Signs and
Symptoms of Multiple Sclerosis. In: Positano RG , Borer JS ,
DiGiovanni CW , Trepal MJ , eds. Systemic Disease Manifestation
in the Foot, Ankle, and Lower Extremity. Philadelphia, PA: Wolters
Kluwer; 2017;284-300. Figure 25.1.
Clinically Isolated Syndrome
CIS is characterized as the first episode of neurologic
symptoms, lasting at least 24 hours, caused by an
inflammatory or demyelinating lesion in the CNS, but not
sufficient enough to satisfy the McDonald diagnostic criteria
for MS. The neurologic symptoms can be monofocal, affecting
https://t.me/medicina_free
only a single neurologic region such as the optic nerve in optic
neuritis (seen in approximately 20% of initial symptoms), or
multifocal, affecting multiple neurologic areas of the body.
3
The risk of CIS progressing to MS can vary depending on the
presence of a CNS-occupying lesion. 3 When CIS is present
with at least one demyelinating lesion in the CNS, the patient
has a 60% to 80% risk of a second neurologic episode and
being diagnosed with MS. 3 In patients with CIS without a
CNS lesion, the risk decreases to approximately 20%.
3
Preliminary clinical trials show that early treatment of patients
with CIS can decrease the risk of a second neurologic episode
and the conversion to “clinically definite MS.”
3
Relapsing Remitting MS
RR MS is the most common disease course, encompassing
approximately 85% of initial MS diagnosis. This MS disease
classification is defined by exacerbations of disease
symptoms, also known as relapses, followed by periods of
remission where no apparent clinical worsening or progression
of the disease occurs. However, changes can still be seen on
MRI examination. Neurologic symptoms often include
changes in vision, numbness, fatigue, spasticity, muscle
spasms, bowel/bladder problems, and cognitive difficulty.
3
However, the presentation of RR MS is oftentimes extremely
variable between patients and unique to each individual.
Patients may experience complete recovery of function and
resolution of symptoms following a relapse or only partial
recovery, leading to increased disability.
Primary Progressive MS
PP MS is a disease course characterized by worsening
neurologic status from the onset of diagnosis, usually without
relapses or remissions, affecting approximately 10% to 15% of
patients with MS. 3 PP MS usually affects men and women
equally and is often diagnosed later in life around the fourth or
fifth decade. 3 In addition, PP MS tends to present with an
increased number of spinal cord lesions with less
inflammatory cells, versus RR MS, which usually presents
https://t.me/medicina_free
with brain lesions (“plaques”) containing a larger number of
inflammatory cells. 3 It is common for patients with PP MS to
experience difficulty with walking and mobility, which can
potentially limit their ability to continue working.
3
Secondary Progressive MS
Secondary progressive MS generally presents initially as a
relapsing remitting disease course, in upward of 90% of cases,
3
but eventually transitions into a disease course defined by
progressive disability that is independent of relapse activity. A
majority of untreated patients with RR MS usually transition
to secondary progressive MS approximately 10 years after
diagnosis. 3 Although research is mixed, between 15% and
upward of 50% of patients with relapsing remitting disease
will advance to secondary progressive MS. 3 The onset of
secondary progressive MS is of large clinical significance,
because it has been shown to be the most important
determining factor for long-term prognosis with MS, and its
prevention is a crucial primary target for treatment.
3
Diagnostic Criteria
Traditionally, MS has been defined as a diagnosis of
exclusion. There is no single test or pathognomonic feature
that is specific for MS, and although the advent of MRI has
greatly improved ease of diagnosis, MS remains primarily a
clinically diagnosed disease. However, in recent years, more
concerted efforts have attempted to create more definitive
diagnostic criteria for the disease. Since 2001, the McDonald
criteria have been used as the gold standard for diagnostic
criteria in MS. Over the past 2 decades they have been revised
multiple times, most notably in 2010, with more minor
clarifications made in 2017 (see Table 3.1) to add specificity to
the 2010 criteria and improve diagnostic value.
4
According to the 2017 criteria (see Table 3.1), for patients
with a clinical course that begins with a neurologic attack, MS
can be definitively diagnosed in two separate scenarios
without the need of additional information. First, if a patient
https://t.me/medicina_free
suffers at least two neurologic attacks with objective clinical
evidence of at least two CNS lesions. Second, if a patient has
at least two clinical attacks, with evidence of one CNS lesion
and reasonable historical evidence of a prior attack involving a
distinct anatomical region. However, there are other clinical
presentations that do require other additional information to
make the diagnosis of MS. Before we explain these clinical
scenarios, there are specific terms that should first be
explained.
Table 3.1
2017 McDonald Criteria for Diagnosis of Multiple Sclerosis
Number
of
Clinical
Attacks
Number of Lesions With Objective
Clinical Evidence
Additional Data Needed for a
Diagnosis
≥2 ≥2 None
≥2 1 (also containing definite
historical evidence of a previous
attack due to a lesion in a distinct
anatomical location)
None
≥2 1 Attacks are DIS showing a
different CNS site or by MRI
scanning
1 ≥2 Attacks are DIT with additional
attacks, MRI scanning, or
presence of CSF-specific
oligoclonal bands
1 1 Attacks are DIS showing a
different CNS site or by MRI
scanning
And
Attacks are DIT with additional
attacks, MRI scanning, or
presence of CSF specific
oligoclonal bands
Adapted from Thompson AJ, Banwell BL, Barkhof F, et al. Diagnosis of multiple
sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol.
2018;17(2):162-173. Copyright © 2017 Elsevier. With permission. CNS, central
nervous system; CSF, cerebrospinal fluid; DIS, disseminated in space; DIT,
disseminated in time; MRI, magnetic resonance imaging.
Disseminated in Space (DIS): Although there is still some
debate, DIS refers to the development of lesions in distinct
anatomical locations within the CNS, indicating a multifocal
CNS process. It can be demonstrated by one or more T2hyperintense lesions that are characteristic of MS in two or
https://t.me/medicina_free
Соседние файлы в папке Библиотека им академика М.И. Перельмана