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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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than one patient having an allergy to the influenza vaccine in
the Tysabri group.
A phase 4 open-label randomized study was done to evaluate
the effects of Tysabri treatment on the immune response to
vaccination in patients with relapsing MS. This study
measured memory antibody responses to neoantigen (keyhole
limpet hemocyanin) and analyzed the effects of Tysabri on
circulating lymphocyte subsets at 3 and 6 months of treatment.
No significant differences were noted between Tysabri-treated
and vaccines-only groups in the proportion of responders to
recall immunization with Td or primary immunization with
KLH, and all subjects had protective levels of Td antibodies.
Sleep Disorders in MS
Another common presenting complaint from a patient with
MS is problem with sleep, either due to difficulty falling
asleep or staying asleep. Poor sleep patterns can aggravate
daytime fatigue, which is often a common symptom for up to
90% of patients with MS at some point during their disease
course.30 It can also aggravate problems with poor cognition.
Insomnia, obstructive sleep apnea, and restless leg syndrome
need to be investigated because treatment can not only
improve restful sleep and decrease fatigue but also improve
overall quality of life.
Up to 40% of patients with MS may have insomnia.30 Many
symptoms such as spasticity, anxiety, depression, pain, and
overactive bladder can contribute to difficulty falling asleep.
Identification of these issues and treatment can help in
decreasing insomnia. Discussion with patient should be had
about improving sleep hygiene, maintaining a cool bedroom
temperature, and exercise except not close to bedtime. Patients
who are taking CNS stimulants, such as modafinil or
methylphenidate, have to be counseled not to take these close
to bedtime but should restrict use to the morning or early
afternoon at the latest. Use of antihistamines should be
avoided because of risk of psychomotor impairment and
daytime grogginess. Benzodiazepines or benzodiazepine
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agonists are preferred. Behavioral modification strategies,
meditation, and yoga can also be helpful.
Sleep apnea is often overlooked, but especially if a patient or
spouse is noting that snoring is present, frequent nighttime
awakenings occur, or daytime sleepiness is present, this should
be investigated. Overnight sleep study and referral to a sleep
specialist can help to diagnose this. Patients who have
brainstem dysfunction could be at an increased risk for this. If
this condition is diagnosed, positive airway pressure is usually
the preferred treatment. Restless leg syndrome, defined as
uncomfortable sensation or restlessness of the lower
extremities, usually present in the evening, helped with
movement, and worsened by rest can be seen in patients with
MS. Studies have shown that restless leg movements are three
times more common in patients with MS than in the general
population. Treatment should be individualized based on the
frequency and severity of symptoms.
Lymphedema
Lymphedema is the abnormal accumulation of interstitial fluid
resulting from injury, infection, or congenital deformities of
the lymphatic system. It is classified as primary lymphedema,
which is the presence of lymphedema without any inducing
factor, often a result of a congenital condition of the lymphatic
vessels, or secondary lymphedema, which occurs as the result
of a separate underlying condition or treatment. Common
causes of secondary lymphedema are cancer and cancer
treatment, infection, obesity, venous insufficiency, and
inflammatory disorders. The main cause of lymphedema in
conditions such as MS is reduction in the muscle movements
that usually enable the lymphatic fluid to flow properly. Often
there is greater lymphedema in the weaker extremity. Unlike
most other causes of lymphedema, in MS it is not caused by
venous insufficiency, or cardiac failure, but in patients who are
less ambulatory there should be a high index of suspicion for
deep vein thrombosis and cellulitis.31 Treating with diuretics is
usually not recommended. For mild cases of lymphedema,
compression socks and keeping legs elevated help. For more
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severe cases, lymphatic therapy and the use of compression
pumps are recommended.
Wellness and Coordination of Care
An important goal of MS treatment is to best maintain and
enhance the central nervous system reserve. What may seem
to be a common sense approach can make significant
difference. Cessation of tobacco use, increasing vitamin D
levels, optimizing body weight, regular exercise, healthy diet,
controlling comorbidities, and improving intellectual and
social stimulation and emotional well-being are measures that
need to be reinforced to patients and have them understand
their importance. A healthier lifestyle can help the CNS age
well and preserve the CNS reserve.
Because there has been an increased focus on alternative and
complementary therapies in MS, there is greater discussion
presently regarding integrative medicine. This refers to
integration of approved DMTs, complementary therapies, and
lifestyle medicine that emphasize overall wellness mindset,
with diet and exercise incorporated into what we consider
conventional medicine. Behavioral change often is necessary
for patients to adopt a healthier lifestyle. Of increased
importance is understanding the lifestyle of patients, what their
specific treatment goals are, and what might interfere with
adherence to treatment plan.
As discussed earlier in this chapter, the presence of
comorbidities decreased patients’ quality of life and affected
treatment adherence. Time spent in educating patients on the
importance of exercise and diet and their role in improving
overall MS disease management can produce long-term
positive ripple effects. Complementary therapies can include
acupuncture, yoga, tai chi, mindfulness, therapeutic massage,
reflexology, art and music therapy, magnetic therapy,32 and
hippotherapy.33 One study even showed benefits of cha cha
dancing in MS!34 Small positive steps should be encouraged
and reinforced. Discussion of being active versus inactive
should be stressed.
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As to diet, this is discussed in greater detail in another chapter.
In general, there is not one specific best diet for MS; however,
much research is ongoing studying the Mediterranean diet,
which emphasizes fruits, vegetables, whole grains, legumes,
and fish.35 Cannabis use in MS can play a role particularly for
pain and spasms.36 Certain states have legalized marijuana for
medicinal use; however, because it is not approved on the
federal level, patients may be at risk for federal offenses when
traveling from state to state. Bee venom was thought to be
possibly helpful for the treatment of MS; however, studies
show that there is no significant effect.37 Opiate antagonist
medications have also been in the discussion for the treatment
of MS, particularly naltrexone. Low-dose naltrexone has not
shown benefit in long-term disease progression; however,
some studies have shown benefit in decreasing fatigue.
38
In general, patients should be counseled to check with their
health care provider regarding any supplements because some
can be immune stimulating, such as echinacea, and are not
generally recommended. The most important supplement to
monitor is vitamin D, because not only can low vitamin D
levels can play a role in disease development but also
increased vitamin D levels can play a role in decreasing CNS
inflammatory activity in patients who already have MS.
Studies have shown benefit in achieving blood vitamin D
levels in the 60- to 80-ng/mL range.
36,39
Awareness of increased infection risks with certain DMTs,
possible drug-drug interactions, emphasis on wellness and
good health practices, and attention to treatment of
comorbidities can potentially lead to not only improved
overall health but also improvement in MS disease activity.
Collaboration between internists, family practitioners, nurse
practitioners, and physicians assistants with neurologists is key
to improved patient outcomes.
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C H A P T E R 7
Multiple Sclerosis in
Emergency Medicine
Richard I. Lappin
Introduction
Multiple sclerosis is an immune-mediated inflammatory
demyelinating disease of the central nervous system whose
cause and pathogenesis are still unclear. Both genetic and
environmental factors seem to influence susceptibility to the
disease. With an incidence of 2 to 10 cases per 100,000
persons per year (in the United States, Canada, and Europe),
MS is a relatively uncommon disease, but because it usually
begins early in life it is a major cause of disability in young
adults.
1
The classic lesion of MS is the plaque, seen in the white matter
of the brain or spinal cord. In the acute phase, plaques show a
combination of inflammatory cell infiltration, extensive
demyelination, and some degree of axonal damage. White
matter lesions are typically found in the periventricular region,
corpus callosum, centrum semiovale, deep white matter, and
basal ganglia. 2 More recently, histopathology and imaging
have shown that gray matter lesions are common even in early
MS and may be critical to the progression of disease. Gray
matter lesions can be found in the cerebral cortex, deep
structures such as the thalamus, the cerebellum, and the gray
matter of the spinal cord. They are difficult to detect without
specialized magnetic resonance imaging (MRI) sequences
such as double inversion recovery. Although they do show
demyelination, gray matter lesions are not marked by massive
inflammatory infiltration or evidence of blood-brain barrier
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(BBB) breakdown; the inflammatory cells in these lesions may
derive from the meninges or choroid plexus and enter from the
cerebrospinal fluid (CSF) via the pial surface or ventricles.
3
It is clear that MS lesions are often asymptomatic. Autopsy
studies show that some persons have central nervous system
(CNS) lesions consistent with MS and no clinical evidence of
disease. Patients presenting with what appears clinically to be
a first attack of demyelination (clinically isolated syndrome, or
CIS) are often found to have multiple old plaques on MRI
without any prior history of neurological disease. Repeat
imaging of patients in the relapsing phase of MS shows that
new lesions appear at a rate 5- to 10-fold greater than in
clinical relapses.
Advanced MS is also associated with diffuse atrophy of the
brain and spinal cord, which is closely correlated with
disability. The connection between the acute lesions of MS
and later atrophy is unclear.
Natural History of Multiple Sclerosis
The median age of onset of multiple sclerosis is approximately
30 years, although the disease can begin anywhere from early
childhood to the seventh decade of life. For approximately
85% of patients with MS, the disease will begin with a
relapsing-remitting pattern. The hallmark of relapsingremitting MS (RRMS) is the relapse (also called attack or
exacerbation), defined as an episode of neurological
dysfunction lasting at least 24 hours and not associated with
fever or infection. Attacks develop over a period of hours to
days and resolve over weeks to months. They are currently
believed to be episodes of acute demyelination. On average,
patients with RRMS will have a clinically apparent relapse
every 2 years; more frequent assessment of patients tends to
yield higher estimates of relapse rate. Relapses tend to be more
frequent early in the disease and wane over time. Each relapse
may have complete clinical resolution, or there may be
permanent sequelae. In the relapsing-remitting phase, there is
relatively little disease progression between acute relapses.
4-6
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Some clinical features at the very beginning of the disease, for
example, residual deficit after the first relapse and number of
relapses during the first 2 years, correlate with a shorter time
to reach disability milestones during the relapsing-remitting
phase. By contrast, relapses over the remainder of the
relapsing-remitting phase appear to have little effect on the
speed at which disability accumulates.
Most patients with RRMS will, after 10 to 20 years, gradually
transition to a secondary progressive phase, dominated by
steadily worsening disability with few or no relapses. By
9 years after disease onset, only half of patients will still have
relapses. The frequency of relapses and rate of accumulation
of disability during the relapsing-remitting phase vary
tremendously from patient to patient. However, once relapsing
patients reach an Extended Disability Status Scale (EDSS)
score of 3 or begin a progressive phase, they enter a period of
steady decline, which is similar from patient to patient and
only weakly influenced by the speed of the relapsing-remitting
phase.
7
About 15% of patients will present with primary-progressive
MS (PPMS), characterized by slowly worsening disability
from the onset of the disease. The distinction between RRMS
and PPMS is made exclusively by history; there are no
examination or imaging findings that distinguish the two
variants. The most common presentation of PPMS is a
gradually worsening spinal cord syndrome with spastic
paraparesis and no clear sensory level.
Pseudorelapses
MS symptoms can be worsened in the presence of infection or
other physiologic stress, a situation referred to as a
pseudorelapse.
3,4
Worsening of symptoms via increased body
temperature (Uthoff phenomenon) may underlie some of these
episodes. Classical pseudorelapses are exacerbations of
previous symptoms and typically include worsened
generalized fatigue and spasticity. In the emergency
department (ED), any patient with MS with worsened
symptoms should be screened for infection, especially of the
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