Biblioteca del NCBI. Un servicio de la Biblioteca Nacional de Medicina, Institutos Nacionales de Salud.
StatPearls [Internet]. Isla del Tesoro (FL): StatPearls Publishing; 2025 enero-.
Esclerosis múltiple
Dawood Tafti ; Moavia Ehsan ; Kathryn L. Xixis .
Información y afiliaciones del autor
Última actualización: 20 de marzo de 2024 .
Actividad de Educación Continua
La esclerosis múltiple es una enfermedad autoinmune crónica que afecta al sistema nervioso
central y se caracteriza por inflamación, desmielinización, gliosis y pérdida neuronal. Esta
afección se manifiesta con una amplia gama de síntomas neurológicos, como visión borrosa,
entumecimiento y hormigueo, debilidad focal, disfunción vesical e intestinal, y deterioro
cognitivo. La esclerosis múltiple presenta diversas evoluciones, incluyendo la recurrente-
remitente, la progresiva primaria y la progresiva secundaria. El diagnóstico precoz, generalmente
basado en episodios separados en el tiempo y el espacio, facilita el inicio inmediato de una
terapia modificadora de la enfermedad, destinada a reducir las recaídas y la discapacidad a largo
plazo, lo cual es crucial para un diagnóstico preciso de la esclerosis múltiple.
Los objetivos del tratamiento incluyen la disminución de las recaídas y la actividad de las
resonancias magnéticas, a la vez que se minimiza la discapacidad permanente y se abordan
diversas preocupaciones de los pacientes, como la disfunción vesical e intestinal, la depresión, el
deterioro cognitivo, la fatiga, la disfunción sexual, los trastornos del sueño y el vértigo. El
manejo eficaz de la esclerosis múltiple requiere un enfoque interdisciplinario y diversas opciones
de tratamiento, incluyendo terapias modificadoras de la enfermedad como el acetato de
glatiramer, el dimetilfumarato, el fingolimod, los preparados de interferón beta, el natalizumab y
la mitoxantrona. Esta actividad enfatiza el papel crucial de los profesionales de la salud
interprofesionales para facilitar la intervención temprana y lograr resultados óptimos en los
pacientes, debido al impacto de la enfermedad en múltiples sistemas y la reducción de la
esperanza de vida.
Objetivos:
Identificar signos y síntomas tempranos de la esclerosis múltiple en varios dominios
neurológicos.
Evaluar a los pacientes con riesgo de padecer esclerosis múltiple o que presenten síntomas
sugestivos mediante pruebas diagnósticas apropiadas, como resonancia magnética,
potenciales evocados y análisis del líquido cefalorraquídeo.
Seleccionar tratamientos sintomáticos adecuados para los síntomas relacionados con la
esclerosis múltiple, como espasticidad, fatiga, dolor y disfunción de la vejiga.
Colaborar con otros proveedores de atención médica para abordar comorbilidades, como
depresión, deterioro cognitivo y factores de riesgo cardiovascular, en pacientes con
esclerosis múltiple.
Acceda gratuitamente a preguntas de opción múltiple sobre este tema.
Introducción
La esclerosis múltiple es una enfermedad autoinmune crónica que afecta al sistema nervioso
central (SNC) y se caracteriza por inflamación, desmielinización, gliosis y pérdida neuronal. [1]
Esta afección se manifiesta con una amplia gama de síntomas neurológicos, como deterioro
visual, entumecimiento y hormigueo, debilidad focal, disfunción vesical e intestinal y deterioro
cognitivo.
Patológicamente, el infiltrado linfocítico perivascular y los macrófagos provocan la degradación
de las vainas de mielina que rodean las neuronas, lo que causa síntomas que varían según la
localización de la lesión. Los síntomas clínicos, caracterizados por recaídas agudas, suelen
aparecer primero en adultos jóvenes, seguidos de una evolución gradualmente progresiva que
conduce a una discapacidad permanente en un plazo de 10 a 15 años. [2]
La esclerosis múltiple presenta diversos cursos de enfermedad y se clasifica en siete categorías,
como se describe a continuación.
Remitente-recidivante (RR): este inicio se observa en el 70% al 80% de los pacientes con
esclerosis múltiple y se caracteriza por la presentación neurológica mencionada a
continuación.
Síntomas neurológicos nuevos o recurrentes compatibles con esclerosis múltiple
Síntomas que duran entre 24 y 48 horas.
Los síntomas se desarrollan a lo largo de días o semanas.
Primaria progresiva (PP): Este curso se presenta en el 15% al 20% de los pacientes y
muestra un deterioro gradual desde el inicio sin recaídas.
Secundaria progresiva (SP): Tras un curso inicial con recaídas y remisiones, este curso se
caracteriza por un deterioro neurológico más gradual. Pueden presentarse recaídas
superpuestas, pero no son obligatorias.
Recidivante progresiva (PR): este curso implica un deterioro gradual con recaídas
superpuestas y se observa en el 5% de los pacientes.
Además, a veces se consideran las siguientes tres categorías dentro del espectro de la esclerosis
múltiple:
Síndrome clínicamente aislado: a menudo se clasifica como un episodio único de
desmielinización inflamatoria del SNC.
Fulminante: Se caracteriza por una esclerosis múltiple grave con múltiples recaídas y
progresión rápida hacia la discapacidad.
Benigno: se caracteriza por una evolución general de discapacidad leve con raras recaídas.
Al hablar de esclerosis múltiple, los médicos suelen centrarse en el curso recurrente-remitente
debido a su alta prevalencia entre los pacientes afectados. Las recaídas en la esclerosis múltiple
recurrente-remitente suelen mostrar una recuperación parcial o completa en semanas o meses, a
veces sin tratamiento. Sin embargo, los síntomas residuales de estas recaídas, sin una
recuperación completa, pueden acumularse con el tiempo y contribuir a la discapacidad general.
El diagnóstico de esclerosis múltiple recurrente-remitente generalmente requiere evidencia de al
menos dos eventos inflamatorios del SNC. Aunque existen diversos criterios diagnósticos para la
esclerosis múltiple, el principio general para diagnosticar el curso recurrente-remitente consiste
en establecer episodios separados en el tiempo y el espacio. [3]
Esto implica que los episodios deben estar separados temporalmente y afectar distintas
localizaciones dentro del SNC. Un diagnóstico temprano de esclerosis múltiple permite el inicio
oportuno de una terapia modificadora de la enfermedad, lo que resulta en un manejo eficaz. [1]
Los objetivos del tratamiento incluyen la disminución de las recaídas y la actividad de la
resonancia magnética (RM), a la vez que se minimiza la discapacidad permanente y se abordan
diversas preocupaciones del paciente, como la disfunción vesical e intestinal, la depresión, el
deterioro cognitivo, la fatiga, la disfunción sexual, los trastornos del sueño y el vértigo.
Etiología
Aunque se desconoce la etiología exacta de la esclerosis múltiple, los factores implicados en la
patogénesis se agrupan en tres categorías generales: factores inmunes, factores ambientales y
asociaciones genéticas.
La disinmunidad con un ataque autoinmune al SNC es la principal hipótesis etiológica de la
esclerosis múltiple. El mecanismo "de afuera hacia adentro" postulado involucra a los linfocitos
T proinflamatorios CD4+, entre otros mecanismos propuestos. [4] Los investigadores plantean la
hipótesis de que un antígeno desconocido desencadena y activa los linfocitos Th1 y Th17, lo que
lleva a su adhesión al endotelio del SNC, cruza la barrera hematoencefálica y, posteriormente,
causa un ataque inmunitario por reactividad cruzada. Por el contrario, la hipótesis "de adentro
hacia afuera" sugiere una anomalía intrínseca del SNC que desencadena y resulta en daño tisular
de mediación inflamatoria. [4]
Los factores ambientales, como los gradientes latitudinales observados en diversos países, se han
estudiado exhaustivamente. [5] La deficiencia de vitamina D se ha considerado una posible
etiología de la predisposición observada en poblaciones de latitudes altas a la esclerosis múltiple.
[6] Ciertas infecciones, como el virus de Epstein-Barr, también pueden contribuir a la
enfermedad. [7] Son evidentes las interacciones complejas entre diversos factores ambientales y
la genética del paciente, y la investigación en curso busca comprender estas vías de forma más
exhaustiva.
Los pacientes con familiares biológicos con esclerosis múltiple tienen un mayor riesgo de
desarrollar la enfermedad. [8] Tener un familiar de primer grado con esclerosis múltiple se asocia
con un riesgo del 2% al 4% de desarrollar esclerosis múltiple, en comparación con el 0,1% en la
población general. [9] Las tasas de concordancia son mayores en gemelos monocigóticos (20% a
30%) que en gemelos dicigóticos (5%). [10] Existe una concordancia del 2% entre padres e
hijos, lo que sigue siendo un riesgo entre 10 y 20 veces mayor que en la población general. [11]
El alelo del antígeno leucocitario humano (HLA) DRB1*1501 se correlaciona fuertemente con la
esclerosis múltiple y es uno de los alelos más estudiados en relación con el vínculo con la
esclerosis múltiple. [12] No se observa una forma mendeliana definida de ocurrencia genética, y
las implicaciones apuntan a numerosos genes. [13]
Los polimorfismos en varios genes pueden estar asociados con un riesgo ligeramente mayor de
esclerosis múltiple, incluidos los siguientes: [14]
Genes relacionados con la inmunidad: HLA-DR , IL2RA , IL4 , IL6 , IL12B , IL17R ,
IRF5 , CD24 , CD58 y EVI5
Metabolismo de la vitamina D: VDR y CYP27B1
Ciertos genes en el ADN mitocondrial
Fibrinólisis: PAI-1
Función y reparación del SNC: ApoE y DPP6
Epidemiología
La esclerosis múltiple es la enfermedad desmielinizante inflamatoria inmunomediada más común
del SNC. Esta afección afecta aproximadamente a 400.000 personas en Estados Unidos y a 2,5
millones en todo el mundo. [15] La enfermedad es tres veces más común en mujeres que en
hombres. [15] Aunque suele aparecer en personas de entre 20 y 40 años, la esclerosis múltiple
puede presentarse a cualquier edad, siendo la edad media de aparición de 25 a 29 años para la
esclerosis múltiple recurrente-remitente y de 39 a 41 años para la esclerosis múltiple primaria
progresiva. [16] Casi el 10 % de los casos se presentan antes de los 18 años. [17] La prevalencia
general se estima en 1 por 1.000 en poblaciones de ascendencia europea. [18]
Less is known about the prevalence of multiple sclerosis in non-European populations, with most
data indicating lower prevalence in individuals of East Asian and African descent.[19] However,
recent studies have observed a higher prevalence in African-American populations, similar to
those with European ancestry.[19] Multiple sclerosis demonstrates a prevalence gradient based
on latitude, with higher prevalence in northern latitudes of Europe and North America.
Additionally, observations have noted variable genetic susceptibility factors among different
human subpopulations, apart from latitude, suggesting poorly understood genetic factors
interacting with environmental influences.
Several studies have highlighted that populations migrating to regions with higher multiple
sclerosis prevalence during childhood also adopt a higher risk of acquiring multiple sclerosis.[20]
However, other studies have raised doubts about this observation.[21] Neither genetic nor
external risk factors can solely account for the epidemiological patterns seen in multiple
sclerosis. Notably, multiple sclerosis stands as the leading cause of permanent disability among
young adults.[16] One study reported an incidence rate of pediatric-acquired multiple sclerosis at
0.51 per 100,000 person-years.[9]
Pathophysiology
The pathophysiology of multiple sclerosis primarily affects the CNS and involves various areas
such as the cortical gray matter, periventricular and juxtacortical white matter, optic nerves,
spinal cord, cerebellum, and meninges.
The 2 fundamental processes that constitute general pathological processes observed in
multiple sclerosis patients include:
Focal inflammation results in macroscopic plaques and injury to the blood-brain barrier.
Neurodegeneration involves microscopic damage to various components of the CNS, such
as axons, neurons, and synapses.
Together, these 2 primary processes result in macroscopic and microscopic injury. Lesions, called
plaques, occur in waves throughout the disease course and result from focal inflammation.
Multiple sclerosis plaques predominantly center around small veins and venules, displaying
sharp margins. The chief components of plaque pathology include myelin loss, edema, and
axonal injury. During active plaque inflammation, disruption of the blood-brain barrier
corresponds to enhancement observed on MRI scans. As the inflammatory process subsides over
time, it leads to the formation of an astrocytic scar (see Image. Perivascular Plaques in Multiple
Sclerosis as seen in MRI).
Microscopically, multiple sclerosis lesions show mononuclear infiltrates with perivenular cuffing
and infiltration surrounding the white matter. Innate immune cells such as monocytes and
macrophages stimulate T-cell migration across the blood-brain barrier, resulting in blood-brain
barrier injury and systemic immune cell infiltration. Microglia, the primary antigen-presenting
cells of the primary CNS, often precede cell entry. This CNS injury triggers cytotoxic activities
in microglia, leading to the release of nitric oxide and other superoxide radicals. Inflamed areas
with blood-brain barrier breakdown are visible on MRI as gadolinium-enhancing lesions.
Recently, a greater understanding of the critical role of B cells and antibody production has been
recognized in the pathogenesis of multiple sclerosis.[22] B-cell follicles in the meninges of
multiple sclerosis patients have been noted, and they are associated with early-onset multiple
sclerosis.[23] The pathological events ultimately lead to demyelination, neuroaxonal
degeneration, loss of synapses, dying-back oligodendrogliopathy, tissue injury, and astrogliosis.
Histopathology
Histologically, multiple sclerosis plaques are primarily characterized by inflammation and
myelin breakdown.[24] Additional features include neurodegeneration and oligodendrocyte
injury. The common histopathological stains used to detect multiple sclerosis, with adjunct
immunohistochemistry assisting in diagnosis, include hematoxylin and eosin staining, myelin
stains such as Luxol fast blue, monocyte and macrophage markers such as CD68, and axonal and
astrocyte stains.
Active plaques exhibit varying degrees of the following features:
Extensive macrophage infiltration
Myelin debris often found within macrophages
Presence of major myelin protein, notably in late active plaques
Perivascular inflammatory infiltrates
Presence of lymphocytes, particularly CD8-positive cytotoxic T cells
Plump-shaped and mitotic astrocytes
Variable degrees of oligodendrocyte injury
Activated microglia, particularly evident in the peri-plaque white matter zone
Chronic plaques are known for their circumscribed demyelinated lesions, and they occur more
frequently and exhibit the following features:[24]
Hypocellularity and demyelination
Macrophages laden with myelin
Relatively decreased perivascular inflammation compared to active plaques
Resolving edema
In remyelinated plaques, thinly myelinated axons and axons with newly formed myelin
sheaths are apparent.
Presence of oligodendrocyte precursor cells, typically seen in remyelinated plaques
History and Physical
Multiple sclerosis presents with a broad range of symptoms reflective of the multifocal lesions of
the CNS. The severity and diversity of symptoms are influenced by the burden, location, and
extent of tissue injury. Interestingly, symptoms may not always align with MRI evidence of
active plaques due to the involvement of repair mechanisms and neural plasticity in tissue injury
and recovery processes.
Typical clinical manifestations noted in patient history include:
Vision symptoms such as vision loss (either monocular or homonymous), double vision,
symptoms relating to optic neuritis, and pain with eye movement
Vestibular symptoms such as vertigo and gait imbalance
Bulbar dysfunction, which manifests as dysarthria and dysphagia
Motor symptoms such as weakness (hemiparesis, monoparesis, or paraparesis), tremors,
spasticity, and fatigue [25]
Sensory symptoms such as loss of sensation, paresthesias, dysesthesias, and a band-like
sensation around the chest or abdomen
Urinary and bowel symptoms ranging from incontinence, retention, urgency, constipation,
diarrhea, and reflux
Cognitive symptoms such as memory impairment, executive function impairment, and
difficulty concentrating
Psychiatric symptoms such as depression and anxiety
Brainstem symptoms such as facial muscle weakness and/or reduced facial
sensations, diplopia, oscillopsia (jerking sensation in the visual field)
Features considered atypical for multiple sclerosis include seizures, steady progression of
symptoms, deficits developing rapidly within minutes, onset before age 10 or after 50, rigidity or
sustained dystonia, cortical deficits such as apraxia, alexia, aphasia, or neglect, and early onset of
dementia.
The relapsing-remitting course of multiple sclerosis, observed in a majority of patients, is
characterized by exacerbation and relapses of neurological symptoms, with stability between
episodes.[26] The following features generally characterize the relapsing-remitting course of
multiple sclerosis:
New or recurrent neurological symptoms
Symptoms developing over days and weeks
Symptoms lasting between 24 and 48 hours
Symptoms from relapses frequently resolve. However, over time, residual symptoms relating to
episodes of exacerbation accrue. This accrual of symptoms, generally after 10 to 15 years, results
in long-term disability over time. Neurological manifestations are heterogeneous in severity and
degree of recovery. The secondary progressive course is often noted in patients with relapsing-
remitting after 10 to 15 years of onset and is characterized by a more gradual worsening of
symptoms with continued progression with or without superimposed relapses.[27]
A small subset of patients experience a progressive worsening of disability from the disease's
onset, known as the primary progressive course of multiple sclerosis. Clinical manifestations in
this course commonly include myelopathy, cognitive symptoms, and visual impairments. Diffuse
and chronic symptoms may arise from global brain atrophy and widespread cortical
demyelination.
The physical examination aligns with evaluating the patient's illness history and includes the
aspects mentioned below.
HEENT:
Assessment for optic neuritis, which typically presents as subacute monocular central
vision loss, along with pain upon eye movement (see Image. Optic Neuritis as an Indicator
of Multiple Sclerosis)
Observation of difficulty in adducting during lateral gaze, indicating internuclear
ophthalmoplegia
Other conditions, such as nystagmus, diplopia, hearing loss, and facial pain
Neuromuscular/neurological:
Partial transverse myelitis is typically unilateral or bilateral and is characterized by sensory
disturbances
Brainstem symptoms often include diplopia, dysphagia, dysarthria, and ataxia
The Lhermitte sign is often described as a shock-like sensation with neck flexion
Hyperreflexia, tremors, muscle spasms, and weakness
Genitourinary:
Urinary incontinence/retention with an assessment of residual bladder volume [28]
Erectile dysfunction with consideration of a nocturnal penile tumescence stamp test if
indicated
Isolated syndromes:
Isolated syndromes may present as:
Radiographically isolated syndrome: MRI brain lesions that are characteristic
of multiple sclerosis but are found in patients, usually incidentally, but they do not have
any symptoms of multiple sclerosis.
Clinically isolated syndrome: Isolated symptom that may not fulfill diagnostic criteria
for multiple sclerosis but can lead to clinically definite multiple sclerosis.
If multiple sclerosis is suspected but the patient does not present with typical symptoms, the
symptoms mentioned below should prompt further inquiry.[29]
Seizures
Sleep disorders, including obstructive sleep apnea, nocturia, insomnia, and restless legs
Transient (paroxysmal) neurological events, which typically last for seconds and occur
with frequencies ranging from hundreds of times per day to only occasionally, may
include:
Abnormal or unexplained sensation spreading across the body
Brainstem symptoms such as blurred vision, diplopia, dysarthria, and vertigo
Motor symptoms such as transient inhibition of motor function, tonic spasms, and
ataxia
Gustatory symptoms such as taste hallucination and altered taste
Hypothermia or hyperthermia (very rarely)
Pulfrich phenomenon (based on a mismatch of visual acuity between eyes)
Objects moving in a straight line appear to be in an elliptical orbit
May present with difficulty crossing roads, pouring liquids, playing ball sports, or
feeling cars swerving in direction while driving.
The sense of uselessness or loss of function in hand (known as "useless hand of
Oppenheim")
The Lhermitte phenomenon, occurring with less commonly observed triggers, such as limb
movements, neck extension, or coughing [30]
Red Flags for Alternative Diagnoses
Red flags that should alert the clinician to the possibility of other diagnoses include the
following:
Hyperacute presentation (maximal deficit in minutes to hours)
Progressive ataxia or cognitive dysfunction
Family history of any other neurological disease
Encephalopathy
Short-lasting symptoms (minutes to hours)
Rapidly progressive disease
Failure to remit
Leptomeningeal disease
Progressive ataxia
Cognitive dysfunction
Complete or fluctuating ophthalmoplegia
Headache and/or meningismus
Multiple cranial neuropathies or hearing loss
Symptoms of systemic disease such as night sweats, weight loss, and fever
Nonspecific neurological examination findings and/or neurological symptoms not easily
localized to the CNS (such as isolated fatigue)
Evaluation
Pathognomonic tests do not exist to diagnose multiple sclerosis. Diagnosis is established by
considering the patient's history and physical examination, along with MRI findings, evoked
potentials, and cerebrospinal fluid (CSF) or blood studies, while also excluding other causes of
the patient's symptoms. Clinically, a diagnosis of multiple sclerosis is supported by evidence of
one or more relapses, which can be confirmed through objective clinical evidence of one or more
lesions or objective clinical evidence of one lesion with reliable historical evidence of a prior
relapse.
Dissemination in space (DIS) and dissemination in time (DIT) are 2 key criteria for accurately
diagnosing multiple sclerosis. DIS is assessed by integrating information from the patient's
history and physical examination to determine the location of CNS involvement. MRI and
evoked potentials also have vital roles in establishing DIS. DIT is established by charting the
disease course with a thorough history and documenting the presence of multiple exacerbations
over time. The 2010 McDonald criteria determined that new lesions can demonstrate DIT on a
follow-up MRI compared to a baseline scan.[31]
DIS is established by observing at least a T2 lesion in 2 of the 4 following CNS sites—spinal
cord, infratentorial, juxtacortical, and periventricular regions. Revisions in the 2017 McDonald
criteria increased the sensitivity of diagnosis by introducing oligoclonal bands in the CSF
analysis as a marker for establishing DIT. Symptomatic lesions were also included to establish
DIT and DIS, and cortical lesions were used to demonstrate DIS.[32]
Evoked potentials help demonstrate slowed conduction indicative of subclinical involvement.
These findings are often asymmetric. MRI, CSF, and blood studies are essential in ruling out
other etiologies. When possible, all patients should undergo an MRI. Additionally, specific blood
studies such as complete blood count (CBC), thyroid-stimulating hormone (TSH), vitamin B12
levels, erythrocyte sedimentation rate (ESR), and antinuclear antibody (ANA) testing should be
performed as part of the diagnostic workup.
The main characteristics of multiple sclerosis lesions on brain MRI can be outlined as follows:
Lesions are T2 hyperintense and T1 isointense or hypointense, also known as black holes
(see Image. Sagittal FLAIR MRI Brain Image Demonstrating Linear Hyperintense
Lesions).
Lesions are typically oval or patchy.
A high predilection for periventricular white matter.
Lesions are oriented perpendicular to the ependymal surface, known as Dawson fingers
(see Image. Sagittal FLAIR Sequence Demonstrating a Hyperintense Lesion on MRI).
Active lesions often exhibit gadolinium enhancement, presenting as diffuse or rim
enhancement.
Thinning of the corpus callosum and parenchymal atrophy (see Image. Axial FLAIR
Sequence Demonstrating an Advanced Lesion Burden on MRI).
The disappearance of a black hole is most likely due to the resolution of edema and
remyelination.[33]
Spinal cord lesions typically exhibit the following MRI characteristics:
Typically located in the cervical or thoracic cord, often in the dorsolateral region.
Little or no cord swelling observed.
Lesions are focal, with clearly circumscribed and delineation on T2-weighted sequences.
Size ranges from 3 mm to less than 2 vertebral segments in length.
Unequivocal hyperintensity on T2-weighted sequences visible in 2 planes (eg, sagittal and
axial)
The classic abnormal CSF findings in multiple sclerosis typically include elevated protein and
myelin basic protein levels, occasional leukocytes (mainly mononuclear cells), and increased
levels of total immunoglobulin G (IgG), free kappa light chains, and oligoclonal bands.[34]
When clinical, imaging, or laboratory features are atypical of multiple sclerosis, patients are
tested for aquaporin-4 (AQP4) IgG serum autoantibody and the myelin oligodendrocyte
glycoprotein IgG autoantibody (MOG-IgG).
Table
Table. Diagnostic Tests for Multiple Sclerosis.
Table reference is [34].
Treatment / Management
Glatiramer acetate, dimethyl fumarate, fingolimod, interferon-beta preparations, natalizumab,
and mitoxantrone are some of the primary disease-modifying therapies. Immediate treatment
initiation upon diagnosis is crucial for multiple sclerosis. Short-term goals focus on decreasing
MRI lesion activity, while long-term goals aim to prevent secondary progressive multiple
sclerosis. Post-treatment challenges include ensuring patient compliance and monitoring for drug
toxicity.
In the realm of treatment and management for multiple sclerosis, several disease-modifying
therapies, as mentioned below, offer various mechanisms to address the underlying pathology.
Glatiramer acetate: This is a synthetic polypeptide mixture that may act as a ligand for major
histocompatibility complex molecules, limiting their activation and promoting regulatory cell
induction. This drug may also have neuroprotective and repair mechanisms.[35] Glatiramer
acetate is administered subcutaneously and is generally well-tolerated; however, this drug is
ineffective for progressive forms of multiple sclerosis.
Interferon-beta preparations: These preparations act through multiple mechanisms, including
modulation of T- and B-cell function, cytokine expression alteration, potential role in blood-brain
barrier recovery, and reduction in matrix metalloproteinase expression. The administration is
subcutaneously or intramuscularly, and they may cause flu-like symptoms and possibly briefly
worsen patients' neurological symptoms.
Natalizumab: This drug is an intravenously (IV) administered humanized monoclonal antibody
that blocks leukocyte adhesion to vascular endothelial cells, thereby inhibiting leukocyte
migration into the CNS. Although generally well tolerated, natalizumab may cause mild
headaches, and flushing may occur during IV administration.
Mitoxantrone: This is an IV-administered chemotherapeutic agent used to treat multiple
sclerosis due to its effects on DNA repair and RNA synthesis. A possible effect on cellular and
humoral immunity may represent the therapy mechanism for multiple sclerosis.[36] However, its
use is limited due to the various adverse effects that have been documented, including
amenorrhea and alopecia.
Fingolimod: This is an orally administered drug with immunomodulatory effects, possibly
relating to the inhibition of T-cell migration. However, possible adverse effects include
lymphopenia, bradycardia, and hepatotoxicity, thereby necessitating careful monitoring.
Patients with secondary progressive, progressive-relapsing, and primary progressive multiple
sclerosis primarily experience neurodegenerative processes. Due to this, disease-modifying
therapies show varying effectiveness, ranging from possible benefits to limited impact on disease
progression. Typically, younger patients with a shorter duration of progression tend to benefit
more from these therapies.
Guiding Principles for Acute Relapse Management
Several principles guide the treatment of acute relapses in multiple sclerosis, including:
Addressing possible underlying processes that could have triggered a relapse, such as an
infection or metabolic derangement
Providing symptomatic treatment based on specific neurological symptoms
Administering a short course of corticosteroids to assist in recovery
Implementing rehabilitation programs involving physical and occupational therapy for
comprehensive management
Women of childbearing age should avoid certain medications due to their potential risks, as listed
below.
Teratogens: Teriflunomide, cladribine, siponimod, fingolimod, and ozanimod
Drugs associated with a higher risk of rebound symptoms upon discontinuation:
Fingolimod, siponimod, natalizumab, and ozanimod
Treatment of Acute Exacerbation of Multiple Sclerosis
Neurological symptoms may include increased disability, impairments in strength, cerebellar
function, vision, or significant sensory disturbances.
IV or oral steroids may be prescribed by a physician, as described below, depending on a
patient's conditions and symptoms.
IV methylprednisolone: This can be administered as a 3- to 7-day course at 500 to
1000 mg daily, optionally followed by a short prednisone taper.[37]
Oral prednisone: This can be administered at a dosage of 1250 mg/d of prednisone,
with/without a short taper, and is an alternative to 3 to 7 days of oral
methylprednisolone administered at 1000 mg/d.
Plasma exchange (PLEX) is recommended if a poor glucocorticoid response occurs.[38]
PLEX is administered daily or every other day for a total of 3 to 7 treatments.
Differential Diagnosis
The differential diagnosis of multiple sclerosis is extensive and can be categorized into 7
categories, as listed below.
Other demyelinating or inflammatory CNS syndromes:
Optic neuritis
Marburg disease
Acute disseminated encephalomyelitis
Devic neuromyelitis optical
Susac syndrome [39]
Primary cerebral vasculitis and partial transverse myelitis
Chronic lymphocytic inflammation with pontine perivascular enhancement
responsive to steroids (CLIPPERS), a rare form of encephalomyelitis typically
affecting the spinal cord, cerebellum, and brainstem [40]
General inflammatory and autoimmune syndromes:
Systemic lupus erythematosus
Wegener granulomatosis
Sarcoidosis
Antiphospholipid antibody syndrome
Behcet syndrome
Sjögren syndrome
Infectious etiologies:
Lyme disease
Syphilis
HIV
Herpes viruses
Vascular etiologies
Migraine headaches
Dural arteriovenous fistula
Small vessel ischemia
Ischemic optic neuropathy (arteritic and nonarteritic)
Vascular malformations and emboli
Metabolic causes:
Vitamin deficiencies
Thyroid disease
Hereditary ataxias
Adult-onset leukodystrophy, such as adult-onset adrenoleukodystrophy
Uncommon genetic etiologies:
Mitochondrial cytopathy
Fabry disease
Alexander disease
Hereditary spastic paraplegia
Neoplastic causes include primary CNS malignancies, such as gliomas and meningiomas,
or metastasis
Prognosis
The prognosis and severity of multiple sclerosis vary widely among patients,[41] and the disease
often exhibits mild symptoms early, which worsens over time.
Factors that suggest a worse prognosis include:
Male gender
Progressive course
Primarily pyramidal or cerebellar symptoms
More frequent relapses
Minimal recovery between relapses
Multifocal onset
High early relapse rate
Large lesion load and brain atrophy on MRI
Factors that suggest a favorable diagnosis include:
Female gender
Relapsing course
Mild relapses
Good recovery between exacerbations
Primarily sensory symptoms
The long interval between the first and second relapses
Low lesion load on MRI
Presentation of optic neuritis
Full recovery from exacerbations
Complications
Long-term disability in multiple sclerosis results from incomplete recovery after each relapse,
leading to an accumulation of symptoms over time.
Impaired mobility is observed in most long-term multiple sclerosis patients due to various
factors. The reduction in mobility is multifactorial and possibly related to defective motor
control and vestibular symptoms.
Brain stem lesions involving the oculomotor pathways can cause chronic diplopia, which
may be managed with prisms or surgery.
Chronic vertigo, another common issue, is a possible source of morbidity and may respond
to medications such as meclizine, ondansetron, or diazepam.
Chronic dysphagia due to bulbar dysfunction can lead to chronic aspiration.
Cerebellar tremors can potentially significantly affect a person's disability. While wrist
weights may help manage tremors, potential superimposed weakness can preclude their
use.
Urinary tract infections, considered long-term complications, can occur due to bladder
dysfunction, which often necessitates consultation with urology specialists.
Constipation is the most frequent gastrointestinal complication, and this issue can be
managed with patient education, increased fiber intake, and bulk-forming agents.
Erectile dysfunction is treated with oral phosphodiesterase-5 inhibitors if present.
Cognitive impairment, mood disorders, and generalized fatigue are considered long-term
sources of morbidity, and they are managed in various ways, often involving subspecialty
care.
Consultations
Multiple sclerosis is a complex neurological disorder that leads to various neurological and non-
neurological symptoms, disabilities, and complaints. A comprehensive team approach involves
specialists from:
Neurology and neuro-ophthalmology
Psychiatry and cognitive psychology
Pain management
Nursing and physician assistants
Speech therapy
Occupational therapy
Social work
Physical medicine and rehabilitation
Urology (in the setting of genitourinary complications)
Gastroenterology (in the setting of gastrointestinal complications)
Deterrence and Patient Education
Diagnosing multiple sclerosis can be challenging for patients, and clinicians play a crucial role in
providing supportive counseling regarding the diagnosis. Predicting the disease course is
complex, so clinicians must educate patients about the varied possibilities in disease progression.
In addition, it is important to emphasize that many patients respond well to treatment and to
explain the role of effective medications. Patients should also be directed to reputable online
sources such as the Multiple Sclerosis International Federation and the National Multiple
Sclerosis Society to learn more about their condition. Educating patients about the nature of
relapses and long-term complications is also vital.
Patients should be informed to contact their treating clinician promptly if they experience new
neurological symptoms lasting more than 24 hours, as this may require corticosteroid
administration. In addition, it is crucial to emphasize smoking cessation, take vitamin D
supplementation, maintain a balanced diet, and adhere to lifestyle modifications. Patients should
also receive counseling on the significance of adhering to disease-modifying therapy, considering
the adverse effect profile of these medications.
Enhancing Healthcare Team Outcomes
Multiple sclerosis is a complex disease process presenting with sensory, visual, weakness,
coordination, and spasticity issues. Other health concerns include bladder and bowel dysfunction,
depression, cognitive impairment, fatigue, sexual dysfunction, sleep disturbances, and vertigo.
Due to its multisystem impact and reduced life expectancy, optimal management of multiple
sclerosis necessitates an interprofessional healthcare team, including neurologists, pain
specialists, therapists, nurse specialists, ophthalmologists, mental health nurses,
gastroenterologists, urologists, nurses, and pharmacists, who can treat patients with multiple
sclerosis.
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Figure
Optic Neuritis as an Indicator of Multiple Sclerosis. Optic
neuritis can be visualized through fundoscopy, which may
indicate the presence of multiple sclerosis. Contributed by S
Bhimji, MD
Figure
Perivascular Plaques in Multiple Sclerosis as Seen in MRI.
The MRI image reveals perivascular plaques in multiple
sclerosis, with relatively decreased perivascular inflammation
compared to active plaques. Contributed by S Munakomi,
MD
Figure
Sagittal FLAIR Sequence Demonstrating a Hyperintense
Lesion on MRI. The image shows a sagittal FLAIR sequence
on MRI, highlighting a hyperintense lesion, a characteristic
feature known as "Dawson fingers," frequently seen (more...)
Figure
Axial FLAIR Sequence Demonstrating an Advanced Lesion
Burden on MRI. The image shows an axial FLAIR sequence
on MRI, highlighting an advanced lesion burden along the
callososeptal interface, a characteristic finding in multiple
sclerosis. Contributed (more...)
Figure
Sagittal FLAIR MRI Brain Image Demonstrating Linear
Hyperintense Lesions. The sagittal FLAIR image highlights
linear hyperintense lesions perpendicular to the left lateral
ventricle, a characteristic feature known as "Dawson fingers,"
commonly observed (more...)
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