Multiple Sclerosis


Article Author:
William Gossman
Moavia Ehsan


Article Editor:
Kathryn Xixis


Editors In Chief:
Laurie Graham
Andrew Wilt
Mary Cataletto


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Frank Smeeks
Kristina Soman-Faulkner
Trevor Nezwek
Radia Jamil
Patrick Le
Sobhan Daneshfar
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
7/12/2019 12:03:06 AM

Introduction

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) characterized by chronic inflammation, demyelination, gliosis, and neuronal loss. The course may be relapsing-remitting or progressive in nature. Lesions in the CNS occur at different times and in different CNS locations. Because of this, multiple sclerosis lesions are sometimes said to be "disseminated in time and space." The clinical course of the disease is quite variable ranging from a stable chronic disease to a rapidly evolving and debilitating illness. The most common form of the disease is relapsing-remitting multiple sclerosis; however, several other forms exist.[1][2][3]

Etiology

The specific cause of multiple sclerosis is unknown. The most widely accepted theory is that multiple sclerosis is an autoimmune disease that preferentially destroys the CNS while the peripheral nervous system is spared. Demyelination causes the symptoms of multiple sclerosis. Damage to myelin, the protective fatty tissue around the nerves that aids conduction of impulses along the nerves, leads to symptomatic flares in multiple sclerosis. These damaged areas often do not fully recover leading to areas of scarring, damage, and ongoing symptoms.  Over time, these cumulative areas of damage can lead to disability. Of note, patients can also develop subclinical areas of damage that are detectable early in the disease course only by radiographic studies.[4][5][6]

Epidemiology

Approximately 350,000 individuals in the United States and 2.5 million individuals worldwide have multiple sclerosis. The disease is 3-fold more common in females than in males. While the age of onset is usually between 20 to 40 years, the disease can present at any age. Almost 10% of the cases present before the age of 18.[7]

Classically, multiple sclerosis is more common in populations who live farther from the equator. The highest prevalence of multiple sclerosis is found in Orkney islands north of Scotland. In other temperate areas like North America, northern Europe, southern Australia and southern New Zealand the prevalence of the multiple sclerosis is significantly higher than in areas closer to the equator.

A variety of risk factors for multiple sclerosis have been suggested. In addition to increasing risk with increasing distance from the equator, genetic associations, sunlight exposure, vitamin-D levels, tobacco smoking, viral transmission, and other theories have been evaluated.  No theory has been proven.

Pathophysiology

Early lesions of multiple sclerosis show mononuclear infiltrate with perivenular cuffing and surrounding white matter infiltration. The blood-brain barrier is disrupted at inflammatory sites. However, the vessel wall is preserved. The humoral immune system may also play a significant role in disease pathogenesis as evident by the presence of B-cells at active sites. The pathological hallmark of multiple sclerosis is demyelination which is often the earliest sign noted in affected neurons. Oligodendrocyte precursor cells usually survive and are often present in greater number when compared to the surrounding normal tissue, but, these cells fail to differentiate into mature oligodendrocytes. In some lesions, there is partial remyelination of surviving neurons, known as shadow plaques. With the evolution of a lesion, astrocytes proliferate resulting in gliosis.

Myelin is known to aid in the conduction of nerve impulses. Because multiple sclerosis is a demyelinating disease resulting in damage to this myelin, conduction speed is often slowed along affected nerves leading to the symptoms seen in multiple sclerosis.

Histopathology

When hematoxylin and eosin (HE) stain is done, the plaques of multiple sclerosis appear pale when compared to normal white matter. Active lesions are also cellular as they contain inflammatory cells like macrophages, lymphocytes, and astrocytes. Often, activity is confined to the borders of the plaques and myelin staining shows complete loss of myelin or palor of the myelin sheaths. The inflammatory cells of the lesions include CD8 T lymphocytes, macrophages, microglia, and astrocytes. B lymphocytes, plasma cells, antibodies, and complement proteins have also been identified in the lesions. Lesions are most frequently found in the periventricular white matter, optic nerves, and the spinal cord in multiple sclerosis.  Lesions in the periventricular white matter often caused "Dawson's fingers."

History and Physical

The presentation of multiple sclerosis is variable. Classic presentations include sensory changes, weakness, or visual changes. The most common presenting symptoms are unilateral sensory disturbances. Unilateral visual changes, often in the form of optic neuritis, are also quite common.

Often patients will present with a history of sensory, weakness, or visual changes which have occurred and resolved. Because symptoms often resolve without specific medical intervention, patients may have a history of several different events prior to presenting for formal medical evaluation.

As stated, sensory changes are common. These can affect any part of the body but are often unilateral. Likewise, weakness may affect any part of the body. Optic neuritis presents with decreased visual activity, dimness of vision, and decreased color perception known as red desaturation. Abnormality of the affected pupil to respond to light called afferent pupillary defect is often seen in cases of optic neuritis. Another common visual complaint is of abnormal eye movement known as internuclear ophthalmoplegia (INO). Patients often complain of diplopia. INO results from a demyelinating lesion of the medial longitudinal fasciculus.

Patients with a history of demyelinating damage may state that symptoms worsen in extreme heat. This is known as Uthoff's phenomenon. Patients may also complain of electrical sensation moving through the spine and limbs. This is known as Lhermitte's sign.

Multiple sclerosis is a complex disease. In addition to sensory changes, weakness, and visual changes, coordination problems or spasticity can be seen. Other complaints related to general health include bladder and bowel dysfunction, cognitive impairment, depression, fatigue, sexual dysfunction, sleep problems, and vertigo.

Evaluation

The diagnosis of multiple sclerosis is a clinical diagnosis. No one test is diagnostic for the disease. Evidence of lesions which have occurred at different times in different locations must be found. This evidence can be clinical or radiographic. When evaluating clinical flares, flares are traditionally defined as symptoms that last for at least 24 hours. The McDonald Criteria is a set of criteria outlining different ways that a patient can meet the criteria for a definite diagnosis of multiple sclerosis.[8][9][10]

MRI is the radiologic study of choice. MRI should be completed with and without contrast to help differentiate old lesions from new, active lesions. Cerebrospinal fluid (CSF) analysis may be helpful in pointing toward a diagnosis of multiple sclerosis. Specifically, the presence of oligoclonal bands present in the cerebrospinal fluid which are not present in the serum is concerning for an underlying diagnosis such as multiple sclerosis. It is important to evaluate for other mimickers of multiple sclerosis as well. These include a wide variety of other neurologic diseases, rheumatologic diseases, and infectious diseases.

Treatment / Management

At least partial recovery from acute exacerbations or flares is expected. However, as discussed above, repair of damaged myelin may be incomplete.[11][12][13]

Flares are often treated with steroids. Steroids lead to a faster recovery from an acute attack but do not change the ultimate extent of recovery. Furthermore, steroids do not prevent future attacks.

The primary goal in the treatment of multiple sclerosis is to prevent areas of damage by using maintenance therapies. Early maintenance therapies were injectables and first became available in the 1990s. Rapid growth has occurred in this area in the past several years with injection therapies, oral therapies, and infusion therapies now available. Therapies have largely targeted relapsing-remitting multiple sclerosis, the most common form of the disease. However, in 2017, the first therapy was approved for another form of the disease, primary progressive.[14][15]

Differential Diagnosis

The differential diagnosis for multiple sclerosis is broad. Other related neurologic diseases such as neuromyelitis optica must be ruled out. A wide variety of rheumatologic diseases and infectious diseases must also be screened for when a diagnosis of multiple sclerosis is considered.

Enhancing Healthcare Team Outcomes

Multiple sclerosis is a complex disease. In addition to sensory changes, weakness, and visual changes, coordination problems or spasticity can be seen. Other complaints related to general health include bladder and bowel dysfunction, cognitive impairment, depression, fatigue, sexual dysfunction, sleep problems, and vertigo. Because of the shortened life expectancy and multisystem involvement, the disorder is best managed by a multidisciplinary team that includes a neurologist, therapist, pain specialist, nurse specialist, ophthalmologist, mental health nurse, gastroenterologist and a urologist. Because there is no cure, it is vital to ensure that the patient's quality of life is not eroded. Social work must be involved early in the care and the patient provided with all the possible supportive assistance.[16] (Level V)


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Multiple Sclerosis - Questions

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What is the most common demyelinating disease of the brain?



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A patient has high T2 signal intensity lesions in the white matter of the optic nerves or spinal cord. What is the the most likely diagnosis?



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What will the lumbar puncture most likely show a patient with suspected multiple sclerosis?



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A 33-year-old female has been having headaches and urinary incontinence sporadically. She also complained of painful tingling sensation in her face in the past. However, during the recent warm summer and heat waves, she has been complaining of worsening of her symptoms and in addition has developed problems with her gait. She most likely has what disease?



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A 40-year-old female with urinary incontinence presents with left eye blurred vision and intermittent diplopia. These changes have been ongoing for the past 3 months. What test should be performed next?



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A female with varying neurological symptoms is found to have fibrillary gliosis and a marked reduction of oligodendroglia. There is some evidence of demyelination. Which of the following is the most likely diagnosis?



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The MacDonald criteria are often used to do which of the following?



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A 42-year-old male presents with two attacks of transient visual loss and urinary incontinence. T2 weighted MRI images reveal several ovoid areas of signal enhancement in the parietal lobe. He states that he is just tired but otherwise feels fine. What is the next step in his investigation?



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A young patient presents after having paresthesias of her left leg lasting several days. By the time of her appointment the symptoms have almost resolved. Additional history includes a bout of visual blurring in her right eye years ago that resolved over a few weeks. She has no other complaints. Examination is normal except for hyperreflexia in her right leg. What would be the best examination to reveal her diagnosis?



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Lhermitte sign is occasionally seen in multiple sclerosis patients. How can it be best described?



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A patient with suspected multiple sclerosis undergoes testing. Which result would be rule out multiple sclerosis as a diagnosis?



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A 35-year-old man presents with known relapsing-remitting multiple sclerosis. His history dates back 4 years with a bout of right optic neuritis initially followed by another event two years ago of right hemi-sensory loss. He has not had any further attacks since then and is not currently receiving any treatment. What is the best recommendation at the current time?



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Of the following initial neurologic complaints, which one offers the BEST prognosis for a newly diagnosed multiple sclerosis patient?



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A middle aged patient presents with progressive spastic paraparesis developing over a few weeks. History includes that he underwent basilar tip aneurismal clipping a year earlier for intermittent diplopia. He also describes prior bouts of numbness in the right side of his body and now also has incontinence. Recent CT head and CT angiography show the aneurismal clipping to be stable. Which of the following tests would be most helpful as a next step?



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A patient with a twenty year history of active relapsing-remitting multiple sclerosis with bladder complaints will most likely show which of the following on urinary and bladder function testing?



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A patient with longstanding multiple sclerosis is suffering from progressive leg spasticity and muscle spasms. Which of the following is NOT an appropriate medication consideration for treatment?



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A 26-year-old woman presents with acute pain and loss of vision in her left eye. Examination reveals poor gait with imbalance, right hemiataxia, diffuse hyperreflexia, and slightly slurred speech. EEG is normal as is head CT without contrast. Which of the following is her likely diagnosis?



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What is the most common presentation of multiple sclerosis?



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Which is the most important occupational therapy intervention in a patient with multiple sclerosis?



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What percentage of adult patients with multiple sclerosis will develop trigeminal neuralgia?



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A 20 year old previously healthy male complains about loss of sensation at the left upper extremity progressing over 2 days. He reports that he had flu-like symptoms for a week and these symptoms occurred subsequently. The numbness began in the hand and progressed to involve the entire left arm. Laboratories were normal but the MRI was abnormal. T2 weighted images show cerebral areas of high signal abnormalities. Which of the following pathologic changes are most likely?



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A 28-year-old female has developed enuresis over the past 5 weeks. She has a 2-week history of pins and needle sensation on her left thigh. Exam shows slight gait ataxia, inability to tandem walk, and hyperreflexia of both legs. MRI shows multiple areas of demyelination. What would a lumbar puncture show?



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What drug is part of the long-term armamentarium in modifying a gradually progressive course in relapsing-remitting multiple sclerosis?



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A 32 year old female has had recurrent symptoms of paresthesias in the extremities, difficulty swallowing, fatigue, and muscle paresis. Because the symptoms have been becoming progressively more severe, she is seeking medical help. She noticed the symptoms worsened during the very hot summer. What is the most likely diagnosis?



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Which subtype of multiple sclerosis routinely has periods of complete remission of symptoms between attacks?



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What is the most common type of multiple sclerosis (MS)?



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Which of the following is most likely linked to multiple sclerosis?



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Which of the following cells is most likely responsible for multiple sclerosis?



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A 38-year-old female presents with episodic attacks of transient visual loss and urinary incontinence. T2 weighted MRI images reveal numerous ovoid areas of signal enhancement. She states that, though she is somewhat fatigued today, she otherwise feels fine. Which of the following treatments is appropriate?



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A 23-year-old female volunteered at a school carnival for a day and had to stand for 8 hours. She noted that her right foot felt cold and her right leg had pins and needles. The symptoms resolved in about a week. She had mild low back pain but no symptoms at the left lower extremity. Three years ago the patient had optic neuritis that responded to treatment with corticosteroids and has not recurred. MRI at that time was normal. She has no other past medical history but is on oral contraceptives. She does not use illicit drugs but drinks alcohol occasionally. Exam shows Babinski in the left, brisk reflexes, and clonus at the left ankle. What is the most likely diagnosis?



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Which of the following findings is most likely on analysis of cerebrospinal fluid in patients with multiple sclerosis?



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A 37-year-old female with multiple sclerosis had initial presentation 5 years ago with optic neuritis that completely resolved without treatment. 3 years ago she had sensory and motor involvement of the upper extremities and was treated with corticosteroids. 2 years ago she was treated with interferon beta-1A. 3 days ago she developed decreased sensation of the left lower trunk without tingling, pain, gait problems, bowel or bladder problems, or systemic symptoms. Exam shows normal visual fields with a right afferent pupillary defect. There is decreased sensation to light touch over the right trunk. Rapid alternating movements, finger tapping, heal tapping to shin, and finger to nose are all-normal. Select the appropriate treatment.



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Select the test that is most commonly abnormal in early multiple sclerosis.



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Which of the following would be appropriate treatment for a patient with multiple sclerosis, leg weakness, and severe leg spasms limiting ambulation?



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A 27-year-old female with no past medical history presents to the emergency department with left eye pain and decreased perception of light. The exam is also remarkable for poor rapidly alternating movement of the right hand and slurred speech. Both eyes show ocular dysmetria and tandem gait is very unsteady. EEG is normal. What is the most likely diagnosis?



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Which of the following can be used to combat spasticity associated with multiple sclerosis (MS)?



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A patient with MS becomes too fatigued while engaging in sexual activity to enjoy himself. Select the best recommendation.



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A patient with multiple sclerosis is admitted to an acute care facility and is referred to OT. The patient complains of fatigue during strengthening activities. What should the therapist do?



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The pathogenesis of multiple sclerosis is linked to which cells?



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A 23 year old occupation therapy student is diagnosed with multiple sclerosis and referred for OT as she has fatigue, visual disturbance, and decreased lower extremity strength. The patient states that her major hope is to finish her classes and graduate on time. What should the OT do?



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Which of the following is the consequence of neuronal demyelination in multiple sclerosis?



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A patient is referred for multiple sclerosis to a physical therapist. The patient participates fully without complaint. At the next session, a couple of days later, the patient reports that she was weak, fatigued, and in pain the next day. Today she is back to baseline. Select appropriate management



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Select the most common presenting symptom or finding in multiple sclerosis.



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Which of the following is true of multiple sclerosis?



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Which of the following is true of the symptoms of multiple sclerosis (MS)?



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Which of the following is among the most common early symptom of multiple sclerosis?



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Which of the following medications has been reported to have a possible rebound effect on lesions of the brain (shown on MRI) after withdrawal in the treatment of multiple sclerosis?



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In what percentage of multiple sclerosis patients is cerebrospinal fluid (CSF) is abnormal?



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Considering multiple sclerosis cord plaques, what feature is most characteristic?



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How can you distinguish tumefactive multiple sclerosis (MS) from tumor?



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A 17-year-old female with complaints of diplopia that started a week ago. History reveals that she was also seen in the neurology clinic 2 months ago with lower extremity weakness. Today the physical exam shows optic nerve edema on fundoscopic exam and hyperreflexia in her legs with decreased pain, temperature, and vibration sense?



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At what age does multiple sclerosis most commonly present?



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Which of the following is elevated in the cerebrospinal fluid of patients with multiple sclerosis?



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Which of the following would be the first step in diagnosing multiple sclerosis?



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What is the best initial treatment for acute exacerbation of multiple sclerosis?



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Which of the following statements about multiple sclerosis is correct?



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A male college student is not able to adduct the left eye when looking to the right or to adduct the right eye when looking to the left. The most likely diagnosis:



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A patient has been diagnosed with multiple sclerosis (MS). Which of the following is considered first line therapy in the treatment of MS?



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A 29-year-old white female presents with a four-month history of pins and needle sensations in her right leg. She also states that her clumsiness has increased and she is unable to hold a cup of coffee. Last week, she saw an ophthalmologist because she had visual blurring and pain in the right eye. She has been booked for an evaluation of urinary incontinence that started a month ago. She denies any trauma, use of drugs or any recent illness. Except for some confusion, the exam today appears to be near normal. Based on this history, what typical findings on an MRI will be observed?



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Which of the following drug is FDA approved to improve the walking capacity of patients with multiple sclerosis?



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A 24-year-old woman presents to the with fatigue, weakness, blurred vision, and a tingling sensation in her hands. Initial evaluation including MRI is normal. Lumbar puncture is performed. Analysis of her cerebrospinal fluid shows the presence of oligoclonal bands and elevated protein levels. Based on this finding, what medical condition could potentially be one of your differential diagnoses?



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A 29-year-old male patient presents with numbness and tingling to his hands and legs and stiffness to muscles and joints in both legs. Which of the following tests should the healthcare provider perform first to rule out multiple sclerosis?



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Multiple Sclerosis - References

References

Konuskan B,Anlar B, Treatment in childhood central nervous system demyelinating disorders. Developmental medicine and child neurology. 2019 Apr 16;     [PubMed]
Kaur J,Ghosh S,Sahani AK,Sinha JK, Mental imagery training for treatment of central neuropathic pain: a narrative review. Acta neurologica Belgica. 2019 Apr 15;     [PubMed]
Pape K,Tamouza R,Leboyer M,Zipp F, Immunoneuropsychiatry - novel perspectives on brain disorders. Nature reviews. Neurology. 2019 Apr 15;     [PubMed]
Cree BAC,Mares J,Hartung HP, Current therapeutic landscape in multiple sclerosis: an evolving treatment paradigm. Current opinion in neurology. 2019 Apr 9;     [PubMed]
Ryan P,Xu M,Davey AK,Danon JJ,Mellick GD,Kassiou M,Rudrawar S, The O-GlcNAc modification protects against protein misfolding and aggregation in neurodegenerative disease. ACS chemical neuroscience. 2019 Apr 15;     [PubMed]
Schweitzer F,Laurent S,Fink GR,Barnett MH,Reddel S,Hartung HP,Warnke C, Age and the risks of high-efficacy disease modifying drugs in multiple sclerosis. Current opinion in neurology. 2019 Apr 9;     [PubMed]
Magyari M,Sorensen PS, The changing course of multiple sclerosis: rising incidence, change in geographic distribution, disease course, and prognosis. Current opinion in neurology. 2019 Mar 28;     [PubMed]
Sherif M,Bergin C,Borruat FX, Normal Visual Recovery after Optic Neuritis Despite Significant Loss of Retinal Ganglion Cells in Patients with Multiple Sclerosis. Klinische Monatsblatter fur Augenheilkunde. 2019 Apr;     [PubMed]
Schmierer K,Campion T,Sinclair A,van Hecke W,Matthews PM,Wattjes MP, Towards a standard MRI protocol for multiple sclerosis across the UK. The British journal of radiology. 2019 Apr 17;     [PubMed]
Hartung HP,Graf J,Aktas O,Mares J,Barnett MH, Diagnosis of multiple sclerosis: revisions of the McDonald criteria 2017 - continuity and change. Current opinion in neurology. 2019 Apr 9;     [PubMed]
Van Der Walt A,Nguyen AL,Jokubaitis V, Family planning, antenatal and post partum care in multiple sclerosis: a review and update. The Medical journal of Australia. 2019 Mar 27;     [PubMed]
Hočevar K,Ristić S,Peterlin B, Pharmacogenomics of Multiple Sclerosis: A Systematic Review. Frontiers in neurology. 2019;     [PubMed]
Kim Y,Lai B,Mehta T,Thirumalai M,Padalabalanarayanan S,Rimmer JH,Motl RW, Exercise training guidelines for multiple sclerosis, stroke, and Parkinson's disease: Rapid review and synthesis. American journal of physical medicine     [PubMed]
Ömerhoca S,Akkaş SY,İçen NK, Multiple Sclerosis: Diagnosis and Differential Diagnosis. Noro psikiyatri arsivi. 2018;     [PubMed]
Krasniuk S,Classen S,Morrow SA,Tippett M,Knott M,Akinwuntan A, Clinical Determinants of Fitness to Drive in Persons With Multiple Sclerosis: Systematic Review. Archives of physical medicine and rehabilitation. 2019 Jan 26;     [PubMed]
Gullo HL,Fleming J,Bennett S,Shum DHK, Cognitive and physical fatigue are associated with distinct problems in daily functioning, role fulfilment, and quality of life in multiple sclerosis. Multiple sclerosis and related disorders. 2019 Apr 1;     [PubMed]

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