Multiple Sclerosis Flashcards
what is the definition of MS?
Multiple sclerosis (MS) is defined as an inflammatory demyelinating disease characterised by the presence of episodic neurological dysfunction in at least two areas of the central nervous system (brain, spinal cord, and optic nerves) separated in time and space
what is the epidemiology of MS?
Between 20-40
Caucasain
Females - early and more common
Geographic - nearer the poles?
what is the aetiology of MS?
Genetics - While the genetics of MS are multifactorial, genes in the human leukocyte antigen (HLA) region and the interleukin region are likely to be involved.
Environment - toxins, viral exposure, and sunlight exposure (and its effect on vitamin D metabolism)
EB virus protective if contracted early in life, detrimental is later in life
what are the risk factors for MS?
Female
Family history
Northern latitude
what is the pathophysiology of MS?
The precise pathogenesis of MS is unknown. There is no specific or sensitive antigen or antibody, and there is some debate about whether MS represents a single disease or a syndrome of pathogenetically heterogeneous patient subgroups. Conceptualisations of MS immunopathology involve 2 distinct but overlapping and connected phases, inflammatory and degenerative.
During the initial stage of the inflammatory phase, lymphocytes with encephalitogenic potential are activated in the periphery by factors such as infection or other metabolic stress. These activated T cells seek entry into the central nervous system (CNS) via attachment to a receptor on endothelial cells. This interaction, mediated by production of matrix metalloproteinases, allows a breach in the blood-brain barrier, leading to further upregulation of endothelial adhesion molecules and additional influx of inflammatory cells. The T cells produce inflammatory cytokines that cause direct toxicity and also attract macrophages that contribute to demyelination. Epitope spread occurs early and contributes to the complexity of immunopathology.
The degenerative component of MS is believed to reflect axonal degeneration and loss. Demyelination disrupts axonal support and leads to destabilisation of axonal membrane potentials, which causes distal and retrograde degeneration over time. There is also a suggestion that inflammatory cells, antibodies, and complement may contribute to axonal injury. Axonal damage has been identified in regions of active inflammation, indicating that it begins early in the disease process
Pathologically, MS is characterised by multifocal areas of demyelination, loss of oligodendrocytes, and astrogliosis with loss of axons primarily in the white matter of the CNS, although cortical lesions may also play a significant role. Clinical heterogeneity and studies of biopsy and autopsy specimens suggest that the mechanisms leading to tissue damage differ from patient to patient
what are the key presentations of MS?
Visual disturbances in one eye and pain
Peculiar sensory phenomena - odd sensations of a patch of wetness or burning, or hemibody sensory loss or tingling
Arm and leg weakness
Sensory symptoms
Lhermitte’s sign - shooting down spine if cervical spine flexed
Nystagmus
Bladder dysfunction
what are the signs of MS?
Female 20-40 Increased deep tendon reflexes Foot dragging or slapping Nystagmus Dysarthria Lhermitte’s sign - shooting down spine if cervical spine flexed
what are the symptoms of MS?
Visual disturbances in one eye and pain Peculiar sensory phenomena Leg and arm cramps and weakness Bowel problems Urinary incontinence Trigeminal neuralgia
what are the first line and gold standard investigations for MS?
Clinical diagnosis - eye movements, arm movements to test pyramidal weakness, grip strength, reflexes, finger jerk reflex, touch to test sensation , touch nose then finger, fun finger along foot, take history in along with below tests:
MRI brain - hyperintensities in the periventricular white matter; most sensitive images are sagittal FLAIR
MRI spinal cord - demyelinating lesions in the spinal cord, particularly the cervical spinal cord; detection of alternate diagnosis, such as cervical spondylosis
FBC - normal (to rule out other)
Comprehensive metabolic panel - normal
TSH - normal
Vitamin B12 - normal
CSF electrophoresis - oligoclonal IgG banding present in 80% of MS
Two or more CNA lesions disseminated in time and space, and exclusion of conditions giving similar clinical picture
what are the differential diagnoses of MS?
Myelopathy due to cervical spondylitis
Fibromyalgia
Postural orthostatic tachycardia
how is MS managed?
Treat progressive and aggressive illness, treat early and progressive. Steroids for relapses and plasma exchange if this doesn’t work, multiple replasses = disease modifying agents (Interferon etc.)
Acute relapse:
Methylprednisolone and plasma exchange
Relapsing-remitting:
Immunomodulators (interferon beta 1a), management of symptoms
Secondary progressive:
Siponimod or methylprednisolone or cladribine, management of symptoms
Primary progressive:
Coinsider ocrelizumab, management of symptoms
how is MS monitored?
Patients who are experiencing a relapse should be seen by their healthcare provider at the time of the relapse or soon after to determine if there is any need for acute management, and to assess the impact of the relapse on their choice of ongoing therapy.
Most patients need to be seen only every 6 to 12 months if they are relatively stable and not requiring medication changes in either their symptomatic or disease-modifying therapy.
what are the complications of MS?
Side effects of steroids and interferon injections
UTIs
Osteopenia and osteoporosis
Depression
what is the prognosis of MS?
Partial recovery - colours dimer for patients with vision loss etc.
It is very difficult to prognosticate effectively for patients with MS. Some patients have a very benign course and/or respond well to treatment, whereas others become rapidly disabled within several years of diagnosis.
10% = Benign, mild disease
30% = pregressive disease
Death tends to be due to complications rather than MS
Poor prognosis = male, cerebellar symptoms early, short interattack interval, late age onset, MRI lesions significance, positive bands on CFS
