CNS DEMYLINATING DISORDERS Multiple sclerosis
A Dutch saint named Lidwina, who died in 1433, may have been one of the first known MS patients. After she fell while ice skating, she developed symptoms such as
excruciating pain and paralysis. Her condition got worse over the course of her life, but she did have remissions. Another well-known potential MS patient was a grandson of King George III, who described his symptoms in a diary that he kept until his death in 1848.
Twenty years later, Dr. Jean-Martin Charcot became the first person credited with identifying multiple sclerosis as a disease. A female patient of his suffered an unusual combination of symptoms. He tried some of the typical treatments for other
neurological disorders, such as electrical stimulation and injections of silver (which helped alleviate the symptoms of syphilis), but none of them worked. After his patient died, he dissected her brain and discovered the brain lesions. He called the disease sclerose en plaques.
Multiple sclerosis (MS) affects women more than men. The disorder is most commonly diagnosed between ages 20 and 40, but can be seen at any age.
MS is caused by damage to the myelin sheath, the protective covering that surrounds nerve cells. When this nerve covering is damaged, nerve signals slow down or stop. The nerve damage is caused by inflammation. Inflammation occurs when the body's
own immune cells attack the nervous system. This can occur along any area of the brain, optic nerve, and spinal cord.
It is unknown what exactly causes this to happen. The most common thought is that a virus or gene defect, or both, are to blame. Environmental factors may play a role.
Symptomatology Numbness or weakness in one or more limbs
Partial or complete loss of central vision, usually in one eye, often with pain during eye movement (optic neuritis)
Double vision or blurring of vision Tingling or pain in parts of your body
Tremor, lack of coordination or unsteady gait Slurred speech
Fatigue Dizziness
Relapsing remitting MS (RRMS) is present in 85% to 90% of patients at diagnosis. This subtype is characterized by relapses and remissions that can last months to years without development of new symptoms. Approximately 65% of these patients will progress to secondary progressive MS. New episodes occur erratically, but the rate seldom exceeds 1 to 5 episodes per year.
Secondary progressive MS (SPMS) is arguably not a classification of its own but rather the second stage of RRMS. The median time span between diagnosis of RRMS and progression to SPMS is 19 years, with men often experiencing more rapid progression than women; the older the patient is at presentation, the faster the progression. Also, motor or long-tract symptoms have been associated with earlier conversion. The disease course includes distinct exacerbations with no symptom-free remissions; instead, patients will experience progressive neurocognitive decline.
Primary progressive MS (PPMS) is responsible for 10% to 15% of cases. Unlike patients with SPMS, who have a period of RRMS and recovery phases, those with PPMS steadily decline from diagnosis, with no remission.
Progressive relapsing MS (PRMS) is the least common subtype. Patients experience a constant decline that includes exacerbations without any symptom-free remissions.
Disease modifying agents
Beta interferons. These types of drugs — such as Avonex, Betaseron, Extavia and Rebif — appear to slow the progress of multiple sclerosis, reduce the number of attacks and lessen the severity of attacks. Interferons can cause many side effects, including reactions in the injection area and liver damage. However, it's rare to have serious, permanent side effects. You'll likely need blood tests to monitor your liver function and blood count.
Glatiramer acetate (Copaxone). This medication may reduce the number of MS attacks. Doctors believe that glatiramer acetate works by blocking your immune system's attack on myelin. You must inject this drug under your skin (subcutaneously) once daily. Side effects are uncommon, but may include flushing, chest pain or heart palpitations after injection and reactions at the injection sites.
Fingolimod (Gilenya). An oral medication given once daily, this works by trapping immune cells in lymph nodes. It may reduce attacks of MS and short-term disability. To take this drug, you'll need to have your heart rate monitored for six hours after the
first dose because the first dose can slow your heartbeat (bradycardia). You'll also need to be immune to the chickenpox virus (varicella-zoster virus). Other side effects may include diarrhea, cough and headache.
Natalizumab generally is reserved for people who see no results from or can't tolerate other types of treatments. This medication increases the risk of progressive multifocal leukoencephalopathy (PML) — a brain infection that usually is fatal.
A blood test helps detect whether you've been exposed to the JC virus, a virus that causes PML, before or while taking this medication. This virus, as well as other risks, may cause development of PML in people taking this medication. Other side effects of
Mitoxantrone. This immunosuppressant medication can be harmful to the heart, and it's associated with development of blood cancers like leukemia. Because of these risks, it's usually only used to treat active severe, advanced multiple sclerosis, based on both clinical assessment and MRI studies.
Teriflunomide (Aubagio). This oral medication reduces attacks and lesions in people with MS. You'll need blood tests to monitor liver function, as it may cause serious liver damage. It can also cause serious fetal damage, and it must not be taken during pregnancy. It may also cause side effects such as diarrhea and nausea.
The medication stays in your system for months. If you have complications, additional medications must be administered in order to help your body rapidly eliminate the drug.
Prognosis
The severity of the disease, and how the disease progresses, varies widely from patient to patient and is unpredictable. About 20% of patients remain asymptomatic or become only mildly symptomatic after an initial clinical event. Another 20% experience a rapidly progressive condition. Most patients, however, will have some degree of disease progression.
Women tend to have a better outlook than men. Factors that determine a higher risk for a severe condition include:
Age over 40 years at the time of onset of symptoms
Initial symptoms that affect motor control, mental functioning, or urinary control Initial symptoms that affect multiple regions of the body
Attacks in the first years that are frequent, or a short time between the first two attacks Incomplete remissions
Rapid progression to disability
MS that is progressive from the beginning or becomes progressive shortly after the onset
Neuromylitis optica
Neuromyelitis optica is an uncommon, idiopathic, demyelinating syndrome of the central nervous system that preferentially affects the optic nerves and spinal cord. It frequently is misdiagnosed as severe multiple sclerosis, but usually is readily
distinguished from multiple sclerosis in fully developed cases because of its severity, typical magnetic resonance imaging (MRI) findings (normal brain MRI longitudinally extensive lesions on spinal cord MRI), and cerebrospinal fluid analysis
(polymorphonuclear pleocytosis and absence of oligoclonal banding). A serum auto-antibody marker, NMO-IgG, is highly specific for the disorder.
Most patients have relapsing disease, and natural history studies confirm early and severe disability. We treat acute myelitis and optic neuritis exacerbations with
parenteral corticosteroids and use rescue plasmapheresis for severe, refractory attacks. Immunomodulatory drugs used for typical multiple sclerosis seem ineffective for relapse prevention. We recommend systemic immunosuppression, usually with azathioprine and oral cortico-steroids, for most patients. Fulminant disease and breakthrough disease may respond to other forms of humoral immunotherapy such as rituximab.
Acute disseminated encephalomylitis
Clinically, acute disseminated encephalomyelitis (ADEM) is usually readily distinguishable from multiple sclerosis (MS) by the presence of certain clinical features, including the following: History of preceding infectious illness or immunization
Association with constitutional symptoms and signs such as fever Prominence of cortical signs such as mental status changes and seizures
Comparative rarity of posterior column abnormalities, which are common in MS Age younger than 11-12 years in ADEM and age older than 11-12 years in MS
