DR. SADIK AL-GHAZAWI CONSULTANT NEUROLOGIST MRCP, FRCP UK

numerous scars better known as  The name multiple sclerosis refers to the numerous scars better known as ( plaques or lesions) that develop on the white & gray of the brain and spinal cord over time. T & B cells disease.

Multiple sclerosis (MS) is a 1- Demyelinating in which the insulating covers of nerve cells in the brain and spinal cord are damaged. 2-This damage disrupts the ability of parts of the nervous system to communicate, resulting in a range of signs  and symptoms.

1- physical, mental and sometimes psychiatric including, 1- physical,  mental and sometimes psychiatric problems. 2-Specific symptoms can include- double vision, INO, optic neuritis blindness in one eye,

muscle weakness, trouble with sensation, &troubles with coordination, partial transverse myelitis, or clinically isolated syndrome (CIS) which 60 percent develop MS in 10 years. ,

Signs and symptoms (cont) 1-loss of sensitivity or changes in sensation such as tingling, pins and needles or numbness. 2-muscle weakness

3- very pronounced reflexes. 4-muscle spasms, or difficulty in moving. 5- difficulties with coordination and balance (ataxia).

6-problems with speech or swallowing. 7- visual problems (nystagmus ,optic neuritis  or double vision. 8-feeling tired, acute  or chronic pain, and 9-bladder and bowel difficulties,

such as depression or unstable mood are also common. 1110-difficulties thinking and emotional problems such as depression  or unstable mood are also common.

11-Uhthoff phenomenon, a worsening of symptoms due to exposure to higher than usual temperatures, 12-Lhermitte,sign, an electrical sensation that runs down the back when bending the neck, are particularly characteristic of MS.[

Rotatory nystagmus

Horizontal nystagmus

Ataxic gait

Intention tremor

3-The disease usually begins between the ages of 20 and 50 . 4- MS is twice as common in women as in man.   .

CLINICAL COURSE 1-relapsing-remitting MS (RRMS). secondary progressive MS (SPMS). primary progressive MS (PPMS).

The relapsing-remitting subtype. --80-85 present. --female predominant. 1- characterized by unpredictable rapid onset relapses followed by period of months or years of partial or complete recovery.

1-Attack is a symptoms or objectively observed signs suggestive demyelination process with duration of at least 24 hours, in the absence of fever or infection. 2-For paroxysmal symptoms (such as paroxysmal dysarthria, tonic spasms, or paroxysmal sensory symptoms) to be considered an attack, must be recurrent over at least 24 hours.

3-Once MS has been established ,we must evaluate for evidence of dissemination in space DIS (multiple areas) , and for dissemination in time DIT(ongoing disease activity over time).

2- Deficits that occur during attacks may either A-Resolve or leave problems  in about 40% of attacks. B-being more common the longer a person has had the disease.

3- When deficits always resolve between attacks, this is sometimes referred to as benign MS, although people will still build up some degree of disability in the long term.

The primary progressive subtype=- 1- occurs in approximately 10–20% of individuals, with no remission after the initial symptoms. 2- It is characterized by progression of disability from onset, with no, or only occasional and minor, remissions and improvements.

1- 10% to 15%. 2-insidious onset of symptoms followed by gradual deterioration over time. 3-Clinical disease in these patients typically presents as a progressive myelopathy, and less frequently as a brainstem or cerebellar syndrome.

Older. no clear gender predominance MRI lesions : fewer in number less likely to enhance with gadolinium compared to relapsing-remitting MS.

3- The usual age of onset for the primary progressive subtype is later than of the relapsing-remitting subtype. 4- It is similar to the age that secondary progressive usually begins in relapsing- remitting MS, around 40 years of age.

Secondary Progressive Multiple Sclerosis

1-25% to 40% of patients with relapsing remitting MS go on to a secondary progressive course after an average of about 20 years. 2-diagnosed when, after an initial relapsing-remitting course, a patient demonstrates disease progression independent of relapses for at least 6 months.

3-deterioration with respect to gait, balance, spasticity, and bladder function ,Many patients experience cognitive decline.

CLINICALLY ISOLATED SYNDROM (CIS) 1-the condition begins in 85% of cases as clinically isolated syndrome (CIS) . 2--45% having motor or sensory problems. 3--20% having optic neuritis, and

4--10% having symptoms related brain stem dysfunction, 5-while the remaining 25% have more than one of the previous difficulties

ETIOLOGY of MS The real cause of MS is unknown; however, it is believed to occur as a result of some combination of genetic and environmental factors such as=- 1-infectious agents.

Similarly, viral infections such as the common cold,  influenza or gastroenteritis increase their risk. 2- Stress may also trigger an attack  

2-Geography 1-MS is more common in regions with northern European populations. 2-the geographic variation may simply reflect the global distribution of these high-risk populations.

1-the probability of developing the disease is 3-Genetics 1-the probability of developing the disease is higher in relatives of an affected person, with a greater risk among those more closely related. 

EXAMPLE identical twins both are affected about 30% of the time, while around 5% for non-identical twins and

3-if both parents are affected the risk in their children is 10 times that of the general population. 4- MS is also more common in some ethnic groups than others.

Pathology Lesions 1-The name multiple sclerosis refers to the scars, better known as plaques or lesions that form in the nervous system.

2-These lesions most commonly affect the white matter in the optic nerve, brain stem, basal ganglia and spinal cord, or white matter tracts close to the lateral ventricles.

Periventricular Juxtacortical Infratentorial Spinal cord

3- The function of white matter cells is to carry signals between grey matter areas, where the processing is done. 4-The peripheral nervous system is rarely involved.

DIAGNOSIS of MS 1-Multiple sclerosis is typically diagnosed based on the presenting signs and symptoms, in combination with supporting medical imaging and laboratory testing.  

2-It can be difficult to confirm, especially early on, since the signs and symptoms may be similar to those of other medical problems.

3- The McDonald criteria, which focus on Clinical ,laboratory, and radiologic evidence of lesions at different times and in different areas, is the most commonly used method of diagnosis .

bands of IgG \\on electrophoresis, which are 4-The cerebrospinal fluid is tested for oligoclonal bands of IgG \\on electrophoresis, which are inflammation markers found in 75–85% of people with MS. 

5-The nervous system in MS may respond less actively to stimulation of the optic nerve and sensory nerves due to demyelination of such pathways. These brain responses can be examined using visual and sensory- evoked potentials.

TREATMENT. Acute attacks 1-During symptomatic attacks, administration of high doses 500-1000 mg of intravenous corticosteroids such as methylprednisolone, is the usual therapy for 3-5d,

1-Optimal treatment response :complete return to the pre-relapse level of functioning. 2-lack of complete recovery warrant consideration of expeditious use of a second-line relapse therapy. 1

3-Plasma exchange (every other day for at least 5 exchanges ), cyclophosphamide, intravenous immunoglobulin (IVIg),

Disease-modifying treatment. Relapsing remitting multiple sclerosis disease-modifying treatments have been approved by regulatory agencies for relapsing-remitting multiple sclerosis (RRMS) including: ,beta and 1a interferon Mitoxantrone , fingolimid.   

low-dose interferon beta-1a (IM weekly). High dose interferon beta-1a (subcutaneous 3 times a week). Interferon beta-1b (subcutaneous every other day).

ORAL AGENTS Fingolimod

1-sphingosine-1- phosphate receptor (S1P1) modulator and has immunoregulatory features. 2-inhibits the migration of T cells from lymphoid tissue into the peripheral circulation and target organs, including the CNS. 0.5 mg/day .

Side effects. 1-first-dose bradycardia, the possible risk of herpes virus dissemination, macular edema, long-term consequences of elevated blood pressure. 6-hour first-dose observation (FDO) includes hourly vital signs as well as an ECG before treatment and at the end of the 6-hour observation period.

2-Treatment of clinically isolated syndrome (CIS) with interferon decreases the chance of progressing to clinical MS.

Associated symptoms treatment 1-Both medications and neuro-rehabiltation have been shown to improve some symptoms, though neither changes the course of the disease.

2-Some symptoms have a good response to medication, such as an unstable bladder and spasticity, while others are little changed.