CLINICAL IMMUNOLOGY
MULTIPLE SCLEROSIS: CLINIC AND T REATMENT 1-11-2023
MS definition: multiple scars in the nervous system
Multifocal inflammation in the brain and spinal cord, can occur both in white or grey matter
Some facts about MS
- prevalence 1:1000 in NL
- starts between 20-40 years
- 1: 2/3 men to women ratio
- almost normal life expectancy
- prevalence increases with higher latitude
Contributing factors:
- vitamin D levels
- diet
- smoking
- Epstein-Barr virus/mononucleosis infectiosa
- ethnicity
- genes
Anatomy
- grey matter
cell bodies of neurons
- white matter
axons
surrounded by myelin
- myelin improves conduction of axons (more efficient neuronal signalling)
- myelin is built by oligodendrocytes
Pathophysiology
‘chronic inflammatory demyelinating disease of the central nervous system’
pathological hallmarks:
- inflammation
- demyelination
- remyelination
- gliosis (scarring)
Inflammation and demyelination of the CNS
inflammation
- blood brain barrier becomes more leaky
- immune cells enter the brain
demyelination
- conduction slows down
T cells (CD8 & CD4) and B cells (CD20) secrete cytokines and antibodies which cross the blood-brain barrier and
enter the CNS, where damage is caused to the tissue
,Normal white matter:
- axons (red) are surrounded by myelin (green), black parts are blood vessels
In MS, active lesion:
- immune cells accumulate
Chronic active lesion:
- ring formation of immune cells along the outer edge, axons are not surrounded by myelin anymore
Gliosis/scar formation:
- fibrosis, remyelination is not possible anymore due to the scarring of the tissue
Remyelination and scarring
- remyelination
oligodendrocytes
full or partial recovery
- gliosis
, scarring
→ repeating cycles
Clinical features of MS:
- vary widely
different locations
different severity
- new neurological symptoms – relapses
slow progressive symptoms (hours to days)
lasting >24 hours
not attributable to other causes than MS
Example of a clinical case: female, 25 yr
- slow progressive weakness left leg, 2 weeks, now stable
- history/migraine
- NO / paresis left leg, increased reflexes left leg
- could this be MS?
Diagnosing MS
- clinical features
- radiological characteristics
- abnormalities in CSF
Diagnosis based on:
- dissemination in time (DIT) – there needs to be multiple occurrences of disease over time
- dissemination in space (DIS) – lesions have to occur in multiple places
Symptoms:
- visual problems
optic neuritis – pain behind the eye, decreased colour vision, decreased visual acquity,
especially central visual fields
double vision, = diplopia
- pyramidal symptoms
paresis
spasticity
abnormal reflexes
- sensory disturbances
tingling/painful sensations
numbness
symptom of Lhermitte = tingling sensation in the hands and feet when the individual bends their
head forwards
- bladder-/bowel-/sexual problems
incontinence – urine, faeces
urine retention
frequent urinary tract infections
sexual problems
- coordination problems
ataxia
tremor
balance
- cognitive disturbances
memory
, concentration
attention
difficulty organising
- fatigue
high prevalence
no good treatment
unknown cause
less visible
Less visible symptoms a person can have:
- depression
50% have an episode during disease course
- suicide
7-8 times more frequent
- can affect the relationship
24 yrs after diagnosis 33% same relationship vs 53% of the general population (Denmark)
- walk independently
50% after 25 years
MRI in MS
- lesions in the brain and spinal cord
- number, size and distribution vary widely
- typical MS lesions
ovoid shaped
perivascular orientation
T2 lesions: disease burden
T1 lesions: black holes, irreversible damage
T1 contrast: enhancing lesions → active lesions
MULTIPLE SCLEROSIS: CLINIC AND T REATMENT 1-11-2023
MS definition: multiple scars in the nervous system
Multifocal inflammation in the brain and spinal cord, can occur both in white or grey matter
Some facts about MS
- prevalence 1:1000 in NL
- starts between 20-40 years
- 1: 2/3 men to women ratio
- almost normal life expectancy
- prevalence increases with higher latitude
Contributing factors:
- vitamin D levels
- diet
- smoking
- Epstein-Barr virus/mononucleosis infectiosa
- ethnicity
- genes
Anatomy
- grey matter
cell bodies of neurons
- white matter
axons
surrounded by myelin
- myelin improves conduction of axons (more efficient neuronal signalling)
- myelin is built by oligodendrocytes
Pathophysiology
‘chronic inflammatory demyelinating disease of the central nervous system’
pathological hallmarks:
- inflammation
- demyelination
- remyelination
- gliosis (scarring)
Inflammation and demyelination of the CNS
inflammation
- blood brain barrier becomes more leaky
- immune cells enter the brain
demyelination
- conduction slows down
T cells (CD8 & CD4) and B cells (CD20) secrete cytokines and antibodies which cross the blood-brain barrier and
enter the CNS, where damage is caused to the tissue
,Normal white matter:
- axons (red) are surrounded by myelin (green), black parts are blood vessels
In MS, active lesion:
- immune cells accumulate
Chronic active lesion:
- ring formation of immune cells along the outer edge, axons are not surrounded by myelin anymore
Gliosis/scar formation:
- fibrosis, remyelination is not possible anymore due to the scarring of the tissue
Remyelination and scarring
- remyelination
oligodendrocytes
full or partial recovery
- gliosis
, scarring
→ repeating cycles
Clinical features of MS:
- vary widely
different locations
different severity
- new neurological symptoms – relapses
slow progressive symptoms (hours to days)
lasting >24 hours
not attributable to other causes than MS
Example of a clinical case: female, 25 yr
- slow progressive weakness left leg, 2 weeks, now stable
- history/migraine
- NO / paresis left leg, increased reflexes left leg
- could this be MS?
Diagnosing MS
- clinical features
- radiological characteristics
- abnormalities in CSF
Diagnosis based on:
- dissemination in time (DIT) – there needs to be multiple occurrences of disease over time
- dissemination in space (DIS) – lesions have to occur in multiple places
Symptoms:
- visual problems
optic neuritis – pain behind the eye, decreased colour vision, decreased visual acquity,
especially central visual fields
double vision, = diplopia
- pyramidal symptoms
paresis
spasticity
abnormal reflexes
- sensory disturbances
tingling/painful sensations
numbness
symptom of Lhermitte = tingling sensation in the hands and feet when the individual bends their
head forwards
- bladder-/bowel-/sexual problems
incontinence – urine, faeces
urine retention
frequent urinary tract infections
sexual problems
- coordination problems
ataxia
tremor
balance
- cognitive disturbances
memory
, concentration
attention
difficulty organising
- fatigue
high prevalence
no good treatment
unknown cause
less visible
Less visible symptoms a person can have:
- depression
50% have an episode during disease course
- suicide
7-8 times more frequent
- can affect the relationship
24 yrs after diagnosis 33% same relationship vs 53% of the general population (Denmark)
- walk independently
50% after 25 years
MRI in MS
- lesions in the brain and spinal cord
- number, size and distribution vary widely
- typical MS lesions
ovoid shaped
perivascular orientation
T2 lesions: disease burden
T1 lesions: black holes, irreversible damage
T1 contrast: enhancing lesions → active lesions
