Clinical immunology
Lecture 1: Multiple sclerosis- clinic & treatment
1. Background
Definition: multiple scars in the central nervous system
Multifocal inflammation in the brain and spinal cord.
- White matter
- Gray matter
MS facts
- Prevalence 1:1000 in the NL
- Starts between 20-40 years
- More women are affected than man
- Almost normal life expectancy
- Prevalence increases with higher latitude → less sun → less Vit D
Contributing factors
- Vitamin D levels
- Diet
- Smoking
- Epstein-barr virus/mononucleosis infectiosa
- Ethnicity and genes
Anatomy
- Gray matter → cell bodies of the axons are located here
- White matter → axons surrounded by myelin
- Myelin → improves the conduction → action potential is disrupted because of the
lesions in the brains
- The myelin is build up by oligodendrocytes and are covered by myelin sheets
Pathological hallmarks: chronic inflammatory demyelinating disease of the CNS
→ inflammation, demyelination, remyelination, gliosis (scarring)
Inflammation and demyelination of the CNS
- The blood brain barrier (BBB) is infiltrated by immune cells, the immune cells cause a
immune response in the brain → the immune cells attack the myelin resulting in
lesions in the brain
- The immune cells in in the blood vessels in the white matter → later scaring is
Induced by the immune cells
Remyelination and scarring
- Remyelination: the myelin recovers fully or partially
- Gliosis is the scarring of the brain → the scar formation is formed after the damage of
the demyelination
- The cycle repeats itself
, 2. Clinical symptoms
Clinical features
- Symptoms in MS vary widely, it has different locations and severity
- New neurological symptoms, relapses → slowly progressive symptoms
Symptoms in MS
- Symptoms vary widely → different location and different severity
3. Diagnosis MS
Diagnosis
- Clinical features are checked if it is linked to MS
- Radiological characteristics
- Abnormalities in cerebrospinal fluid
- Diagnosis based on
o Dissemination of time (DIT) → new attacks or relapses
o Dissemination of space (DIS) → different places in your brain or spinal cord
that have been damaged
Symptoms
- Visual problems
o Pain behind the eye, decreased colour vision decreased, diplopia (double
vision)
- Pyramidal symptoms
o Paresis
o Spasticity
o Abnormal reflexes
- Sensory symptoms
o Tingling, Numbness
o Symptom of Lhermite
, - Bladder-/bowel/sexual problems
o Incontinence: urine and faeces
o Urine retention, frequent urinary tract infections, sexual problems
- Coordination problems
o Ataxia
o Tremor
o Balance
- Coordination problems
o Memory, concentration, attentions, difficulties organizing
- Fatique
o High prevalence and there is no good treatment for this
o Unknown cause of the fatique and its less visible
- Less visible
o Depression, suicide, relationship, walking gets difficult after a while
Clinical DIS/DIT
- The first phase the optic neuritis starts. In the second relapse gait problems strt, so a
wheelchair is needed. In the thirs relapse diplopia starts
MRI in MS
- With the MRI the lesions in the brain and in the spinal cor scan be visualized. The
number size and distribution vary widely
- Typical brain lesions are ovoid shaped and are close to the bloodvessels, because this
is the location where the immune cells infiltrate the brain → perivascular orientation
Different types of MRIs for different lesions
- T2 lesions → disease burden
- T1 lesions → black holes, irreversible damage
- T1 contrast → enhancing lesions, active lesions
Specific MS localization
- Specific locations for the lesions
o periventricular: close to the ventricles in the brain
o Juxtacortical: close to the cortex
o Infratentorial: above the cerebellum
o Spinal cord
- Dissemination in SPACE → lesions in 2 of 4 locations
- MRI show dissemination in time → make different MRIs
at different time points
o Combination of different type of lesions
o Combination of T2 lesions and contrast enhancing
lesions
o New T2 lesions over time
MRI in MS - degeneration
- Atrophy: widening of ventricles that happens in a later disease stage in both brain
and spinal cord
- Partially independent from white matter lesion load
- Exclusions of differential diagnosis
- Monitor the disease activity → to determine the efficacy of the treatment and
pharmacovigilance → medicine
, Cerebrospinal fluid (CSF)
- Used to determine the dissemination in time for MS patients
- Oligoclonal bands → extra clue for correct diagnosis of MS
o In MS patients there are a lot of thick IgG oligoclonal bands
o Done by a lumbar puncture
McDonald criteria
- For Dissemination in time and space for diagnosing the patient
Clinically isolated syndrome (CIS)
- Pre-symptoms of MS
- Monosymptomatic clinical presentation demyelination
- Could evolve to MS later
→ do a follow up to determine whether it evolves to MS
4. Disease course and subtypes
Different MS subtypes
- Relapsing-remitting (RRMS)
- Secondary progressive (SPMS)
- Primary progressive (PPS) → progressive
relapsing (PRMS)
Disease progression of MS
- Radiological isolated syndrome (RIS) > CIS
and MS
- Clinically isolated syndrome (CIS) → RRMs
and SPMS
Most common presenting symptoms
- Relapsing-remitting MS: optic
neuritis, sensory symptoms
- Primary progressive MS: motor
symptoms, progressive walking
disabilities
Lecture 1: Multiple sclerosis- clinic & treatment
1. Background
Definition: multiple scars in the central nervous system
Multifocal inflammation in the brain and spinal cord.
- White matter
- Gray matter
MS facts
- Prevalence 1:1000 in the NL
- Starts between 20-40 years
- More women are affected than man
- Almost normal life expectancy
- Prevalence increases with higher latitude → less sun → less Vit D
Contributing factors
- Vitamin D levels
- Diet
- Smoking
- Epstein-barr virus/mononucleosis infectiosa
- Ethnicity and genes
Anatomy
- Gray matter → cell bodies of the axons are located here
- White matter → axons surrounded by myelin
- Myelin → improves the conduction → action potential is disrupted because of the
lesions in the brains
- The myelin is build up by oligodendrocytes and are covered by myelin sheets
Pathological hallmarks: chronic inflammatory demyelinating disease of the CNS
→ inflammation, demyelination, remyelination, gliosis (scarring)
Inflammation and demyelination of the CNS
- The blood brain barrier (BBB) is infiltrated by immune cells, the immune cells cause a
immune response in the brain → the immune cells attack the myelin resulting in
lesions in the brain
- The immune cells in in the blood vessels in the white matter → later scaring is
Induced by the immune cells
Remyelination and scarring
- Remyelination: the myelin recovers fully or partially
- Gliosis is the scarring of the brain → the scar formation is formed after the damage of
the demyelination
- The cycle repeats itself
, 2. Clinical symptoms
Clinical features
- Symptoms in MS vary widely, it has different locations and severity
- New neurological symptoms, relapses → slowly progressive symptoms
Symptoms in MS
- Symptoms vary widely → different location and different severity
3. Diagnosis MS
Diagnosis
- Clinical features are checked if it is linked to MS
- Radiological characteristics
- Abnormalities in cerebrospinal fluid
- Diagnosis based on
o Dissemination of time (DIT) → new attacks or relapses
o Dissemination of space (DIS) → different places in your brain or spinal cord
that have been damaged
Symptoms
- Visual problems
o Pain behind the eye, decreased colour vision decreased, diplopia (double
vision)
- Pyramidal symptoms
o Paresis
o Spasticity
o Abnormal reflexes
- Sensory symptoms
o Tingling, Numbness
o Symptom of Lhermite
, - Bladder-/bowel/sexual problems
o Incontinence: urine and faeces
o Urine retention, frequent urinary tract infections, sexual problems
- Coordination problems
o Ataxia
o Tremor
o Balance
- Coordination problems
o Memory, concentration, attentions, difficulties organizing
- Fatique
o High prevalence and there is no good treatment for this
o Unknown cause of the fatique and its less visible
- Less visible
o Depression, suicide, relationship, walking gets difficult after a while
Clinical DIS/DIT
- The first phase the optic neuritis starts. In the second relapse gait problems strt, so a
wheelchair is needed. In the thirs relapse diplopia starts
MRI in MS
- With the MRI the lesions in the brain and in the spinal cor scan be visualized. The
number size and distribution vary widely
- Typical brain lesions are ovoid shaped and are close to the bloodvessels, because this
is the location where the immune cells infiltrate the brain → perivascular orientation
Different types of MRIs for different lesions
- T2 lesions → disease burden
- T1 lesions → black holes, irreversible damage
- T1 contrast → enhancing lesions, active lesions
Specific MS localization
- Specific locations for the lesions
o periventricular: close to the ventricles in the brain
o Juxtacortical: close to the cortex
o Infratentorial: above the cerebellum
o Spinal cord
- Dissemination in SPACE → lesions in 2 of 4 locations
- MRI show dissemination in time → make different MRIs
at different time points
o Combination of different type of lesions
o Combination of T2 lesions and contrast enhancing
lesions
o New T2 lesions over time
MRI in MS - degeneration
- Atrophy: widening of ventricles that happens in a later disease stage in both brain
and spinal cord
- Partially independent from white matter lesion load
- Exclusions of differential diagnosis
- Monitor the disease activity → to determine the efficacy of the treatment and
pharmacovigilance → medicine
, Cerebrospinal fluid (CSF)
- Used to determine the dissemination in time for MS patients
- Oligoclonal bands → extra clue for correct diagnosis of MS
o In MS patients there are a lot of thick IgG oligoclonal bands
o Done by a lumbar puncture
McDonald criteria
- For Dissemination in time and space for diagnosing the patient
Clinically isolated syndrome (CIS)
- Pre-symptoms of MS
- Monosymptomatic clinical presentation demyelination
- Could evolve to MS later
→ do a follow up to determine whether it evolves to MS
4. Disease course and subtypes
Different MS subtypes
- Relapsing-remitting (RRMS)
- Secondary progressive (SPMS)
- Primary progressive (PPS) → progressive
relapsing (PRMS)
Disease progression of MS
- Radiological isolated syndrome (RIS) > CIS
and MS
- Clinically isolated syndrome (CIS) → RRMs
and SPMS
Most common presenting symptoms
- Relapsing-remitting MS: optic
neuritis, sensory symptoms
- Primary progressive MS: motor
symptoms, progressive walking
disabilities
