Clinical immunology HC1 – MS an overview of clinical aspects
Epidemiology
More women affected than men
Pathology
Disease of CNS: brain + spinalcord
Demyelination:
- B- & T-cells break down myelin (inflammatory process) → lesions
- These lesions are typically shown on MRI and have preferential localisations in the brain
Typical places of lesions in MS:
1. Perifrenticular
2. Below cortex
3. Infratentorium (?)
4. Spinalcord
Degeneration:
- Neuronal loss of chronically
demyelinated axons
- Damage
- Gliosis of astrocytes
- Activated microglia (?)
Cause
Not a genetic disease, but a familial disease
→ Higher risk when it’s in the family but not a specific gene that is passed on
Environmental factors:
- Virus (EBV)
- Vitamin D → low vitamin D = higher risk of MS
- Smoking Also have interactions with the genes that are identified
- Early obesisty with higher risk in MS
,Symptoms
- Optic neuritis (70% of MS patients)
• Blurry vision in 1 eye
• Pain behind this eye
• Loss of colour vision
- Eye movements
• Diplopia (double vision)
- Lhermitte’s symptom → lesions in cervical spine
• Flex neck → gives electrical sensation down the back
- Loss of motor function
- Bladder dysfunction
• Lesion in spinal cord
- Psychological functions (in 45-65%)
• Slowing of processing
• Attention deficit
• Disturbances of memory
• Disturbances of language functions
- Fatigue (most common)
• Super tired
• Cause unknown
Diagnosis
3 different courses of MS
1. RRMS: Relapsing Remitting MS
• Inflammation
• Relapses mainly in the beginning
2. PPMS: Primary Progressive MS
• More about degeneration, not so much inflammation
• Small group of MS (need to be progressive for over a year to get the diagnosis)
• Steady increase in disability without attacks
3. SPMS: Secondary Progressive MS
• Relapses disappear
• Degeneration
,Diagnosis
- Dissemination in space
- Dissemination in time
• >1 relapses
• MRI
▪ New lesions on follow-up MRI
▪ New/active = contrast enhancing lesion
At the same time
▪ Old = non-contrast enhancing lesion
• Presence of oligoclonal bands (inflammatory protein) in cerebrospinal fluid (CSF)
Clinically isolated syndrome (CIS) = maar 1 relapse of lesions, zitten maar op 1 plek (nog geen MS)
Radiological isolated syndrome (RIS) = no symptoms, maar MRI shows lesions (nog geen MS)
, Follow up:
- Clinical
- MRI
- Biochemical
Neurofillament light = most important biomarker
→ High in active MS
Clinical immunology HC2 – MS and therapy
Clinical and MRI disease activity throughout the course of MS:
Targets for MS drugs: mostly immune modulating
1995 first (treatment) drug: interferon β-1b
Early therapy is important to delay the accumulation of irreversible neurologic damage and
consequent disability
Ocrelizumab is the only drug for PPMS
MS disease modifying therapies (DMTs):
- First line
• Interferon β (Avonex, Rebif, Betaferon, Plegridy)
• Glatiramer acetate (Copaxone, generic)
• Teriflunomide (Aubagio)
• Dimethylfumarate (Tecfidera)
- Second line
• Natalizumab (Tysabri)
• Fingolimod (Gilenya)
• Alemtuzumab (Lemtrada)
• Ocrelizumab (Ocrevus)
• Cladribine (Mavenclad)
Most of second line treatments are monoclonal
Epidemiology
More women affected than men
Pathology
Disease of CNS: brain + spinalcord
Demyelination:
- B- & T-cells break down myelin (inflammatory process) → lesions
- These lesions are typically shown on MRI and have preferential localisations in the brain
Typical places of lesions in MS:
1. Perifrenticular
2. Below cortex
3. Infratentorium (?)
4. Spinalcord
Degeneration:
- Neuronal loss of chronically
demyelinated axons
- Damage
- Gliosis of astrocytes
- Activated microglia (?)
Cause
Not a genetic disease, but a familial disease
→ Higher risk when it’s in the family but not a specific gene that is passed on
Environmental factors:
- Virus (EBV)
- Vitamin D → low vitamin D = higher risk of MS
- Smoking Also have interactions with the genes that are identified
- Early obesisty with higher risk in MS
,Symptoms
- Optic neuritis (70% of MS patients)
• Blurry vision in 1 eye
• Pain behind this eye
• Loss of colour vision
- Eye movements
• Diplopia (double vision)
- Lhermitte’s symptom → lesions in cervical spine
• Flex neck → gives electrical sensation down the back
- Loss of motor function
- Bladder dysfunction
• Lesion in spinal cord
- Psychological functions (in 45-65%)
• Slowing of processing
• Attention deficit
• Disturbances of memory
• Disturbances of language functions
- Fatigue (most common)
• Super tired
• Cause unknown
Diagnosis
3 different courses of MS
1. RRMS: Relapsing Remitting MS
• Inflammation
• Relapses mainly in the beginning
2. PPMS: Primary Progressive MS
• More about degeneration, not so much inflammation
• Small group of MS (need to be progressive for over a year to get the diagnosis)
• Steady increase in disability without attacks
3. SPMS: Secondary Progressive MS
• Relapses disappear
• Degeneration
,Diagnosis
- Dissemination in space
- Dissemination in time
• >1 relapses
• MRI
▪ New lesions on follow-up MRI
▪ New/active = contrast enhancing lesion
At the same time
▪ Old = non-contrast enhancing lesion
• Presence of oligoclonal bands (inflammatory protein) in cerebrospinal fluid (CSF)
Clinically isolated syndrome (CIS) = maar 1 relapse of lesions, zitten maar op 1 plek (nog geen MS)
Radiological isolated syndrome (RIS) = no symptoms, maar MRI shows lesions (nog geen MS)
, Follow up:
- Clinical
- MRI
- Biochemical
Neurofillament light = most important biomarker
→ High in active MS
Clinical immunology HC2 – MS and therapy
Clinical and MRI disease activity throughout the course of MS:
Targets for MS drugs: mostly immune modulating
1995 first (treatment) drug: interferon β-1b
Early therapy is important to delay the accumulation of irreversible neurologic damage and
consequent disability
Ocrelizumab is the only drug for PPMS
MS disease modifying therapies (DMTs):
- First line
• Interferon β (Avonex, Rebif, Betaferon, Plegridy)
• Glatiramer acetate (Copaxone, generic)
• Teriflunomide (Aubagio)
• Dimethylfumarate (Tecfidera)
- Second line
• Natalizumab (Tysabri)
• Fingolimod (Gilenya)
• Alemtuzumab (Lemtrada)
• Ocrelizumab (Ocrevus)
• Cladribine (Mavenclad)
Most of second line treatments are monoclonal
