references:
Phases and Phenotypes of Multiple Sclerosis By Orhun H. Kantarci, MD.
Diagnosis of Multiple Sclerosis By Jiwon Oh, MD, PhD, FRCPC
Nature Reviews | Disease Primers
Multiple sclerosis Massimo Filippi1,2*, Amit Bar- Or3, Fredrik Piehl4,5,6, Paolo Preziosa1,2, Alessandra Solari7, Sandra Vukusic8 and Maria A. Rocca1,2
EEG Maturation - Serial evolution of changes from Birth to Old AgeRahul Kumar
This presentation discusses in detail the evolution of the EEG patterns in the human brain, as the brain develops and matures. The sequence of changes as well as the shifting patterns coinciding with Myelination are discussed.
Multiple sclerosis: Introduction, Risk Factors, Diagnosis and TreatmentEnriqueAlvarez93
Introduction about Multiple Sclerosis.
Risk factors affect to Multiple Sclerosis.
When to Suspect Multiple Sclerosis.
Evaluation and Diagnosis of Multiple Sclerosis.
How to treatment of Multiple Sclerosis.
Treatment of Multiple Sclerosis with Monoclonal Antibody.
This presentation is an introduction to the principles of Nerve Conduction Study and is entirely sourced from the book by David C Preston and Barbara E Shapiro: Electromyography and Neuromuscular disorders, 3rd Edition
EEG Maturation - Serial evolution of changes from Birth to Old AgeRahul Kumar
This presentation discusses in detail the evolution of the EEG patterns in the human brain, as the brain develops and matures. The sequence of changes as well as the shifting patterns coinciding with Myelination are discussed.
Multiple sclerosis: Introduction, Risk Factors, Diagnosis and TreatmentEnriqueAlvarez93
Introduction about Multiple Sclerosis.
Risk factors affect to Multiple Sclerosis.
When to Suspect Multiple Sclerosis.
Evaluation and Diagnosis of Multiple Sclerosis.
How to treatment of Multiple Sclerosis.
Treatment of Multiple Sclerosis with Monoclonal Antibody.
This presentation is an introduction to the principles of Nerve Conduction Study and is entirely sourced from the book by David C Preston and Barbara E Shapiro: Electromyography and Neuromuscular disorders, 3rd Edition
A brief description about Demyelination topics by Dr Sabu Augustine for MBBS Students in Medical school.
References from textbooks and other presentations.
a presentation on autoimmune encephalitis, paraneoplastic syndrome. their types and various imaging and lab finding
their differential diagnosis
acute and long term management plans
Neuromyelitis optica spectrum disorders (NMOSD) is an autoimmune disorder of young adults' results from astrocytic aquaporin–4 (AQP–4) channelopathy. The AQP–4 IgG antibodies may be present in the context of some paraneoplastic disorders which should be suspected when NMOSD occurs in elderly patients.
main references:
-Epidemiology and
Pathophysiology of
Multiple Sclerosis
By Melanie Ward, MD; Myla D. Goldman, MD, MSc, FAAN
-Multiple sclerosis, Nature disease primer
Massimo Filippi1,2*, Amit Bar- Or3, Fredrik Piehl4,5,6, Paolo Preziosa1,2, Alessandra Solari7,
Sandra Vukusic8 and Maria A. Rocca1,2
references:
1-European Academy of Neurology/Peripheral Nerve Society guideline on diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy: Report of a joint Task Force—Second revision.
2-Chronic Inflammatory Demyelinating Polyradiculoneuropathy and Its Variants By Kelly Gwathmey, MD
3-Patient Journey in CIDP: Burden, Symptoms, and Diagnosis Jeffrey A. Allen, MD; Richard A. Lewis, MD
Neurological examination lec 1 vision and ocular systemLobna A.Mohamed
functional anatomy of the ocular system including ON,EOM and 3,4,6 CN
examination and signs of affection
differential diagnosis of poly CN and Optic neuropathy
Neurobiology of Alzheimer’s disease
Role of Acetyl choline
Amyloid-beta-mediated neurodegeneration
Amyloid beta accumulation
Amyloid cascade hypothesis
Microtubule-associated protein tau
Oxidative stress
ROS-mediated neuronal damage
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
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These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
4. 4
Optic nerve Spinal cord
Brainstem Cerebellum
Cerebral
hemisphere
Typically, the onset of MS is
characterized by an initial
clinical attack (defined as CIS)
in ~85% of patients, which
consists of an unpredictable
episode of neurological
dysfunction owing to
demyelinating lesions in the
CNS.
5. CLINICAL RELAPSE
An episode that lasts for ≥24 hours and occur in the absence of fever,
infection or clinical features of encephalopathy (for example, altered
consciousness or epileptic
seizures).
5
Symptoms of a clinical relapse typically show an acute or sub-acute onset,
worsen over days or weeks, reach a peak severity within 2–3 weeks and
remit to a variable degree.
Remission refers to the recovery phase, with some level of restoration of myelin
and axonal integrity. Maximum clinical recovery after a relapse generally
stabilizes within the first 3months and rarely continues beyond 6 months
following a relapse.
6. ASYMPTOMATIC
RELAPSE
Presents as subclinical
activity (new MRI lesions)
without symptoms.
6
Recovery in MRI lesions (symptomatic or
asymptomatic) can be defined as
resolution of enhancement, restoration
of diffusion characteristics, and
shrinkage in size of the MS lesion(s) on
MRI.
It is a recurrence of symptoms from a previous clinical
relapse or a subclinical lesion, likely indicates incomplete
recovery from the previous CNS insult.
Any stress to the CNS (eg, heat, infection, exercise, fatigue)
exceeding a threshold that the damaged CNS can sustain can
trigger a pseudorelapse.
If symptoms attributed to a pseudorelapse exceed the
arbitrary cutoff of 24 hours or do not start improving within
a few days despite identifying and intervening with a
potential trigger (eg, treatment of a urinary tract infection), an
MRI should be obtained to differentiate it from a symptomatic
relapse recurrent in the same location or close vicinity on the
same neural pathway.
PSEUDO
RELAPSE
7. 7
• Optic neuritis is the first neurological episode in
~25% of patients.
• During fundus oculi examination, the optic nerve
head appears normal if inflammation is limited to the
retrobulbar portion of the nerve, but approximately
one-third of patients might have inflammation of the
optic disc (papillitis) and disc oedema owing to
anterior optic neuritis.
• Patients without visual complaints with suspected MS
should be evaluated for more subtle manifestations
of optic neuritis, such as an afferent pupillary
defect or abnormalities at paraclinical tests (for
example, visual evoked potentials, optical OCT or
MRI).
Partial or total visual loss in
one eye.
Central scotoma (a blind spot
in the visual field).
Dyschromatopsia (deficiency
of colour vision).
Pain within the orbit that is
worsened by eye movement.
Optic neuritis
8. 8
• Sensory symptoms are the first clinical
manifestation in up to 43% of patients with MS and
are mainly caused by myelitis or brainstem
syndromes.
• Sensory symptoms can temporarily worsen with
increased body temperature (known as Uhthoff
phenomenon).
Paresthesia (commonly described
as numbness, tingling, pins-and-
needles feeling, tightness,
coldness and/or swelling of the
limbs or trunk).
Lhermitte sign(a transient
symptom described as an electric
shock radiating down the spine or
into the limbs with flexion of the
neck).
Impairment of vibration and joint
position sensation, and reduced
pain and light touch perception.
Sensory
symptoms
9. 9
• Motor manifestations are the initial symptoms in 30–
40% of patients and affect almost all patients during
the course of the disease.
Pyramidal signs (such as
Babinski sign, more
pronounced reflexes and
clonus).
Paresis.
Spasticity.
Motor
symptoms
10. 10
• Brainstem and cerebellar symptoms are present in
up to 70% of patients with MS.
Nystagmus.
Oscillopsia.
Diplopia.
Ataxia and gait imbalance.
Decomposition of
movements.
Dysarthria and dysphagia.
Infratentorial
symptoms
11. 11
Sphincteric and
sexual
dysfunction
The extent of sphincter and sexual dysfunction often parallels the degree of motor
impairment in the lower extremities, and the dysfunction usually becomes permanent
late in the disease course, affecting 34–99% of patients.
The most common symptom of bladder dysfunction is urinary urgency, but
hesitancy, frequency and urge incontinence can also occur.
Constipation is more common than faecal incontinence, and men with MS often have
erectile dysfunction and impotence.
12. 12
Cognitive
symptoms
Overall, 40–70% of patients with MS have cognitive impairment, which can
start in the earliest phases of the disease.
Cognitive deficits can predict conversion to clinically definite MS in patients
with CIS, are more frequent and more pronounced in chronic progressive MS,
worsen over time and affect patients’ daily life activities.
Common cognitive symptoms include impairment in information processing
speed, episodic memory, attention, efficiency of information processing and
executive function.
13. 13
Fatigue
Fatigue can be associated with relapses and can persist after the attack has
subsided, but it can also be a feature of daily life and can be present for years.
Several strings of evidence support the hypothesis of a central origin of MS-related
fatigue owing to a dysfunction of cortico-subcortical circuits, mainly involving
structural damage in fronto-parietal regions and the basal ganglia.
Sleep disorders (for example, insomnia, obstructive sleep apnea and restless legs
syndrome) are found in up to 54% of patients with MS and might also promote fatigue.
14. 14
Other symptoms
Affective disturbance occurs in up to two-thirds of patients, of which depression is the
most common manifestation.
Pain is reported in up to 43% of patients and can include trigeminal neuralgia,
dysesthetic pain, back pain, visceral pain and painful tonic spasms.
16. RRMS
Schumacher
1965
• Typical MS-related demyelination.
• Objective evidence of CNS involvement.
• Dissemination in time.
• Dissemination in space.
• No better explanation.
16
Typical syndromes: optic
neuritis,
brainstem syndromes such as
internuclear ophthalmoplegia and
trigeminal neuralgia, cerebellar
syndromes, and transverse
myelitis.
Objective evidence: clinical, paraclinical,
or radiographic evidence of a corroborating
CNS lesion that would explain the
presenting symptoms.
Dissemination in space is defined as detection of
lesions in more than one distinct anatomic location
within the CNS. Multifocal CNS involvement is
characteristic of MS.
Dissemination in time requires confirmation
of new CNS lesions over time, suggesting an
ongoing disease process typical of MS rather than
a monophasic disease.
18. 18
McDonald’s
criteria
2017
Role of MRI in diagnosis of multiple sclerosis
• Brain and spinal cord MRI remain the most useful paraclinical tests to aid
the diagnosis of MS and can substitute for clinical findings in the of DIS
or DIT in patients with a typical CIS.
• There was general agreement that, although spinal MRI is not mandatory
in all cases, it is advisable when:
The presentation suggests a spinal cord localization.
There is a primary progressive course.
Considering MS in a population in which the disease is less common (eg,
older individuals or non-white populations).
Additional data are needed to increase diagnostic confidence (eg, when brain
MRI findings only just fulfil the criteria for DIS).
• Spinal MRI seems to be less useful in the diagnosis of MS in children
than in adults.
21. 21
McDonald’s
criteria
2017
Role of CSF in diagnosis of multiple sclerosis
• The qualitative demonstration of two or more CSF specific oligoclonal bands
more reliably indicates intrathecal antibody synthesis than do other tests,
such as the IgG index.
• The sensitivity of oligoclonal band testing depends on the method used;
agarose gel electrophoresis with isoelectric focusing and immunoblotting or
immunofixation for IgG is the most sensitive approach at present.
• Importantly, analysis of paired CSF and serum samples is essential to
confirm that the oligoclonal bands are unique to CSF.
• The threshold for CSF examination should be low to increase diagnostic
confidence.
• CSF oligoclonal bands are not specific for MS and its absence don’t exclude
the diagnosis of MS.
22. 22
• CSF examination is strongly recommended in the
following situations:
when clinical and MRI evidence is insufficient to support a diagnosis of MS
particularly if initiation of DMT is being considered.
When there is a presentation other than a typical CIS, including a progressive
course at onset PPMS.
When clinical, imaging, or laboratory features are atypical of MS.
In populations in which MS is less common (eg, children, older individuals, or
non-white populations).
24. 24
Cortical MRI
lesions
• Lesions within the cerebral cortex.
• Typically, special MRI techniques such as
DIR, phase-sensitive
• inversion recovery, and magnetisation-
prepared rapid acquisition with gradient
echo sequences are required to visualise
these lesions.
• The lesions detected by these techniques
are primarily of the leukocortical type;
subpial lesions are rarely detected.
• Care is needed to distinguish potential
cortical lesions from neuroimaging
artefacts.
• A T2-hyperintense
cerebral white matter
lesion abutting the cortex,
and not separated from it
by white matter.
Juxtacortical
MRI lesions
Peri -
ventricular
lesions
• A T2-hyperintense cerebral
white matter lesion abutting
the lateral ventricles without
white matter in between,
including lesions in the
corpus callosum but
excluding lesions in deep
grey matter structures.
25. 25
Original development of the
McDonald criteria and
subsequent revisions were
largely based on data from
adult white European and
North American populations
with a typical clinically
isolated syndrome and age
younger than 50 years.
The application of McDonald
criteria alone for diagnosis of
MS in patients with atypical
clinical presentations is not
recommended and further
clinical, laboratory, and
radiologic assessments
beyond the minimum
requirements of the McDonald
criteria are necessary to
confirm a
diagnosis of MS.
Criteria critique
The criteria are generally
most applicable to patients
who are 11 years of age or
older; special care is needed
in patients younger than
11 years old, in whom the
likelihood of multiple sclerosis
is lower.
26. PPMS 26
• The diagnostic criteria for primary progressive multiple sclerosis remain the same in
the 2017 McDonald criteria as those outlined in the 2010 McDonald criteria.
• The 2013 revised classification of the clinical phenotypes and disease course of MS
maintained the distinction between MS with an attack onset versus a progressive
course from onset.
• The revised classification incorporated further categorization as active or not
(based on recent clinical relapse or MRI lesion activity) and progressive or not
(based on clinical assessment of disability).
28. Radiologically isolated syndrome
(RIS)
28
Individuals with RIS have a high likelihood of having MS
and might already exhibit evidence of putative
pathobiology, including fatigue, cognitive impairment, or
thalamic atrophy, and that postponing the diagnosis of MS
and initiation of DMT might increase the risk of disability.
Misdiagnosis is high in patients with MRI abnormalities
only, and that two-thirds of these patients will not receive
a diagnosis of multiple sclerosis within 5 years.
29. 29
McDonald’s
criteria
2017
The Panel reached a consensus to continue to require
clinical manifestations to make the diagnosis of MS and, as
in the 2010 McDonald criteria, to allow the use of historical
radiological evidence for DIS and DIT in patients with RIS
to support the diagnosis of MS once a typical CIS occurs.
Factors that increase the likelihood of patients with RIS
converting to MS based on retrospective studies include:
Male sex.
Age younger than 37 years.
Presence of spinal cord lesions.
Infratentorial lesions.
CSF-specific OCB.
The development of gadolinium-enhancing lesions on follow-
up MRI.
30. 30
Okuda DT, Mowry EM, Beheshtian A, et al.
Incidental MRI anomalies suggestive of
multiple
sclerosis: the radiologically isolated syndrome.
Neurology 2009;72(9):800-805. doi:10.1212/01.
wnl.0000335764.14513.1a
31. Solitary
sclerosis
31
Possible MS
McDonald’s
criteria
2017
Patients who have an inflammatory lesion of the cerebral white
matter, cervico-medullary junction, or spinal cord who develop
progressive disability that is clinically indistinguishable
from progressive forms of MS and who might have CSF-
specific OCB but have no clinical or radiological evidence of
new lesion formation. The Panel agreed that despite a
progressive
course, such patients do not satisfy the McDonald criteria
for MS , because they do not have DIS.
The 2010 McDonald criteria5 include a diagnostic category of
possible MS, defined as a suspicion of MS (ie, a patient with a
CIS but not meeting the full criteria). The Panel considered
expanding the category of possible MS to include patients with
atypical presentations, but did not reach a consensus.
37. 37
Current disease
course
classification in MS
Progression
Relapses
Interaction between two phenomena,
relapses and progression, describe
the disease course in MS. These
phenomena can overlap at different
stages in the disease.
MS high risk
phase
RR phase
Progressive
phase
Each phase is further defined as
active or inactive at any given
time.
40. 40
Progression
Insidious and
irreversible
worsening of
neurologic
function due to
MS over years.
Pseudo-
progression
Accumulating
insidious
disability due to
factors
indirectly
related or
unrelated to MS
Worsening
disability
Worsening disability can be due to:
• The stepwise accumulation of neurologic deficit from
partially recovered relapses.
• The insidious accumulation of neurologic deficit from
progressive disease course.
• A combination of both, or other MS or non–MS-related
factors
42. 42
Onset of the progressive phase of MS
seemingly is age dependent but
agnostic for disease duration and pre-
progressive
phase.
Once the progressive phase starts, the relapse-based
disability accumulation gives secondary progressive MS
and single-attack progressive MS a head start over
primary progressive MS at the time of progressive MS
onset leading to a higher starting point of disability.
DMT are efficacious early in MS, but the utility of
continuing them in patients older than age 60 should be
considered on an individual basis.
50. 50
The segment of optic nerve involvement is usually short, unilateral and confined to the optic nerve
itself.
T1 post contrast Left
T1 Coronal Left T2 axial Left
55. CENTRAL VEIN SIGN
• When appropriate susceptibility-based MRI sequences are used, it is often possible to visualize
central veins within white matter lesions, which are thought to be suggestive of lesions that have
formed due to perivenular inflammation and demyelination, a pathologic hallmark of MS-related
lesions.
• Numerous studies have demonstrated that people with MS have a high proportion of white matter
lesions demonstrating the central vein sign.
55
The 40 % role
If more than 40 % of
white matter lesions
demonstrate the central
vein sign, the likelihood
of a diagnosis of MS is
quite high.
Select 3 Select 6
At least three lesions
have evidence of the
central vein sign on
specific MRI
sequences.
At least six lesions have
evidence of the central
vein sign on specific
MRI sequences.
Automated methods of central vein sign detection are also emerging.
56. 56
NAIMS
consensus
statment
The venocentric distribution of lesions exists in all MS clinical phenotypes
(RRMS, SPMS and PPMS).
When imaging is used to examine the proportion of MS lesions with a central vein,
the location of the lesion should be taken into account. Current evidence suggests
that the prevalence of central veins is highest in periventricular and deep white
matter lesions.
The effects of comorbidities (such as vascular conditions) on the proportion of
lesions with a central vein in patients with MS should not be neglected.
The available evidence from MRI studies indicates that in comparison to patients
with MS, individuals with AQP4-IgG-positive NMOSD, SAD (Behçet syndrome,
systemic lupus erythematosus and antiphospholipid syndrome), CSVD, Susac
syndrome and migraine have a significantly lower proportion of brain lesions
with a central vein.
SATI, Pascal, et al. The central vein sign and its clinical evaluation for the diagnosis of multiple sclerosis: a
consensus statement from the North American Imaging in Multiple Sclerosis Cooperative. Nature Reviews
Neurology, 2016, 12.12: 714-722.
58. 58
NAIMS
consensus
statement
Imaging of veins in the brain can be performed using T2*-based MRI
sequences at any magnetic field strength (1.5 T, 3 T or 7 T).
Although T2* imaging is most sensitive at 7 T, a high detection rate can still
be achieved at clinical field strengths (1.5 T and 3 T) with optimized
sequences.
Owing to the small dimensions of the central veins, images should be
acquired at the highest resolution possible. The use of submillimetre voxel
dimensions can be particularly helpful
High-resolution isotropic T2*with 3D EPI is currently the most
promising acquisition to adequately detect central veins while preserving a
clinically compatible scan time.
SATI, Pascal, et al. The central vein sign and its clinical evaluation for the diagnosis of multiple sclerosis: a
consensus statement from the North American Imaging in Multiple Sclerosis Cooperative. Nature Reviews
Neurology, 2016, 12.12: 714-722.
59. 59
Examples of lesions with and without central veins.
a | Dawson’s finger-shaped lesion with a central vein running perpendicular to the sagittal plane.
b | Periventricular lesion with a hypointense rim located next to the atrium of the lateral ventricle.
c | Small finger-like lesion with a diameter slightly >3 mm in its short axis. The central vein is not as conspicuous as in previous examples, but it is still visible.
d | Small deep white matter lesion with diameter >3 mm and no visible central vein in any plane.
e | Small subcortical lesion with diameter >3 mm and no visible central vein in any plane.
f | Juxtacortical lesion with no visible central vein in any plane.
g | Small hyperintense area with diameter <3 mm located around a parenchymal vein.
h | Periventricular lesion with branching veins. i | Confluent lesions with multiple veins.
61. PARAMAGNETIC RIM LESIONS
• An imaging measure reflective of chronic, active lesions.
• This measure may be useful in diagnosing progressive forms of MS as studies have demonstrated that
patients with progressive MS and greater disability have a higher proportion of lesions demonstrating
paramagnetic rim lesions.
• However, because paramagnetic rim lesions are visualized even in RIS and early RRMS (much like the
central vein sign), future studies are needed before this measure can be used as an imaging biomarker in
clinical settings.
61
62. BODY FLUIDS BIOMARKERS
• Blood biomarkers such as serum neurofilament light chain and glial fibrillary acidic protein (GFAP)
have demonstrated utility in prognostication and in disease monitoring, however, these markers are not
specific for MS-related tissue injury in isolation and it is unclear if they are useful as diagnostic biomarkers.
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Marker of
axonal
damage.
NfL
Marker of
astrocytes
damage.
GFAP
63. 63
• Neurofilaments are major components of the
axonal cytoskeleton, consisting of light (NfL),
intermediate and heavy chains that are released
from damaged neurons and axons in neurological
disorders.
• These neurofilament chains can be quantified in
the blood and CSF as a marker for neuroaxonal
damage in MS.
• Several studies have demonstrated that levels of
NfL in cerebrospinal fluid are higher in patients
with CIS who convert to MS and patients with
RIS who develop a first clinical attack.
NfL
• In addition, higher levels of NfL are associated with
greater disability, more frequent relapses, higher
numbers of T2-hyperintense and gadolinium enhancing
lesions on MRI and more severe brain atrophy.
• In patients with RRMS, higher levels of NfL predicted
more severe disability and evolution to SPMS after 14
years of follow-up, whereas in patients with PPMS or
SPMS, levels of NfL predicted the annual EDSS
increase.
64. OPTICAL COHERENCE TOMOGRAPHY.
• OCT can generate high-resolution images of the retina in a non-invasive, rapid and reproducible
manner and in a multicenter setting.
• In MS, OCT might show asymptomatic optic nerve involvement in patients with CIS and might predict
conversion to MS.
• The combined ganglion cell-inner plexiform layer and the retinal nerve fibre layer (RNFL) have been
the two most frequently studied layers of the retina in patients with MS.
• In patients with acute optic neuritis, dynamic modifications of RNFL thickness, characterized by an
initial increase owing to acute inflammatory oedema followed by atrophy within the subsequent 3–6
months, have been detected, therefore, the occurrence of substantial and irreversible damage is
detectable only after 6 months.
64
65. OPTICAL COHERENCE TOMOGRAPHY.
• Meta-analyses of OCT studies have demonstrated RNFL thinning to be most marked in the temporal
quadrant, which is the receiving region for the macular fibres.
• In addition to the RNFL, technological advances in OCT have allowed the segmentation of other retinal
layers, such as the ganglion cell layer (GCL), which has been shown to have a different response to
optic neuritis attacks, as this layer has a faster onset of thinning without any acute phase oedema.
For this reason, macular GCL thickness has been proposed as a superior early indicator of neural
changes following optic neuritis.
• RNFL thinning has been shown in all MS phenotypes and can start in patients with CIS. RNFL is more
severe in patients with SPMS than in those with RRMS independent of a history of previous optic neuritis.
• Progression of RNFL and GCL thinning correlates with visual deficits and worsening disability. In
addition, correlations between OCT parameters and atrophy of the whole brain and grey matter as
detected using MRI have been observed.
65
66. GREY MATTER DAMAGE
• Improvements in MRI techniques have enabled the measurement of grey matter pathology in vivo,
including focal lesions, tissue loss and neuronal abnormalities.
• Focal lesions in the cortex are a distinctive feature in patients with MS, and the presence of at least
one cortical lesion identifies patients with CIS at higher risk of developing MS.
• Cortical lesions are highly specific for MS, as they have not been detected in other neurological
disorders that can mimic MS so far, such as NMOSD or migraine.
• The presence of both cortical lesions and grey matter atrophy are more pronounced in patients with
progressive MS and correlates with more severe disability.
• In addition, the quantification of cortical lesions and grey matter atrophy enables the long-term
prognostication of worsening of disability and cognitive dysfunction.
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