Neuro disorders and MS Flashcards
Define Multiple sclerosis
an immune mediated inflammatory disease of the CNS characterised by demyelination (destruction of normal myelin)
Where are myelinated axons most commonly located?
White matter - thus diseases of myelin are indicative of white matter disorders
How is myelin formed and what is its function?
In CNS - formed by oligodendrocytes
In peripheral nerves- formed by Schwann cells
Function: insulates axons and increases conductance(transmission of action potential) along axon
Cause of MS?
Caused by a combo of environmental and genetic factors that result in a loss of tolerance of self proteins aka myelin antigens
Risk factors include EBV smoking low serum Vit D Genetics- HLA DR2
Pathogenesis of MS
characterised by an imbalance between immunoregulatory and proinflammatory immune cells.
The abnormalities in multiple sclerosis are confined to the
CNS; the peripheral nervous system is not involved. Patients with multiple sclerosis have numerous demyelinated plaques in the brain and spinal cord , often closely related to veins.
Acute plaques are soft and pink with ill-defined boundaries. Histologically, there is myelin breakdown and
phagocytosis by macrophages. Perivascular cuffing with
inflammatory cells (plasma cells and T lymphocytes) is
widespread in the acute plaque. * Essentially perivascular and parenchymal inflam involve macrophages and lymphocytes *
The plasma cells synthesise immunoglobulins, which can be detected in the CSF. B lymphocytes have also been identified at the edges
of acute plaques.
As myelin breakdown eventually subsides, reactive gliosis is established, giving rise to a chronic plaque. These appear as sharply defined, grey, lucent areas of demyelination in
which oligodendrocytes are scarce or absent. The inflammatory infiltrate subsides, leaving small numbers of perivascular lymphocytes at the edge of chronic plaques aka hypocellular.
Although oligodendrocytes can proliferate in an attempt
to repair myelin, successful remyelination of established
plaques probably never occurs. Axonal damage also occurs
in multiple sclerosis and correlates with the inflammatory activity in the white matter, contributing to progressive neurological
debility. Remaining axons have reduced caliber
Describe the macroscopic vs microscopic findings in MS
Macroscopic
essentially well demarcated white matter plaques
-cavitating when old plaque
-yellow when more acute
Can affect brainstem(midbrain,pons and medulla), cerebellum, spinal cord and cerebral hemispheres
Microscopic
Preservation of axons
Macrophages and lymphocytes
Diagnosis of MS?
Primarily is a clinical diagnosis McDonald Criteria:
-Objective demonstration of dissemination of CNS lesions in both space and time based on either clinical findings alone or a combination of clinical and MRI findings
CSF analysis(via lumbar puncture) and SPEP(serum protein electrophoresis)
-Oligoclonal bands (OCBs) support a diagnosis of MS via SPEP
-increased lymphocytes and Igs
-myelin basic protein
Bloods : ENA, ANCA, ANA, Lyme, HIV, VDRL, anti aquaporin-4 antibodies, anti MOG antibodies
Optical coherence tomography/ Visual evoked potentials
-Delayed P100 potentials supportive of MS diagnosis using electroencephalography (P100 assesses conduction along optic nerve- usually slowed in pts with MS)
What are the presenting symptoms of MS?
Fatigue++ Visual loss, optic neuritis Acute transverse myelitis Trigeminal neuralgia Diplopia Gait/balance disturbance Vertigo Bladder dysfunction Lhermitte’s sign -Neck flexion results in rapid tingling or electric shock-like feeling that passes down the spine and into the limbs Uhtoff’s phenomenon -Raised body temperature can result in an exacerbation of symptoms
Typical Clinical course of MS
The course of MS is variable, but commonly there are multiple relapses followed by episodes of remission; typically,
recovery during remissions is not complete. As a consequence, over time there is usually a gradual, often stepwise, accumulation of neurologic deficits
What are the subtypes of MS?
Clinically isolated syndrome-
-used to describe a first episode of neurologic symptoms that lasts at least 24 hours and is caused by inflammation and demyelination in one or more sites in the central nervous system (CNS)
-A single clinical syndrome suggestive of demyelination with accompanying physical signs on examination
-May include: optic neuritis, brain stem syndrome or partial myelitis; can be multifocal (more than one sign/symptom) or monofocal (one sign/symptom)
-A risk for developing MS but not all cases of CIS develop MS
-increased risk of conversion to MS; Abnormal baseline brain MRI
Asymptomatic spinal cord lesions
Presence of unmatched oligoclonal bands in the CSF i.e. present in CSF but not in serum
Relapsing-remitting MS
-Majority of cases are relapsing-remitting at onset
-this is a clinical diagnosis
-Diagnosis based on the concepts of dissemination in time and dissemination in space
-History of relapses suggestive of demyelination with periods of remission and must have accompanying physical signs on exam
-‘Active’ or ‘inactive’
Based on relapses (diagnosed by history and exam) and MRI activity
Secondary progressive MS
-A progressive myelopathy
Onset begins when walking distance is restricted to approximately 500m
-Symptoms include: ambulatory dysfunction (stick/wheelchair), urinary dysfunction (catheter), pain, depression, fatigue
-May experience relapses
-A clinical diagnosis – no confirmatory tests for diagnosis of SPMS
-‘Active’ with or without progression
-‘Inactive’ with or without progression
-Based on relapses and MRI activity
Primary progressive MS (10-20%pts) Accounts for 15% of cases of MS
-Progressive myelopathy
-Begins later in life – mean age onset in 50s
-Disability accumulates quicker
-Approximately 10% of cases may have superimposed relapses
-Male: female ratio closer to 1:1
-‘Active’ with or without progression
-‘Inactive’ with or without progression
-Based on relapses and MRI activity
Diagnosis of PPMS
One year of disease progression (retrospectively or prospectively confirmed)
Plus 2 of 3 of the following:
-Evidence of DIS on brain MRI
-Evidence of DIS in the cord based on ≥2 T2 lesions in the cord
-Positive unmatched OCBs in the CSF
What is the MRI contrast media used for diagnosis of MS?
GADOLINIUM
MRI+contrast (Gadolinium) -MS
If gadolinium enhanced- active plaque
Describe the Mc Donald Criteria
- MRI criteria
- Essentially when MS has been diagnosed clinically based on dissemination in time and space: the diagnosis may be confirmed using MRI
- If person has two or more attacks and there is objective clinical evidence for two or more lesions w a historical evidence of a prior attack- no additional data needed as clinical evidence is sufficient(however MRI can be done if so desired but must be consistent w MS)
- Two or more attacks w/ object clinical evidence of 1 lesion; additional data via MRI to show dissemination in space OR by further awaiting clinical attack compromising a different site
- One attack with 2 or more lesions; additional data via MRI showing dissemination in TIME OR await second clinical attack
Define dissemination in time
onset of two CNS disorders separated by at least one month in time
Demonstrated by either:
- A new T2 and/or Gd enhancing lesion(s) on follow up MRI, with reference to baseline MRI
- Simultaneous presence of asymptomatic Gd-enhancing and non-enhancing lesions at any time
- Dissemination in space and unmatched oligoclonal bands in the CSF
Define dissemination in space
Lesions in two separate places in the central nervous system e.g. Optic nerve and brain stem or spinal cord and cortex
more than/equal to 1 T2 lesion in 2 of 4 areas in CNS: Periventricular Juxtacortical Infratentorial Spinal cord Cortical/juxtacortical
The MS lesions on a T2-weight MRI show up as hyperintense lesions, or “bright spots” and are often referred to as plaques
Describe how MS related demyelination might clinically manifest according to neuroanatomical location
Optic neuritis
- Unilateral visual loss
- Red vision affected first
- Pain on eye movement
- Pain typically does not last more than two weeks
- Signs of optic neuritis
- Rapid Afferent Pupillary Defect ; pts pupils constrict less when a bright light is swung from the unaffected eye to the affected eye
- optic disc swelling (Acute)
- optic disc pallor (chronic)
Brain stem/cerebellar symptoms -Facial palsy -Ataxia -Diploplia -Trigeminal neuralgia: trigeminal neuralgia, even mild stimulation of your face — such as from brushing your teeth or putting on makeup — may trigger a jolt of excruciating pain Signs in brain stem syndrome *Nyastagmus *one and a half syndrome-affecting both eyes, in which one cannot move laterally at all, and the other can move in only one lateral direction (inward or outward)
Spinal cord symptoms: Lhermitte’s symptom Numbness Urinary urgency Faecal incontinence Sexual dysfunction Spastic paraplegia
Signs a/w spinal cord damage : Weakness Increased tone +/- clonus Brisk reflexes Upgoing plantar response Brown Sequard syndrome -loss of pain, temp, light touch on opp side -loss of motor function, vibration, position, deep touch sensation on same side as cord damage
Cerebral hemisphere symptoms Cognitive impairement Hemiparesis Seizures Encephalopathy Signs: -brain damage -paralysis -spatial/perceptual deficits or speech/language defcits -behavioral style: quick, impulsive/ slow, cautious -memory deficits (performance/language)
What are the differential diagnoses for MS?
Ischaemia – small vessel ischaemic abnormalities on brain scan or migraine
Functional disorder (psychogenic)
Inflammatory – sarcoid, lupus
Infection – syphilis, listeria, lyme
Nutritional – B12, zinc/copper
Metabolic – central pontine myelinolysis, mitochondrial
Genetic – eg Fabry’s disease ( lysosomal storage)
How do you take an adequate history for MS
Determine disease activity i.e. History of new/recent relapses
Determine symptoms related to prior relapses:
Fatigue
Bladder dysfunction
Pain
Spasticity
Social History is extremely important*: adaptations to bathroom, transfers from chair, home help etc.
