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Side-effect of Fingolimod?
Macular oedema – Need OCT at baseline and after 3-4 months of treatment
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Side-effect of Dimethyl fumarate?
Flushing – Give the DMF with food or with a daily aspirin to avoid
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Pontine perivascular enhancement extending into the cerebellum?
CLIPPERS
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Radial perivascular enhancement perpendicular to the ventricles and leptomeningeal enhancement?
GFAP astrocytopathy – often paraneoplastic – USS ovaries for teratoma
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If it looks like TTP (Thrombotic) and smells like TTP (thrombocytopaenic) but they don’t have purpura and instead have Leukopenia – what is it?
Probably Paroxysmal Nocturnal Haemaglobinuria
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Bechet’s
- Vasculitis causing ulcers, uveitis and skin lesion
- CNS Bechet’s causes VST or parenchymal lesions
- It can cause recurrent meningoencephalitis, CN palsies, ataxia and pyramidal signs.
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Susac’s Syndrome
- Microangiopathy
- Brain, retina and cochlear causing triad of encephalopathy, sensorineural hearing loss and vision loss
- Snowballs at corpus callosum on imaging.
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Natalizumab
- Antibody against the cellular adhesion molecule alpha4-integrin
- Binds to lymphocytes and prevents adherence at the endothelium of the BBB
- Reduces entry of immunologically active cells to the CNS compartment
- 60-70% reduction in exacerbation rate
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Alemtuzumab
- CD52 mab
- Proposed mechanism is antibody dependent lysis of B and T cells, causing reduced immune injury in MS patients
- Hyperthyroidism and ITP can occur
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Fingolimod
- All active modulator of sphingosine-1 phosphate (S1P) receptors
- Superagonist at the S1P receptor
- Induces uncoupling and internalisation of that receptor
- Macular oedema, bradycardia, bronchitis and deranged LFTs
- Associated with severe VZV infections
- Not to be used in pregnancy
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Dimethyl Fumarate - Tecfadera
- Fumarole acid ester,
- Unclear MOA
- Flushing, GI upset, loose stools
- Not to be used in pregnancy
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Teriflunomide
- Inhibits pyramidine synthesis via a mitochondrial enzyme
- Dihydro-orotate dehydrogenase
- Diarrhoea, nausea, LFT derangement, alopecia
- NEVER use in pregnancy
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Interferon
- Can be associated with neutralising autoantibodies
- Causes myalgia and depression
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Glateramer Acetate
- Made of 4 random proteins that make up myelin basic protein
- MOA unclear
- Can cause lipoatrophy at injection site
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Abnormal sleep movements and behaviours, OSA, gait instability, ataxia, dysarthria, dysphagia and central hypoventilation
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Metachromatic leukodystrophy?
- Arylsulfatase deficiency
- Tigroid stripes
- Spares the U-fibres
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Krabbe disease
- Globoid cell leukodystrophy
- Galactosylcerebrosidase deficiency
- GALC gene mutation
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Tay-sachs
- Hexosaminodase A deficiency
- Leads to the accumulation of Fats in the brain
- GM2 Gangliosidosis
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What are the three GM2 gangliosidoses?
- Tay-sachs (HEXA)
- Sandhoff's (HEXB)
- Hexosaminodase activator deficiency
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Adrenoleukodystrophy
- Think lorenzo's oil
- X-linked disorder
- Mutation in the ABCD1 gene (ATP-binding cassette type D1)
- Will present with adrenal deficiency and elevated VLCFA
- Occipital predominant demyelination that spares the U-fibres
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Pelizaeus-Merzbacher disease
- X-linked recessive Leukodystrophy
- Mutation in the PLP-1 gene
- Whistling sound when breathing
- Ataxia, spasticity, seizures.
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Rough rule of thumb for EDSS?
- 5.5 - No walking aids
- 6.0 - 1 walking aid
- 6.5 - 2 walking aids
- 7.0 - Wheelchair bound
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4 phenotypes of adrenoleukodystrohpy?
- 1. Adrenoleukodystrohpy
- 2. Adrenomyeloneuropathy
- 3. Adrenal insufficiency only
- 4. Asymptomatic
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Side effect of Fampridine?
- Seizures
- Contraindicated in renal failure
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Musty or musky odour from a fair child?
PKU
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X-linked dominant disease?
- Aicardi syndrome
- Lethal to males
- Females have infantile spasms and developmental abnormalities
- Assoc with chorioretinal lacunae
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What causes Zellweger syndrome?
- Mutations in the PEX genes
- Lead to absent peroxisomes and significant developmental abnormalities.
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Canavan disease?
- ASPA gene mutation - aminoacyclase 2 deficiency
- NAA (NAcetyl aspartate) accumulation in nerve fibres and myelin
- Big head
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Conus and Cauda lesions lead to what kind of urinary problems?
- Detrusor underactivity.
- Large postvoid residuals, poor flow and hesitancy.
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How many urea cycle disorders are there?
5
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Whats the most common urea cycle disorder?
- Ornithine Transcarbylmase deficiency
- its the only X linked one, all the others are autosomal recessive.
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How do urea cycle disorders present?
- Hyperammonemia
- Encephalopathy
- Resp Alkalosis
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What are the x-linked white matter diseases?
- ALD
- Pelizaeus-Merzbacher
- Fabry's
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Which WM diseases have a frontal or occipital predominance?
- Alexander - Frontal
- ALD - Posterior
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Young man with Amnesia, weight gain, decreased libido, somnolence. Reduced vertical gaze, inflammatory CSF and T2 hyperintensity in the limbic and diencephalic structures?
- Anti-ma2
- Probably has a testicular tumor
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IgG4 disease likes to attack which structures?
Pretty much everything behind the eye but if the nerves are enlarged, its definitely IgG4
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How long should pregnancy be avoided for after MS DMTs?
- 2 months for fingolimod,
- 4 months for alemtuzumab,
- 6 months for cladribine,
- 12 months for ocrelizumab,
- 2 years for teriflunomide
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How do you classify and manage the immune-effector cell associated neurotoxicity (ICANS)?
- Icans 1: Alert without seizure - no Rx
- Icans 2: mild encephalopathy with brief seizure - Dex
- Icans 3: Encephalopathic with seizure >5mins - Methylpred
- Icans 4: As 3 with hemiparesis/paraparesis and diffuse cerebral oedema.
- They can also get a cytokine storm syndrome
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What do you do for Cytokine response syndrome?
- Supportive and symptomatic control
- O2, Fluids, NSAIDS, Antihistamines, Steroids.
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Classic history for GABA-A encephalitis?
- Treatment refractory seizures,
- cognitive and behavioural symptoms and
- multifocal T2 hyperintensities without gadolinium enhancement
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What is found histologically in an acute MS plaque?
- T-cells
- Reactive astrocytes and macrophages with myelin debris inside them
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What is found histologically in a chronic MS plaque?
- Absence of oligodendrocytes
- Astrocytic gliosis
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What should you check before giving IVIG?
- IgA levels
- If the patient has an IgA deficiency - they're more at risk of anaphylactic shock.
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18-year old male with progressive painless bilateral visual failure with normal fundoscopy - what differentials should you consider?
- Intracranial germinoma
- LHON
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