Neuroinflamm and WM diseases

  1. Who gets SPMS?
    • Older
    • Male
    • Motor onset
  2. Side-effect of Fingolimod?
    Macular oedema – Need OCT at baseline and after 3-4 months of treatment
  3. Side-effect of Dimethyl fumarate?
    Flushing – Give the DMF with food or with a daily aspirin to avoid
  4. Pontine perivascular enhancement extending into the cerebellum?
  5. Radial perivascular enhancement perpendicular to the ventricles and leptomeningeal enhancement?
    GFAP astrocytopathy – often paraneoplastic – USS ovaries for teratoma
  6. 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
  7. 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.
  8. Susac’s Syndrome
    • Microangiopathy
    • Brain, retina and cochlear causing triad of encephalopathy, sensorineural hearing loss and vision loss
    • Snowballs at corpus callosum on imaging.
  9. 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
  10. 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
  11. 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
  12. Dimethyl Fumarate - Tecfadera
    • Fumarole acid ester,
    • Unclear MOA
    • Flushing, GI upset, loose stools
    • Not to be used in pregnancy
  13. Teriflunomide
    • Inhibits pyramidine synthesis via a mitochondrial enzyme
    • Dihydro-orotate dehydrogenase
    • Diarrhoea, nausea, LFT derangement, alopecia
    • NEVER use in pregnancy
  14. Interferon
    • Can be associated with neutralising autoantibodies
    • Causes myalgia and depression
  15. Glateramer Acetate
    • Made of 4 random proteins that make up myelin basic protein 
    • MOA unclear
    • Can cause lipoatrophy at injection site
  16. Abnormal sleep movements and behaviours, OSA, gait instability, ataxia, dysarthria, dysphagia and central hypoventilation
    • Iglon-5
    • Tauopathy
  17. Metachromatic leukodystrophy?
    • Arylsulfatase deficiency
    • Tigroid stripes
    • Spares the U-fibres
  18. Krabbe disease
    • Globoid cell leukodystrophy
    • Galactosylcerebrosidase deficiency 
    • GALC gene mutation
  19. Tay-sachs
    • Hexosaminodase A deficiency
    • Leads to the accumulation of Fats in the brain
    • GM2 Gangliosidosis
  20. What are the three GM2 gangliosidoses?
    • Tay-sachs (HEXA)
    • Sandhoff's (HEXB)
    • Hexosaminodase activator deficiency
  21. 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
  22. Pelizaeus-Merzbacher disease
    • X-linked recessive Leukodystrophy
    • Mutation in the PLP-1 gene
    • Whistling sound when breathing
    • Ataxia, spasticity, seizures.
  23. 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
  24. 4 phenotypes of adrenoleukodystrohpy?
    • 1. Adrenoleukodystrohpy
    • 2. Adrenomyeloneuropathy
    • 3. Adrenal insufficiency only
    • 4. Asymptomatic
  25. Side effect of Fampridine?
    • Seizures
    • Contraindicated in renal failure
  26. Musty or musky odour from a fair child?
  27. X-linked dominant disease?
    • Aicardi syndrome
    • Lethal to males
    • Females have infantile spasms and developmental abnormalities
    • Assoc with chorioretinal lacunae
  28. What causes Zellweger syndrome?
    • Mutations in the PEX genes
    • Lead to absent peroxisomes and significant developmental abnormalities.
  29. Canavan disease?
    • ASPA gene mutation - aminoacyclase 2 deficiency
    • NAA (NAcetyl aspartate) accumulation in nerve fibres and myelin
    • Big head
  30. Conus and Cauda lesions lead to what kind of urinary problems?
    • Detrusor underactivity.
    • Large postvoid residuals, poor flow and hesitancy.
  31. How many urea cycle disorders are there?
  32. Whats the most common urea cycle disorder?
    • Ornithine Transcarbylmase deficiency
    • its the only X linked one, all the others are autosomal recessive.
  33. How do urea cycle disorders present?
    • Hyperammonemia
    • Encephalopathy
    • Resp Alkalosis
  34. What are the x-linked white matter diseases?
    • ALD
    • Pelizaeus-Merzbacher
    • Fabry's
  35. Which WM diseases have a frontal or occipital predominance?
    • Alexander - Frontal
    • ALD - Posterior
  36. 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
  37. IgG4 disease likes to attack which structures?
    Pretty much everything behind the eye but if the nerves are enlarged, its definitely IgG4
  38. 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
  39. 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
  40. What do you do for Cytokine response syndrome?
    • Supportive and symptomatic control
    • O2, Fluids, NSAIDS, Antihistamines, Steroids.
  41. Classic history for GABA-A encephalitis?
    • Treatment refractory seizures,
    • cognitive and behavioural symptoms and
    • multifocal T2 hyperintensities without gadolinium enhancement
  42. What is found histologically in an acute MS plaque?
    • T-cells
    • Reactive astrocytes and macrophages with myelin debris inside them
  43. What is found histologically in a chronic MS plaque?
    • Absence of oligodendrocytes
    • Astrocytic gliosis
  44. What should you check before giving IVIG?
    • IgA levels
    • If the patient has an IgA deficiency - they're more at risk of anaphylactic shock.
  45. 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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Neuroinflamm and WM diseases