Side-effect of Fingolimod?
Macular oedema – Need OCT at baseline and after 3-4 months of treatment
Side-effect of Dimethyl fumarate?
Flushing – Give the DMF with food or with a daily aspirin to avoid
Pontine perivascular enhancement extending into the cerebellum?
Radial perivascular enhancement perpendicular to the ventricles and leptomeningeal enhancement?
GFAP astrocytopathy – often paraneoplastic – USS ovaries for teratoma
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
- 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.
- Brain, retina and cochlear causing triad of encephalopathy, sensorineural hearing loss and vision loss
- Snowballs at corpus callosum on imaging.
- 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
- 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
- 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
Dimethyl Fumarate - Tecfadera
- Fumarole acid ester,
- Unclear MOA
- Flushing, GI upset, loose stools
- Not to be used in pregnancy
- Inhibits pyramidine synthesis via a mitochondrial enzyme
- Dihydro-orotate dehydrogenase
- Diarrhoea, nausea, LFT derangement, alopecia
- NEVER use in pregnancy
- Can be associated with neutralising autoantibodies
- Causes myalgia and depression
- Made of 4 random proteins that make up myelin basic protein
- MOA unclear
- Can cause lipoatrophy at injection site
Abnormal sleep movements and behaviours, OSA, gait instability, ataxia, dysarthria, dysphagia and central hypoventilation
- Arylsulfatase deficiency
- Tigroid stripes
- Spares the U-fibres
- Globoid cell leukodystrophy
- Galactosylcerebrosidase deficiency
- GALC gene mutation
- Hexosaminodase A deficiency
- Leads to the accumulation of Fats in the brain
- GM2 Gangliosidosis
What are the three GM2 gangliosidoses?
- Tay-sachs (HEXA)
- Sandhoff's (HEXB)
- Hexosaminodase activator deficiency
- 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
- X-linked recessive Leukodystrophy
- Mutation in the PLP-1 gene
- Whistling sound when breathing
- Ataxia, spasticity, seizures.
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
4 phenotypes of adrenoleukodystrohpy?
- 1. Adrenoleukodystrohpy
- 2. Adrenomyeloneuropathy
- 3. Adrenal insufficiency only
- 4. Asymptomatic
Side effect of Fampridine?
- Contraindicated in renal failure
Musty or musky odour from a fair child?
X-linked dominant disease?
- Aicardi syndrome
- Lethal to males
- Females have infantile spasms and developmental abnormalities
- Assoc with chorioretinal lacunae
What causes Zellweger syndrome?
- Mutations in the PEX genes
- Lead to absent peroxisomes and significant developmental abnormalities.
- ASPA gene mutation - aminoacyclase 2 deficiency
- NAA (NAcetyl aspartate) accumulation in nerve fibres and myelin
- Big head
Conus and Cauda lesions lead to what kind of urinary problems?
- Detrusor underactivity.
- Large postvoid residuals, poor flow and hesitancy.
How many urea cycle disorders are there?
Whats the most common urea cycle disorder?
- Ornithine Transcarbylmase deficiency
- its the only X linked one, all the others are autosomal recessive.
How do urea cycle disorders present?
- Resp Alkalosis
What are the x-linked white matter diseases?
Which WM diseases have a frontal or occipital predominance?
- Alexander - Frontal
- ALD - Posterior
Young man with Amnesia, weight gain, decreased libido, somnolence. Reduced vertical gaze, inflammatory CSF and T2 hyperintensity in the limbic and diencephalic structures?
- Probably has a testicular tumor
IgG4 disease likes to attack which structures?
Pretty much everything behind the eye but if the nerves are enlarged, its definitely IgG4
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
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
What do you do for Cytokine response syndrome?
- Supportive and symptomatic control
- O2, Fluids, NSAIDS, Antihistamines, Steroids.
Classic history for GABA-A encephalitis?
- Treatment refractory seizures,
- cognitive and behavioural symptoms and
- multifocal T2 hyperintensities without gadolinium enhancement
What is found histologically in an acute MS plaque?
- Reactive astrocytes and macrophages with myelin debris inside them
What is found histologically in a chronic MS plaque?
- Absence of oligodendrocytes
- Astrocytic gliosis
What should you check before giving IVIG?
- IgA levels
- If the patient has an IgA deficiency - they're more at risk of anaphylactic shock.
18-year old male with progressive painless bilateral visual failure with normal fundoscopy - what differentials should you consider?
- Intracranial germinoma