High Yield (NZ) Flashcards

Question

What are key syndromes for neonatal period?

Answer 1

Benign familial neonatal epilepsy * AD * Within 7 days * Tonic clonic seizures Ohtahara syndrome * Tonic * Can develop into infantile spasms Early myoclonic encephalopathy * Myoclonic seizures Can develop into infantile spasms

Answer 2

* EEG does not rule out a diagnosis of epilepsy * Should not be ordered in unsure whether events are epileptic seizures or not * Should be performed for all children who have epileptic seizure as essential for diagnosing epilepy stpe and making epilepsy syndrome diagnosis * Making this diagnosis helps to direct therapy, direct further Ix, prognostic info Timing - single epileptic seizure - within 8 weeks, 2 or more epileptic seizures - within 2 weeks, suspected developmental or epileptic encephalopathy - as soon as possible - eg within 48 hours for infantile spasms

Answer 3

* Half of children with epilepsy will have normal EEG - normal EEG does not exclude * Only capturing 20 mins in time * Gold standard is video capturing EEG of ictal event- difficult in practice * Rolandic - no sleep obtained * Absence - no hyperventilation, Temporal lobe events - No HV, no sleep deprivation, sampling errors

Answer 4

* 1-2 Hz spike wave - 98% * 3 Hz spike wave - 97% * Fast rhythmic activity - 97% * Temporal spikes - 90% * Occipital spikes - 90% * Centro-temporal spikes - 55-85% Spikes - 2-3% people without epilepsy will have

Answer 5

* Develop epilepsy before aged 3 * Any suggestion of focal epileptic seizure onset on Hx, Ex or EEG * Epileptic seizures continue in spit of first line medications * Not required in genetic generalised epilepsies (or clear genetic focal epilepsy) Subtle lesions may be hard to find - repeat imaging

Answer 6

* 5 minutes or more of continous clinical and/or electrographic seizure activity or recurrent seizure activity without recovery * Most Sz last less than 5 mins, if seizures until then unlikely to stop spontaneously * T1 - 5 mins - time when seizures unlikely to cease spontaneously, abortive Tx introduced T2 - 30 mins - time to neuronal injury with generalised convulsive seizures - due to hypoxia, need to escalate to more aggressive Mx

Answer 7

* ABCS * IV access * 2 x midazalom or benzo -not ongoing doses and benzos downregulate GABA receptors and make refractory to further AEDs * AED - keppra or phenytoin * Earliest possible termination of seizure to prevent neuronal damage * EEG monitoring Search for cause - glucose, Ca

Answer 8

* Buccal midazolam 2.5 - 10mg Rescue medication - over 3 months, prolonged febrile or afebrile tonic and/or clonic seizures (> 5 minutes)

Answer 9

Generalised: * GTC: * Over 3 - sodium valproate * Under 3 - clobazam, levetiracetam, lamotrogine * Myoclonic - Valporate, clobazam * Tonic/atonic - Valproate, clobazam Focal * Carbamazepine Lamotrogine - Han Chinese HLA-B 1502

Answer 10

Absence epilepsy * 1st - Ethosuximide (same efficacy as valproate but less side effects) * 2nd - Valproate, lamotrogine * 3rd - Levetiracetam, clobazam, acetazolamide Juvenile myoclonic epilepsy * 1st - Valproate * 2nd - lamotrogine, levetiracetam, topiramate Childhood epilepsy with CT spikes * 1st - carbamazepine, lamotrogine 2nd - levetiracetam, valproate

Answer 11

Infantile spasms * 1st - Prednisolone/ACTH - 2 weeks then taper * 1st (with tuberous sclerosis) - Vigabatrin * 2nd - Vigabatrin, ketogenic diet Dravet syndrome * 1st - Valproic acid, clobazam * 2nd - levetiracetam, ketogenic diet, stiripentol Lennox Gastaut syndrome * 1st - Valproate, clobazam 2nd - ketogenic diet, rufinamide, felbamate

Answer 12

* TS - vigabatrin, mTOR inhibitors * SCN1a (Dravet) - valproate, clobazam, lev, CBD, fenfluramine * KCNQ2 (Developmental and epileptic encephalopathy - carbamazepine, phenytoin * PRRT2 (benign familial infantile seizures- carbamazepine * SLC2A1 (absence or myoclonus) associated GLUT1 - ketogenic diet HLA-B*1502 antigen - identify individuals at high risk of carbamazepine induced SJS

Answer 13

* GABA - valproate, vigabatrin, benzos, barbiturates, gabapentin * Na + channels - carb, lamotrogine, phenytoin * SV2A - levetiracetam * NMDA - valproate Ca - Ethosux

Answer 14

* Vagal nerve stimulation * Ketogenic diet * Epilepsy surgery Immunomodulation - steroid, IVIG

Answer 15

* 1/3,000 * Higher risk with neurodisability, CP, can't clear secretions - 25% over 20 years * High seizure frequency, convulsive During or shortly after seizure - resp failure, seizure induced bradyarrythmias

Answer 16

* Weakness and sensory * Distribution - single limb, patchy, proximal, distal * Acuity - acute vs chronic * PHx - was child previously normal? * Trauma, illness, meds, immunisations, toxin exposure Rate of deterioration

Answer 17

* Expressionless, sunken cheeks, bilateral ptosis, unable to elevate corners of mouth * Open mouth High arched palate- way it descends is how strong muscles are

Answer 18

* Nerve disease - mainly peripheral * SMA - generalised * SMA III and limb girdle muscle dystrophy - Duchenne - proximal Facio - scapular humeral dystophy - scapula, facial weakness

Answer 19

Gower sign * Sit up from chair, have to assist self standing up * Proximal weakness Myotonia * Difficult opening fist from clenched fist * Induce mytonia by tapping on thenar eminenence- coming in Fasciculations * Denervation Scapular winging * Limb girdle dystrophies Facio-scapular humeral dystrophy

Answer 20

* Numbness * Pain * Sensitivity to touch * Coordination difficulty - proprioception * Weakness Bladder/bowel dysfunction

Answer 21

Acquired -Is and Ts * Inflammation * Iatrogenic - chemo agents * Infection * Trauma * Toxic - organophosphates * Tumour Congenital * Genetic/metaboilc Maternal - check mother

Answer 22

* Gene testing CMT1a - 17p11PMP-22 (chromosome 17 duplication)

Answer 23

* Muscle wasting, difficulties with proprioception, co-ordination, balance Family history often positive - dominant inheritance

Answer 24

* Latency - Speed of conduction - time relationship between stimulus and the response (speed of conduction) Amplitude - How well preserved the signal is- voltage relationship between stimulus and response (preservation of voltage)

Answer 25

* Examines intergrity of myelin sheath * Wire intact - conducts faster * Eg - CMT Type 1 - demyelinating neuropathies * Conduction velocity decreases below 50% in CMT Type 1 * Sensory fibres are most vulnerable and affected first In severe demyelination, sensory responses may be altogether absent

Answer 26

* Any pathology which reduces number of nerve fibres or muscle fibres will reduce amplitude * Lose nerve fibres * Eg - CMT Type 2 - axonal neuropathies * Sensory fibres affected first, decreased amplitude * Progresses, motor amplitudes decreases Velocity also slowed down due to decrease of fast conducting fibres

Answer 27

Type 1 - demyelinating -loss myelin and slower conduction, decreased conduction velocity Type 2 - axonal loss - less muscle fibres, decreased amplitude

Answer 28

Demyelinating - decreased conduction velocity * CMT 1 and 4 * HMSN 3 * Krabbe * MLD Axonal - decreased amplitude or block * CMT 2 Inflammatory CIDP

Answer 29

* Opthalmoplegia - paralysis of extraocular eye movements * Ptosis CXR * Thymus hyperplasia Enlarged thymus - benign * Problem at neuromuscular junction ACh receptor blocked by antibody

Answer 30

* Accumulation of ACh, block NMJ * Amplitudes and conduction velocities normal * Slow repetitive stimulation of muscle - decremental response * Each subsequent response lower and lower Could also be other things that block NMJ - eg organophosphate phosphates

Answer 31

* Dystrophy - degenerative loss and destruction of previously normal architecture, relatively high CK Myopathy - abnormal architecture, minimal increase in CK

Answer 32

* Recessive * 2nd most common after CF * 1 in 40-60 carrier * 1/10,000 * SMA0 - all 4 copies deleted, lethal in utero * Type 1 SMA - lost SMN1, have SMN2 * Type 2 SMA - 3 x SMN2, lost 1 SMN1 * Type 3 SMA - 4 x SMN * Loss of SMN1 protein Multiorgan

Answer 33

* Muscle function and individual motor units * Needle placed into muscle or motor unit What is pathology seen on EMG? * SMA - active denervations, random potentials, fibrilliations - seen clinically as fasciculations Myotonia - high frequency discharges vary in amplitude and frequency

Answer 34

* 1:3,000 * Autosomal dominant * 30-50% new mutations * Due to mutations in NF1 gene * Tumour suppressor gene - codes for neurofibromin - regulates cell signal transduction pathways 100% penetrant by 5 years

Answer 35

Diagnostic Criteria - requires 2 or more 1. Equal or more than 6 café au lait patches - (not uncommon to see 1-2) ,> 5mm prepubertal, > 15mm postpubertal 2. 1st degree relative with NF - must examine parents/siblings 3. Axillary or inguinal freckling - develop by ~ 5 4. Optic nerve glioma - 15%, normal vision, symptomatic 2%, loss of vision/proptosis if expands. Treat with carboplatin - critical, can preserve vision 5. 2 neurofibromas or 1 plexiform neurofibroma - neurofibroma - peripheral nerve sheath tumour, benign, plexiform neurofibroma - more extensive tumour, can become malignant 6. Lisch nodule - tan coloured harmatomas of iris, do not affect vision, Opthal with slit lamp Distinctive osseous lesions - thinning of long bones, long bone/sphenoid wing dysplasia, pathological #

Answer 36

UBOs - unidentified bright objects * Hyperintense regions on T2 MRI * Cerebellum > brainstem > internal capsule * Benign * Present in 2/3 * Increase in size until 10 y.o then often disappear Seizures * 5% * ? Assoc with UBOs * If focal, consider intracranial malignancy Learning difficulties * 50%, ID 5% * Lower IQ but not everyone CNS Tumours * Optic nerve gliomas common * Other CNS tumours not as common (but x 5 risk than general population) Malignant Peripheral Nerve Sheath tumours * Neurofibrosarcoma * Pre-existing plexiform neurofibromas * Painful, rapid growth * Highly malignant - PET and surgery Spinal Neurofibromas * Infiltrate spinal * Extensive and painful Scoliosis * Most common in adolescence Short stature * 10-15% Macrocephaly * Common, related to stature, brain volume increased Hypertension * 6% - renal artery stenosis, phae Pubertal disturbance * Rare, consider CNS lesion Mortality Mean age death 54/59

Answer 37

Yearly: * Learning evaluation and formal psychometric evaluation * Neuro assessment * BP * Scoliosis * 6-12 monthly Opthal Routine neuroimaging not recommended (controversial)

Answer 38

Genetics * Autosomal dominant * Up to 50% new mutations * Due to mutations in NF2 gene * Tumour suppressor gene - codes for merlin - merlin links between membrane proteins/cell cytoskeleton * Fully penetrant * Non sense/frameshift - severe disease Missense - milder

Answer 39

Diagnostic Criteria - one of 1. Bilateral vestibular schwannoma 2. First degree relative with NF2 AND unilateral vestibular schwannoma or 2 of meningioma, schwannoma, glioma, neurofibroma, lenticular opacities (cataracts) 3. Multiple meningiomas AND unilateral vestibular schwannoma, 2 of schwannoma, glioma, neurofibroma, lenticular opacity

Answer 40

CNS Tumours * Almost all will have bilateral vestibular schwannoma by aged 30 Neurological lesions * Vestibular schwannoma 95% * Meningiomas * Spinal tumours Eye lesions * Cataracts 60-80% * Retinal harmatomas Other * Unilateral hearing loss 35% * Focal weakness * Tinnitus * Bilateral hearing loss * Balance dysfunction * Seizure * Focal sensory deficit * Visual loss * DON'T get > 6 CAL/Lisch nodules/axillary freckling Average age of death 36

Answer 41

* Average age death 36 * Spinal tumours in 2/3 * Annual MRI * Surgical Mx of vestibular schwannoma * Monitor and treat cataracts as needed * New Rx - Avastin (bevacizumab) - shrinks vestibular schwannomas

Answer 42

* Autosomal dominant (2/3 new, 1/3 FHx) * Abnormal TSC1 or TSC2 (tumour suppressor gene) --> encode tuberin and hamartin --> abnormal signalling/expression --> hamartomas * Multiple benign harmartomas (benign growth disorganised cells) of multiple organs * Tuber = potato

Answer 43

SKIN 3 Hypomelanotic depigmented lesions (Ash leaf) · May only be seen on Woods lamp · Present in nearly all Shagreen patch · Leathery · 60% Ungual/periungal fibroma · Nail Facial Angioma or Forehead plaque · Adenoma sebaceum "acne like" - 75% · Butterfly/malar region · Forehead plaque - distinctive brown fibrous plaque on forehead - 25%

Answer 44

``` BRAIN (>75%) · Cortical tubers "potatoes" · Subependymal nodules · Astrocytoma - subependymal giant cell astrocytoma · Can cause hydrocephalus · White matter radial migration · Seizures · ID Behavioural issues ```

Answer 45

``` RENAL (common 80%) · Renal angiomyolipomas · Can bleed · Multiple renal cysts - benign · Renal cell carcinoma 3% ``` CARDIAC · Cardiac angiomyolipomas · Rhabdomyomas OTHER Opthal · Retinal lesions (harmatomas), Mulberry lesions RESP · LAM - lymphangiomyomatosis Complications · 85% with TS have Cx · Seizures - infantile spasms - 20% will have TS, myoclonic, partial, GTCS, can be refractory to Tx · Intellectual Disability 50% - mild to severe Behaviour - ADHD, autisim, sleep

Answer 46

``` Surveillance • Brain - MRI, EEG • Renal - imaging • Cardiac - Echo, ECG • Resp ``` Mx • mTOR inhibitors - sirolimus, everolimus • Renal - embolisation • Seizures - vigabactrin Genetic counselling • Must assess parents - Woods lamp, MRI brain, renal, opthal If normal, recurrent risk 2% (not 0% gonadal mosaicism)

Answer 47

* Brain inflammation * Infectious 75% - enterovirus 10%, parechovirus 10%, bacterial 8%, influenza 6%, HSV 6%, mycoplasma pneumoniae 6% * Immune - 25% ADEM 18%, anti NMDA 6% * 5% mortality - most from infectious * 1/3 have mod-severe neurological sequale Study excluded neonates

Answer 48

* Altered mental state > 24 hours (with no alternative cause) * 2 for possible, 3 probable/confirmed: * Fever wtihin 72 hours * New seizures (not fully attributable to pre-existing disorder) * New onset focal neuro findings * CSF WCC > 5 * Neuroimaging abnormality consistent with encephalitis * EEG abnormality consistent with encephaliitis And EXCLUSION of encephalopathy caused by trauma, metabolic, tumour, alcohol, sepsis, other infectious causes

Answer 49

What is it and clinical presentation? * Monophasic inflammatory disease * Age 5-8 * Often a preceeding acute systemic infection or vaccination * Prodrome - fever, malaise, headache, myalgia, nausea and vomiting * Rapidly progressive encephalopathy not explained by fever * Behavioural change or altered consciousness - must be present * Other polyfocal neurological signs - CN palsies, hemiparesis, ataxia, myelopathy or optic neuritis Abnormal MRI

Answer 50

* Unilateral/bilateral pyramidal signs * Acute hemiplegia * Ataxia * CN palsies * Visual loss due to optic neuritis * Seizures * Spinal cord involvement - often silent, inflamm protocols always have MRI brain and spine Impairment of speech

Answer 51

* Mild pleocytosis (less than 50 WCC) * Oligoclonal bands uncommon ADEM What are common MRI findings? * T2 hyperintense lesions (T2 CSF white but FLAIR CSF signal suppressed) * Deep and subcortical white matter * Sparing of periventricular white matter and corpus callosum * Deep grey matter (thalamic and basal ganglia) less common * Cerebellum, brainstem and optic nerves Spinal cord involvement detected in absence clinical defect

Answer 52

* Infections bacterial, viral and fungal - should be covered with aciclovir, cannot tell clinically between ADEM and acute viral encephalitis * Metabolic - organic aciduria, mitochondial disease * Autoimmune disease - SLE, Behcet's, sarcoidosis, primary CNS vasculitis * Autoimmune encephalitis * Macrophage activation - eg HLH * Malignancy - lymphoma, glioma MS

Answer 53

* Antibiotics and aciclovir while excluding other diagnoses * 1st line - Steroids - methylprednisolone 3-5/7 -immunosuppressive * 2nd line - IVIG - 2-5/7, steroid unresponsive * Plasmapheresis - acute fulminant demyelinating disease Surgical decompression - raised ICP and continued clinical deterioration

Answer 54

* Rapid improvement usually over days * Full recovery 1-6 months * Full recovery 57-89% * Minor residual deficits 20-30% * Increased recognition of subtle neurocognitive deficits - subtle deficits in attention, executive function, behaviour when re-evaluated over 3 yers after ADEM Lower IQ, behavioural problems, lower educations achievement

Answer 55

* MOG positive * MOG - myelin oligodendrocyte glycoprotein * Protein expressed on surface of oligodendrocytes and myelin in CNS Plasma cells in blood produce antibodies, cross BBB, attack MOG protein on oligodendrocytes and myelin in CNS

Answer 56

* MOG associated demyelinating disease * Affect adult and children * Spectrum of conditions that can be MOG positive * Can be isolated ADEM ADEM + optic neuritis + longitudinally transverse myelitis

Answer 57

* 30% of all acquired demyelinating syndromes * 35% of relapsing disease Demyelinating syndrome and % MOG Ab positive * All acute demyelinating syndromes - 30% * ADEM 60% * Multiphasic ADEM (recurs after 3 months of initial) or ADEM-ON (optic neuritis) - 95% * Optic neuritis 37% Transverse myelitis 13%

Answer 58

· IV methylpred 3-5/7 (similar to ADEM of any cause) · 2nd line - IVIG · Longer steroid taper > 3 months - reduced risk of relapse Most relapses occur below 0.25-0.5mg/kg/day

Answer 59

· Multiphasic, recurrence · Commence maintanence therapy · Azathioprine, mycophenolate, rituximab - all decreases relapses but not all cases Monthly IVIG - least anount of relapses

Answer 60

· Rarer in children but earlier onset, higher disability score · Multiple episodes of CNS demyelination separated in time and space · Usually present with Clinically isolated syndrome, not ADEM Second event usually occurs in first 2 years

Answer 61

· Multiple episodes of CNS demyelination separated in time and space · 2 non encephalopathic clinical CNS events more than 30 days apart, more than 1 area of CNS · 1 non encephalopathic CNS event with MRI findings and a follow up MRI 1 new lesion · 1 episode ADEM (encephalopathy) and a non encephalopathic CNS event 3 months later, differnet area · Non ADEM event with associated MRI findings Aggressive - to start disease modifying treatment earlier

Answer 62

· ADEM: 5-8 yr, equal gender, viral prodrome common, encephalopathy required, seizures cmmon, MRI large lesions, CSF WCC variable, oligoclonal bands variable, MS: adolescent, F>M, viral prodrome uncommon, seizures rare, MRI over time new lesions, pleocytosis rare, oligoclonal bands common

Answer 63

· Methylprednisolone - immunosupressive, anti-inflammatory Disease modifying medications - Fingolimod (most used now), intergeron B 1a, copaxone, natalizumab

Answer 64

· Acquired inflammatory demyelinating disease · Mainly involved optic nerves, brainstem and spinal cord, severe attacks of optic neuritis and transverse myelitis · Childhood- late adulthood - ~39, female >male · Aggressive, 80% risk relapse · 50% chance of visual impairment or wheelchair dependent within 5 years Start maintenance therapy after 1st episode

Answer 65

Optic neuritis · Bilateral simultaneous or sequential ON rapid · Visual impairment > 60% Transverse myelitis · Complete - para or tetraparesis · Longitudinally extensive (>3 vertebral segments) · Mainly cervical or thoracic cord Can go to lower medulla - cause brainstem symptoms - vomiting, hiccups

Answer 66

· 1st line - steroid - high dose IV methylpred 3-5/7 · Long taper 3-6 months · 2nd line - IVIG · Plasma exchange Earlier escalation to PLEX had better outcomes

Answer 67

· 1/3 < 18 years · F>M · Anti-NMDA receptor antibodies - directed against GluN1 subunit of NMDA receptor · Best tested on CSF (15% missed on serum, MOG and AQ can be tested serum) High risk of underlying tumour, mainly ovarian teratoma - do US or MRI

Answer 68

· Behaviour change · Psychiatric - Psychosis, delusions, hallucinations, agitation, aggression, catatonia, 77% of adult patients first see psyhiatrist. Rarely only manifestation · Loss of speech, aphasia, perseveration, mutism · Dyskinesia - orofacial and oculogyric movements and perseverative (repetitive movements) · Seizures · Sleep disturbance/insomnia Dysautonomia

Answer 69

· Tumour removal · 1st line - methyprednisolone, oral pred or IV pulse 3-12 months · Severe patients - AND IVIG or PLEX · Rituximab - 2 weeks after first line, for 4 weeks · Prolonged admission/slow recovery - up to 18 months · Symptom control - anticonvulsants, benzos, clonidine, chloral, sodium valproate Caution with antipsychotic use - > 50% have dystonic reaction or NMS

Answer 70

· Neuronal surface or synaptic antigens - NMDA · Oligodendrocyte antibodies - MOG Astrocytes - AQP4

Answer 71

· Acute monophasic polyradiculoneuropathy · Acute inflamm demyelinating polyneuropathy (AIDP) in children, adults axonal · Criteria - progressive, ascending, bilateral legs then arms, reduced tendon reflexes · Elevated CSF protein - 1/3 have normal if early · Preceding infection 3-6 weeks earlier - Campylobacter 30%, CMV, EBV, mycoplasma

Answer 72

· Non specific pain - can be severe require gaba · Ascending weakness - 60% unable to walk, 10-15% require ventilation · Peak 7-10 days Autonomic dysfunction - bladder, constipation, hypertension, tachycardia

Answer 73

· Proximal nerve root affected, mainly demyelination · First week - prolonged/absent F waves · Prolonged distal latency - decrease conduction - myelin · Conduction block · Second week: · Reduced CMAP amplitude - lose motor fibres · Prolonged distal latency - less myelin · Reduced conduction velocity Sensory nerves affected 50%

Answer 74

· IVIG or PLEX · NOT steroid · Eculizumab ongoing trials · Tx related fluctuation - 10% · 5% have acute onset CIDP (chronic inflamm demyelinating polyneuropathy) · Other Sx - pain, bladder, bowel Rehab

Answer 75

· Opsoclonus - erratic eye movements · Myoclonic jerks · Ataxia - wide based gait, unsteady · Behavioural disturbance · Irritability · Cause - autoimmune inflammatory reaction targeting CNS tissue, triggered by either paraneoplastic or infectious event · 1-3 years 50% have neuroblastoma What are Ix? · CSF - normal or mild pleocytosis, oligoclonal bands 30%, B cell · Urine catecholamines - neuroblastoma · MRI · May need to repeat if normal OMA Syndrome What is Mx? · Tumour resection · Steroid - ACTH or pulse dex over oral pred · Aggressive Tx, aim for complete remission Improved developmental outcomes if aggressive with steroid + IVIG + ritux