Neurology Flashcards
(136 cards)
1
Q
Focal seizure origin site if deja vu, epigastric rising, oral automatisms
A
Temporal lobe
2
Q
Focal seizure origin site if simple visual hallucinations
A
occipital lobe
3
Q
focal seizure origin site if presence of buzzing or ringing
A
primary auditory (temporal lobe)
4
Q
Focal seizure origin site if focal clonic activity
A
Dorsal frontal lobe
5
Q
Focal seizure origin if complex motor behaviour
A
Frontal lobe
6
Q
Treatment of focal seizures
A
Carbemazepine first line (PBS)
Lamotrigine better in clinical trials - non inferior efficacy and superior for adverse events
7
Q
Childhood absence epilepsy
A
Onset between age 4 and 10
Rarely have GTCs
8
Q
Juvenile absence epilepsy
A
Onset ove age 10
Absence common but also likely to have GTCs and may have myoclonus
Valproate effective
9
Q
Juvenile myeclonic epilepsy
A
Onset over age 10. ICK gene a risk actor
Early morning myoclonus or shortly after wakening
Worse with alcohol or sleep deprivation
GTCs common and absence can occur. Unlikely to achieve remission
Treat with valproate or lamotrigine if female of childbearing age
10
Q
Mesial temporal lobe epilepsy
A
Hippocampal sclerosis on MRI
Most common form of epilepsy
Risk factors: prolonged febrile convulsions + CNS infections
Presentation: auras, impaired awareness, dreamy states/deja vu, gustatory/olfactory hallucinations –> GTCs.
Unilateral hippocampal atrophy
Medically refractory in 60-90%
Surgery may be needed
Most common cause of drug refractory epilepsy
11
Q
Lennox Gastaut Syndrome
A
Onset early childhood
Multiple seizure types
Developmental disability
Characteristic EEG findings
12
Q
Generalised epilepsy management
A
Sodium valproate first line
Ethosuximide (absence only)
13
Q
Lamotrigine and pregnancy
A
2-3x fold metabolism during pregnancy due to oestrogen
Need close monitoring - low levels may account for increased risk of SUDEP in pregnancy
14
Q
Keppra and pregnancy
A
Increased renal clearance in 2nd and 3rd trimester
15
Q
Valproate and foetal outcomes
A
Neutral tube defects, hypospadias
Low IQ
ASD
16
Q
Lamotrigine rash
A
Most common in young
Influenced by dose and rate of drug introduction
17
Q
Valproate and lamotrigine
A
Valproate prolongs lamotrigine half-life
-Increased risk of rash and toxicity
18
Q
Carbemazepine and rash
A
Can cause SJS/TEN
Linked to HLA-B1502
-Greatest risk in Han Chinese
-Screening for all patients with Asian ancenstry
-Association weak for other AEDs
-Also applies to oxcarbazepine and esilcarbazepine
19
Q
Status epilepticus management
A
IM midazolam/ IV loraz/clonaz first line
Keppra, phenytoin, sodium valproate second line
20
Q
Indications for CBD in epilepsy
A
Dravet syndrome
Lennox-Gastaut syndrome - reduction in drop attacks
21
Q
Dravet syndrome
A
Severe treatment refractory epilepsy
Na+ channel gene mutation - SCN1A
Normal development until onset of seizures
High status epilepticus and sudden death risk
22
Q
SUDEP risk factors
A
Male
Young
Non-compliance
Poorly controlled epilepsy
Sleeping prone
Sleeping alone
23
Q
AEDs and bones
A
2-6x osteoporosis risk
Phenytoin and phenobarbital independent risk factors
Longer duration –> increased risk
Accelerated metabolism of Vitamin D and lower estradiol levels
24
Q
Parkinsons Disease risk factors
A
Age
Pesticide exposure
Farmers
Higher levels of education
History of TBI
Low sunlight/Vit D
Melanoma (shared genetic predisposition)
Genetics - PARK genes
25
Parkinsons disease protective risk factors
Smoking
Artistic occupation
26
PD Pathogenesis
a-synuclein key protein - normally soluble though prone to mutate and form insoluble species. Toxic to neurons.
Lewy bodies - pathological hallmark of P.D. Made up of a-synuclein and 90 other proteins. Found in substantial nigra
Braak staging - Lewy bodies start in dorsal motor nucleus of vagus nerve and then spread into other nuclei inc. SN then cortex
27
PD pre-motor features
Constipation
REM sleep behavioural disorder (violent thrashing, vocalisations)
Hyposmia/depression
28
REM Sleep behavioural disorder
If <40 years old - commonly due to antidepressants
If >40 years old - almost always a prodrome of a-synuclein neurodegeneration. 10% convert per year to PD/LBD/MSA
29
Management of REM sleep behavioural disorder
Stop antidepressant
Melatonin (high doses)
Clonazepam
Acetylcholinesterase inhibitor
30
Motor features of PD
MUST HAVE BRADYKINESIA
and at least one of
-Rigidity
-4 to 6Hz resting tremor
-Postural instability
31
Differentiating features of Parkinson-like conditions and PD
Less response to levodopa
Symmetric at onset
Rest tremor not prominent
Rapidly progressive
32
MRI signs of Parkinsons-like conditions
Hot cross bun sign in pons = MSA
Hummingbird sign in midbrain = PSP
Mickey Mouse sign in midbrain = PSP
Face of giant panda = Wilsons disease
Loss of swallow-tail sign = PD
33
PD treatment
Commence when functionally disabled
If <60 can start dopamine agonist or MAOI, then progress to levodopa
34
Motor fluctuations in PD
After about 5 years get wearing off, delayed on.
Dyskinesias after 10 years, severe if young age
Related to severity of disease, duration of disease, dose and duration of L dopa exposure, age of onset
35
Dopamine agonist side effects
Neuropsychiatric (cautious if >70)
Impulse control disorders (50% at 5 years)
Sleepiness
36
Managing wearing off
Add COMT, dopamine agonist, MAOI
All increase neuropsychiatric side effects
37
Treating dyskinesias
Amantadine
Other options inc. surgery, clozapine
38
Surgery in PD
Good for motor symptoms
Only if has previously shown to respond to L dopa
Speech, postural instability, freezing, cognition continue to deteriorate
Dysarthria and eyelid opening common side effects
39
PD and dementia
Lewy bodies spread to involve cortex
Key features:
-Decreased cognition (attention, executive, visual perception)
and 2/3 of:
1. Visual hallucinations (small people, animals, insects)
2. Fluctuations (staring spells, alertness, confusion)
3. P.E
40
Managing dementia in PD
Stop non L-dopa meds
Donepezil/rivastigmine improve hallucinations, psychiatric, cognition
Clozapine or quetiapine for hallucinations/paranoia
41
Visual hallucinations in PD
First sign of advanced disease
Precede death by 5 years
42
Spinocerebellar atrophy
Autosomal dominant
Assoc. with ophthalmoplegia, optic atrophy, Parkinsonism, chorea, tremor, dementia
Often present in middle age
Trinucleotide (CAG) repeats
43
Friedrich's ataxia
Ataxia <20 years old
PN, CST, HOCM, DM, Scoliosis
D.T expanding triple repeat encoding for frataxin
44
Ataxic telangectasia syndrome
Ataxia in early childhood
Cognitive decline in teens
Telangiectasia of conjunctiva
Decreased Ig levels
High leukaemia/lymphoma risk
High aFP
45
Fragile X associated tremor ataxic syndrome
Fragile x syndrome = >200 repeats in FMR1 gene
Pre-mutation 50-200 repeats causes FXTAS
-Usually older males
-Late onset ataxia with postural tremor
-Executive deficits, Parkinsonism, neuropathies common
-Do genetic tests in men >50 with ataxia and tremor
46
Imaging finding in FXTAS
MRI increased T2 signal in the cerebellar peduncles
Highly specific
47
Huntingtons disease
AD, chromosome 4, HTT gene, CAG repeats
Mean onset 45, survival 18 years
Repeats
10-26: normal
27-35: No HD, but expansion in future generations
36-40: reduced penetrance
40+: HD full penetrance
48
Huntingtons disease key features
Three domains: Motor, psych and cognitive
Motor: Chorea, impersistence (cannot sustain tongue protrusion)
Psych: depression, anxiety, apathy
Cognitive: depression, impulsive, personality change, social withdrawal
49
Westphal variant
Juvenile onset HD
50
Progressive supra nuclear palsy features, pathology, MRI changes and treatment/prognosis
Key features
Supranuclear palsy (decreased blink rate, overactive frontalis - staring gaze, slowed vertical saccades, downgaze palsy a late sign)
Postural instability
Dementia
Pathology: Tau-opathy
MRI: Hummingbird and Mickey Mouse sign in midbrain with atrophy
20% respond to levodopa
Death within 5-8 years
51
Multi-system atrophy pathology, key features
a-synuclein disorder
Disease onset in 60s
Triad of:
1. Very early autonomic failure
2. Parkinsonism
3. Cerebellar signs
Can have REM sleep disorder, erectile/urinary dysfunction
52
Restless legs management
L dopa
Pramipexole
Gabapentin/pregabalin
Iron supplementation if iron <75
53
Serotonin syndrome presentation
Mental status change
Neuromuscular activity (Hyperreflexia, clonus and rigidity in LL)
Autonomic hyperactivity
54
Drugs implicated in serotonin syndrome
SSRI, SNRI, TCA, MAO, Opioids
55
Neuroleptic malignant syndrome
Secondary to antipsychotic drugs
Triad of
1. Autonomic failure
2. Altered conscious state
3. Extrapyramidal signs
Clinically: lead pipe rigidity and Parkinsonism
Ck elevated
56
Wallerian degeneration of motor and sensory nerves timeframe
Motor = day 3-7 (don't do NCS prior to day 7)
Sensory = day 6-10
57
MND clinical features
Age of onset 55
Linear progressive muscle weakness, atrophy, fasciculations, spasticity
Sparing of eye movements, bowel and bladder
Tongue fasciculations
Split and syndrome
58
MND variants
ALS: Mixed UMN and LMN
SMA: 10%, predominant LMN
PLS: 25%, predominant UMN - better prognosis
Progressive bulbar palsy
59
MND treatment
Riluzole - extends survival by 3-6 months
CPAP
PEG feeding
60
ALS-FTD overlap
Genes that present in both
TDP43 and C9ORF72
61
MND EMG findings
Acute + chronic denervation and reservation
Fasciculations in chronic denervation areas
Positive sharp waves
62
Mutlifocal motor neuropathy with conduction block features
May clinically resemble MND however is a demyelinating disease
UL > LL
Wrist drop common
Age <45
Weakness > atrophy
Peripheral nerve pattern weakness rather than regional like MND
Absent CN or UMN signs
Decreased or absent reflexes
IgM anti- GM1 antibodies in 80%
63
Treatment of multifocal motor neuropathy with conduction block
IVIG
Cyclophosphamide
PRED CAN WORSEN
Plex
Rituximab
64
CMT disease key features
Onset 10-20
Distal. Autonomic and CNs spared
Decreased sensation, no positive sensory symptoms
Pes cavus + striking calf trophy
PMP-22 gene most commonly implicated
Onion bulbs on histology
65
Causes of mononeuritis multiplex
DM
Infections (leprosy, HIV)
Arteritis (CTD, vasculitis)
Trauma
Sarcoid
Malignancy
66
Guillain-Barre syndrome presentation
Median age 40, M>F
Symmetric ascending weakness starting in lower limbs, ascending to UL and CNs
can have tingling, burning, pins and needles before motor symptoms
Sensory loss delayed
Hyporeflexia and areflexia
Nadir by 2-4 weeks
Dysautonomia in 2/3rds
severe radicular lumbar pain in 2/3rds
67
Guillain-barre synderme pro-drome
2/3rds have preceding event
Camplyobacter jejune 32%
EBV
CMV
Mycoplasma
Vaccines/COVID
68
Guillain-barre syndrome pathogenesis
Acute, demyelinating autoimmune neuropathy
Humorally mediated rather than T cell
69
Guillain-barre syndrome investigations
Blood: elevated LFTs + CK
CSF: Albuminocytologic dissociation - low WCC high protein
FVC: <1L go to ICU
NCS: Sural nerve always preserved. Prolonged F-wave latency may be only early sign
70
Management of Guillain Barre syndrome
NO STEROIDS
PLEX or IVIg - not both
Give within 2 weeks of onset
PLEX has no benefit if given after IVIg
71
Guillain-barre poor prognostic factors and prognosis
Older, early ventilation, rapid progression, low CMAP amplitudes <20%, denervation on EMG, diarrhoea illness prior
95% have monophonic course
5% recurrence
10-20% require ventilation
5% die
72
Miller Fisher syndrome antibodies and presentation
Variant of GBS
GQ1b antibodies
Triad of:
1. External ophthalmoplegia
2. Ataxia
3. Areflexia
73
CIDP
Chronic form of AIDP
Nadir of symptoms >8 weeks
Similar muscle/sensory involvement to GBS, LL predominant
Can be chronic or relapsing remitting
CAN give steroids + steroid spring agents, IVIg monthly +/- PLEX
74
Myasthenia Gravis epidemilogy and presentation
if <40 F>M, if 40-50 M=F, if>50 M>F
Ocular symptoms most common presenting symptom: ptosis and diplopia
Generalised weakness, fatigable, 90% involve extra ocular muscles. Pupils spared
Associated with thymoma (15%) and thymic hyperplasia (65%)
Minimal atrophy
Reflexes preserved
75
Myasthenia gravis diagnosis
1. 85% with generalised have AChR antibodies, 50% of ocular will have AChR antibodies
6-10% are MuSK positive (non white, young, female, generalised MG)
2. Tensilon test (edrophonium) ACH inhibitor - assess for clinical worsening
3. Ice pack test
4. NCS/EMG - normal until repetitive stimulation - decrease in CMAP by 10% is diagnostic
5. CT Chest for thymoma
6. TFTs - autoimmune thyroid disease commonly associated
76
MuSK positive myasthenia
Atypical presentations
Non white, young, female, generalised M.G
Increased bulbar and respiratory involvement
PLEX works better than IVIg
Less response to cholinesterase inhibitor
Repsond to ritux
77
Treatment of myasthenia gravis
Pyridostigimine (cholinesterase inhibitor)
Steroids - can decrease risk of progression to generalised from ocular. Some get worse initially before improving
Steroid sparing agents
IVIG/PLEX
Single dose ritux
Thymectomy if thymoma
If hyperplasia, benefit of surgery in AChR Ab positive generalised MG
78
Myasthenia crisis
Severe weakness with respiratory failure
Intubate early
Avoid aminoglycosides, fluoroquinolone, beta blockers, CCBs and lithium
79
Myasthenia gravis and pregnancy
1/3rd will have exacerbation of symptoms in 1st trimester or post partum
Can be sudden and severe post-partum
Avoid MMF as teratogenic, can have prednisolone, IVIG, PLEX
80
Myasthenia gravis prognosis
15% treatment refractory
<5% die
Exacerbations frequent early in disease
81
Lambert-Eaton myasthenia syndrome
Paraneoplastic esp. SCLC
LL proximal weakness, ptosis but no ophthalmoplegia, facial weakness or bulbar involvement
Poor response to cholinesterase inhibitors
Antibody to pre-synaptic voltage gated calcium channel in 85-90%
PLEX, pred, guanidine, aza, diaminopyridine
82
Ipsilateral sensory pain and temp of face, ipsilateral horners, contralateral pain and temp loss in extremities
Lateral medullary syndrome (Wallenberg)
PICA infarct
83
Dominant parietal lobe
Gerstmann syndrome - angular gyrus
Agraphia (without Alexia - can copy)
Acalculia
Left-right disorientation
Finger agnosia
84
Ipsilateral 3rd nerve palsy
Contralateral weakness
Weber syndrome
Midbrain infarct
85
MELAS
Myopathy, encephalopathy, lactic acidosis and stroke-like episodes
High lactate to pyruvate ratio
Proximal muscles weakness and hypotonia, seizures and stroke-like episodes
Mitochondrial inheritance
86
RCVS key features
Recurrent thunderclap headaches
Hx of meth/marajuana
Due to vasospasm
Treat with verapamil
87
Ipsilateral hypoglossal nerve
Contralateral hemiparesis
Contralateral leminiscal sensory loss
Medial medulla
Vertebral artery
88
Botulism presentation
DESCENDING muscle weakness
CN --> UL --> LL
Respiratory muscle weakness
89
Loss of voluntary eye movements but eye reflexes intact
Asimultagnosia (inability to understand visual objects)
Balint syndrome
Bilateral PCA stroke
90
CVST epidemiology and risk factors
7:100,000 during pregnancy
Risk with hormonal therapy and post-partum
F>M
Other RF: obesity, thrombophilia, local infections, chronic inflammatory diseases, malignancy
91
CVST presentation
Headache
Visual changes/papilloedema
Focal neurology
Seizures - 33%
Encephalopathy in elderly
92
CVST management
Heparin/clexane then DOAC
Fibrinolysis/clot retrieval -minimal evidence, only if very severe
Hemicraniectomy
If occurs with pregnancy, increased recurrence risk with next pregnancy, may need prophylactic anticoagulation
93
Non-dominant parietal lobe
Constructional/dressing apraxia
Anosognosia (unaware of deficit)
Dysarthria, not dysphasia
Topographic memory loss - lost in space
94
Temporal lobe signs
Memory
Emotional and behavioural control
Prosopagnosia (inability to recognise faces)
Wernicke's aphasia
95
Frontal lobe signs
Primitive reflexes
personality change
primary motor cortex
Brocas aphasia
Anosmia
Gait apraxia
96
Brown-sequard syndrome
Loss of motor and dorsal column on ipsilateral side
Loss of pain and temp on contralateral side (one to two segments below)
97
Central cord syndrome
Bilateral loss of pain and temp at level of lesion only initially
As lesion gets bigger, affects anterior horn cells causing LMN below, then UMN below, and pain and temp below
98
Anterior cord syndrome
Everything below except dorsal columns
Usually ischaemic occlusion of anterior spinal artery
99
posterior cord syndrome
Just loss of dorsal column below lesion
Rare as two posterior spinal arteries
Can be demyelination, nutritional, genetic
100
Wernickes triad
1. Encephalopathy
2. Oculomotor dysfunction (nystagmus, lateral rectus palsy)
3. Gait apraxia
101
Wernickes/Korsakoff imaging findings
Atrophy of mamillary bodies chronically
Lesions in Wernickes symmetric and surround the third ventricle, aqueduct, fourth ventricle
102
MS epidemiology and genetics
Young women 20-40
RFs: caucasian, female, high latitude residence, inadequate sleep in adolescence, decreased Vit D, smoking, obesity
HLADRB1 15:01 confers highest genetic risk
99% are EMV Ab positive
-link to response to EMV antigen EBV NA1
103
Acute MS plaque
Indistinct margin
Inflammatory cells around vessel in a 'perivascular cuff'
Oedema and demyelination
Oligodendrocye and axonal loss variable
104
Chronic MS plaque
Distinct margin
Hypocellular core, enlarged perivascular spaces
Loss of myelin and glial scarring prominent
105
Grey matter plaques in MS significance
Correlate with progressive disease and cognitive dysfunction
106
Investigations in MS
Imaging: T2 on MRI
Juxtacortical
Periventricular
Infratentorial
Spinal cord (<2 segments length)
CSF: Oligoclonal bands in CSF ONLY
VEP: records action of optic nerve
107
Poor prognostic factors in MS
Frequent relapses in first 2 years
Short interval between first 2 relapses
Rapid early disability progression
High lesion load
Cerebral atrophy
Male
Later age of onset
108
Genetic variant that increases MS severity
RS10191329 in the DYSZNF638 locus
Decreases time to walking aid by 3.7 years
109
Protective factor in MS
Higher educational attainment
110
Natalizumab
Monoclonal Ab against Alpha-4 intern
Monthly IV
SE: Inc. herpes virus reactivation
PML
-Any prior immunosuppression - high risk
->2 years on natalizumab risk increases
-JCV index (level of positivity)
-6 weekly instead of 4 weekly dosing decreases risk
-Repeat JC virus serology 6 monthly if initially seronegative - 5% convert per year
111
Natalizumab and a foetus
Fetal haematological abnormalities if continued in 3rd trimester
If high relapse risk, continue until 3rd tm
112
Alemtuzumab
Anti-CD52 found on all differentiated lymphocytes and monocytes
Selective immune re-constitution therapy
- B cells weeks to months
- CD8 T cells several years
- CD4 T cells up to 5 years
SE: infection risk
Secondary autoimmunity - AI thyroid disease in 30%
Blood test monitoring for 5 years
113
Ocrelizumab
Anti-CD20
Approved for PPMS
IV 6 monthly
SE: infection risk (Esp. hep b reactivation)
114
Cladribine
SIRT
SE: Lymphopenia
115
PML treatment
Pembrolizumab
116
Fingolimod
S-1-P receptor inhibitor - stops lymphocytes from leaving lymph nodes. Also affects astrocytes
Daily oral table (first oral approved for MS)
SE: first dose bradycardia - needs monitoring
LFT derangement, lymphopenia
117
Ozanimod
S-1-P receptor inhibitor
Less cardiac side effects than fingolimod, doesn't need monitoring, same efficacy
118
Dimethyl fumarate
Modulates anti-oxidative pathways via activation of NRF2
BD PO tablet
SE: Flushing (very common)
GIT upset (30%)
119
Diroximel fumarate
Same active ingredient as dimethyl fumarate with similar efficacy but lower GI side effects
120
Teriflunomide
Inhibits dihydroorotate dehydrogenase and interferes with pryimidine synthesis --> effects rapidly dividing cells like activated lymphocytes
SE: hepatotoxic, hair thinning
121
Glatiramer acetate
Polypeptide similar to myelin, unclear MOA
SC injections
122
Interferon Beta 1a and 1b
Diverts immune system away from pro-inflammatory (Th1 and Th17) to anti-inflammatory (Th2) pathway
SE: Flu-like symptoms
depression
LFT derangement
123
SCT for MS - what doesn't improve
Cerebral atrophy continues to worsen
124
Pregnancy and MS
MS does not affect fertility
Decreased events in pregnancy, but increased in 3 months post-partum
Exclusive breastfeeding provides 30-50% reduction in activity post-partum
125
Safest MS drugs to use in pregnancy
Glatiramer, dimethyl fumarate
126
Neuromyelitis optica spectrum disease pathogenesis and presentation
Demyelination in optic nerves and spinal cord. Due to AQP4 antibodies binding to water channels on astrocytes causing complement dependent toxicity
127
Imaging in NMOSD
Longitudinally extensive spinal cord lesion (LETM) >2 segments
Long optic nerve lesion (posterior/optic chiasm)
Dorsal medulla lesions (area postrema)
Hypothalamus/thalamus lesions
128
NMOSD presentations
Optic neuritis
Acute myelitis
Area postrema syndrome (intractable hiccups, nausea, vomiting)
Acute brainstem syndrome
Symptomatic cerebral syndrome with NMOSD-typical imaging
129
Management of NMOSD
Most MS meds will worsen
Treat with IV methyl pred then oral prednisone wean over months +/- PLEX acutely
MMF/Aza
Ritux off label
IL-6 blockade emerging
130
Myelin oligodendrocyte glycoprotein antibody disease (MOG)
MOG is exclusively expressed on myelin and oligodendrocytes in CNS
Anti-MOG ab in 25% of paediatric first demyelinating events, and 50% of seronegative NMOSD
Presentation: Bilateral (consecutive) optic neuritis - very severe
Long spinal cord lesions and brainstem lesiosn
Encephalitis, seizures, aseptic meningitis, PNS demyelination
Longer time between relapses compared to NMOSD
Manage with steroids - good recovery of vision
If relapsing - MMF/Aza/ritux
131
Young man with Anti-Ma2 encephalitis
High likelihood of testicular germ cell tumour
132
Key features of corticobasal degeneration
ALIEN HAND SYNDROME
Ideomotor apraxia of the hand
133
Dorsal root gangliopathy features and causes
Sensory gone everywhere
Sjogrens, B6 toxicity, paraneoplastic (Hu)
134
Anti-LGI-1 encephalitis
Limbic encephalitis
FACIOBRACHIAL seizures
Medial temporal lobe affected
135
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