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Flashcards in General neurology Deck (185):
1

What % of those with ALS have FTD?

13%

2

What is the major genetic cause shared by ALS and FTD?

C9orf72

3

TDP-43 is found in which diseases?

FTD and ALS

4

What is Onuf's nucleus responsible for?

Sphincter control

5

How do triptans work (in migraine)?

Activators of 5-HT receptors, 1B/1D/1F

6

What options are available for migraine prophylaxis?

Amitriptyline, nortriptyline, pizotifen, candesartan, propranolol, sodium valproate, topiramate, verapamil

7

Which nerves pass through the jugular foramen?

IX, X, XI

8

What passes through the cavernous sinus?

CN III, IV, V1, V2, VI

9

What causes autonomic dysreflexia?

Spinal cord injuries above T6.
- HTN and bradycardia
- Below T6 allows splanchnic innervation and therefore dilatation to bring down BP

10

What are the common side effects of phenytoin?

Gingival hyperplasia, hirsutism, rash, folic acid depletion, osteoporosis, cerebellar signs

11

What is the prognosis at diagnosis?

3-5 years

12

What does reinnervation look like on EMG?

High amplitude CMAPs

13

How is conduction block defined on Nerve Conduction Studies?


A reduction in CMAP area/amplitude of at least 20% compared with distal CMAP area/amplitude.
The duration of the proximal CMAP should not increase by >20% (see temporal dispersion)

14

Which antibody is multifocal motor neuropathy associated with?

anti-GM1

15

How is primary lateral sclerosis distinguishable?

Affects upper motor neurons only

16

How is progressive muscular atrophy distinguishable?

Affects lower motor neurons only

17

What are the 2 most commonly found mutations in ALS?

C9orf72 and SOD1

18

How is EPHA4 implicated in prognosis in ALS?

Lower EPHA4 = longer survival

19

Which exposure is the strongest risk factor for ALS?

Military service.

20

How does riluzole work in ALS?

Suppresses excessive motor neuronal firing

21

How does edaravone work in ALS?

Suppresses oxidative stress

22

What is the treatment for cluster headaches?

Acute: 100% O2, triptan
- Severe refractory => indomethacin or dihydroergotamine
Bridging: prednisone or occipital nerve block with methylpred
Prophylactic: Verapamil

23

What is the genetic mutation responsible for Wilson's disease?

ATP7B mutation on chromosome 13 (autosomal recessive)

24

Which mutation is associated with the highest risk of multiple sclerosis?

HLA DRB1*1501

Other risk = *0801

25

What is first line treatment in primary progressive MS and what is its mechanism of action?

Ocrelizumab - fully humanised anti-CD20 that suppresses B cell

26

What does downbeating nystagmus represent?

Lesion in the foramen magnum

27

What does upbeating nystagmus represent?

Lesion in the midbrain or floor of the fourth ventricle

28

How do you distinguish between myositis and myopathy on EMG?

Spontaneous firing in myositis, but not myopathy

29

What are the causes of predominantly sensory neuropathy?

Diabetes
B12 deficiency
Uraemia
HIV
Malignancy
Sjogren's
Hereditary sensory and autonomic neuropathy
Amyloid

30

What are the causes of predominantly motor neuropathy?

AIDP
Acute motor axonal neuropathy
Hereditary motor and sensory neuropathy
Lead
Porphyria
Multifocal motor neuropathy
Diphtheria
Diabetic
Amyloid

31

Painful neuropathy

EtOH
Diabetes
Cryoglobulinaemia
HIV
Paraneoplastic
GBS
B6 toxicity
Amyloid

32

Which antibodies may be positive in GBS?

GM1, GM2 and GD1

33

What is the triad found in Miller-Fisher and what is the antibody associated with it?

Ataxia, ophthalmoplegia and areflexia
Anti-GQ1

34

What does CSF show in GBS and CIDP?

Albuminocytologic dissociation - high protein / low cells

35

What is the treatment for GBS?

IVIG or plasma exchange

36

What are the treatment options for CIDP?

Steroids
IVIG or plasma exchange
Steroid-sparing agents: AZA or MMF (faster action)

37

In which variant of CIDP is asymmetry classic?

MADSAM

38

What is POEMS? Which serum level is diagnostic?

Polyneuropathy
Organomegaly
Endocrinopathy
Monoclonal protein
Skin changes

VEGF level is doagnostic

39

What pedal changes would be seen in Charcot-Marie-Tooth disease?

Pes cavus
Hammer toes

40

What is the mutation responsible for hereditary sensitivity to pressure palsies (HSPP)?

PMP22
- Prolonged distal motor latencies

41

What does nerve biopsy show in Charcot-Marie-Tooth disease?

Onion bulbs

42

Where is a biopsy taken form for diagnosis of amyloidosis? What does it show?

Fat pad
Apple-green birefringence on congo red stain

43

What are the treatment options for diabetic neuropathy?

1 Amitriptyline,
2 duloxetine or pregabalin or gabapentin

44

What are the features of Morvan Syndrome and which antibody is implicated?

Features:
- Fasciculations
- Paraesthesia
- Thymoma
- Encephalophathy
- Neuromyotonia

Antibody:
- Caspr-2 => directed at Voltage-gated K channels

45

Which antibodies are implicated in 60% of cases of stiff person syndrome?

Anti-GAD

46

What antibodies are associated with myasthenia gravis?

ACh receptor Ab
- 80-90% sensitive
MuSK Ab
- positive in 40% of AChR-negative patients.
- more severe weakness, not affecting eyes or limbs
- not associated with thymic disease.
LRP4 Ab
- mild-moderate disease
- not associated with thymic disease.
Anti-striated muscle Ab
- positive in 90% of thymomas
Ryanodine receptor Ab
- positive in 70% of thymomas with MG
- marker for severe disease
Titin Ab (in addition to ACh R Ab)
- thymoma and late-onset MG
Agrin Ab
- poor sensitivity but specific for MG

47

What should be specifically checked for on examination in myasthenia gravis?

- Sustained upward gaze - weakness of eyelid elevators and oculomotor muscles
- Peek sign - eyelids separate after 30sec of closing, and sclera is visible.
- Dysarthria - palate weakness
- Dysphonia on counting - bulbar weakness
- Smiling causes snarling expression
- Neck flexion weakness
- Flap 1 arm then test muscle strength together - asymmetrical due to fatigue of one arm
- Improvement of ptosis with ice cube application

48

What does EMG show in myaesthenia gravis?

Repetitive stimulation shows progressive decrease in amplitude of action potentials
Needle examination - motor unit potential variation and, sometimes, fibrillation potentials and myopathic changes
Single-fibre EMG - increased jitter (variable interpotential interval). 80% sensitive.

49

What other investigations should be performed in myaesthenia gravis?

Thymoma search - CXR, chest CT or MRI
Respiratory function tests - weakness in muscles of respiration

50

What is myasthenic crisis and how is it treated?

Crisis involves respiratory weakness causing respiratory failure. Often caused by an infection.

Treatment: Antibacterial
IVIG or plasma exchange

51

What is first line treatment for myaesthenia gravis?

Acetylcholinesterases - pyridostigmine
K supplements and K-sparing diuretics may improve symptoms but are rarely used

52

What if acetylcholinesterase inhibitors fail in myaesthenia gravis?

Steroids - may worsen symptoms and therefore should be monitored closely during initiation.
Immunosuppressants next line - azathioprine may be used as steroid-sparing agent, however should never be used as monotherapy.
Rituximab in desperate cases

53

What % of myasthenia gravis have isolated ocular signs?

15%

54

Which antibodies are implicated in isolated ocular myasthenia gravis?

Acetylcholine and LRP4 (not MuSK)

55

What autoimmune diseases are often associated with myasthenia gravis?

Thyroiditis (most commonly)
SLE and RA
Polymyositis
NMO
ALS

56

Kv1.4, ryanodine and titin antibodies in myasthenia gravis are associated with which coexisting cardiac condition?

Myocarditis

57

What is the most effective cholinesterase inhibitor used in myasthenia gravis?
Which subpopulation is it less effective in?

Pyridostigmine
Less effective in MuSK positive patients

58

What is second line Rx for myasthenia gravis?
Third? Fourth?

2nd - Prednisone + AZA
3rd - Mycophenolate (mild) or rituximab (moderate)
4th - Methotrexate, cyclosporin, tacrolimus

59

How is myasthenic crisis treated?

IVIG or plasmapheresis

60

Which myasthenia patients should have a thymectomy?

Recommended in:
- Those with thymomas
- Early-onset myasthenia gravis
- Generalised myasthenia gravis and ACh receptor Abs. 70% of these show improvement after thymectomy.
- Seronegative MG with generalised disease and biomarkers similar to early-onset MG

Not recommended in:
- MuSK or LRP4 Ab positive
- Ocular MG
- Seronegative MG

61

Which medications may precipitate a myasthenic crisis?

Aminoglycosides
Tetracyclines
Fluoroquinolones
Macrolides
Muscle relaxants
Beta blockers
Calcium channel blockers
Botox
Iodine
Penicillamine

62

What side effects are associated with pyridostigmine?

Abdominal cramps, diarrhoea

63

Which features of Lambert-Eaton Myasthenic Syndrome distinguish it from myasthenia gravis?

- No ophthalmoparesis, facial weakness or bulbar involvement
- Poor response to cholinesterase inhibitors
- Autonomic symptoms
- Reduced deep tendon reflexes
- Increase in size of CMAP on repetitive nerve stimulation

64

Anti-Hu antibodies are associated most strongly with which cancer?
What paraneoplastic syndromes are they associated with?

- Lung cancer (mostly small cell)
- Encephalomyelitis, limbic encephalitis, brain stem encephalitis, cerebellar degeneration, multi-segmental myelitis, sensory neuronopathy, sensorimotor neuronopathy, autonomic neuronopathy

65

Anti-Yo antibodies are associated with which cancers?
Which paraneoplastic syndrome are they associated with?

- Ovarian and breast
- Subacute cerebellar degeneration

66

Anti-CRMP5 antibodies are associated with which cancers?

- Small cell lung cancer, thymoma

67

Anti-Ma2 antibodies are associated with which cancers?

- Testicular cancer

68

Anti-Ri antibodies are associated with which cancers? Which syndrome is most associated with it?

- Breast, ovarian, SCLC
- Associated with opsoclonus-myoclonus syndrome

69

Anti-amphiphysin antibodies are associated with which cancers?
Which paraneoplastic syndrome are they associated with?

- Breast, SCLC
- Limbic encephalitis, stiff person syndrome

70

Lhermitte's sign is suggestive of a lesion in which part of the nervous system?

Dorsal columns of C-spine or caudal medulla

71

Which antibodies in neuromyelitis optica are associated moreso with optic neuritis than myelitis?

MOG antibodies
- Also found in ADEM

72

What is the order of progression in multiple sclerosis medications?

1. Glatiramer acetate, beta-interferon
2. Daclizumab, teriflunomide
3. Fingolimod, dimethyl fumarate
4. Natalizumab, alemtuzumab
5. Autologous HSCT

73

What is the mechanism of action of fingolimod?

- S1P receptor agonist. Causes
- Prevention of lymphocytes from migrating out of lymph nodes

74

What side effects are associated with alemtuzumab?

Autoimmune thyroid disease
Immune thrombotic thrombocytopenia
Membranous GN and anti-GBM disease

75

What does CADASIL stand for and what is the mutation responsible for it?

CADASIL = Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leucoencephalopathy

Notch 3 mutation - chromosome 19q12

76

Which 2 areas of the brain are classically involved in CADASIL?

Anterior temporal lobes
External capsule

77

What is the mechanism of action of glatiramer?

- Competition with myelin antigens for binding to T cells
- Induction of Th2 suppressor cells that downregulate inflammation

78

What is the mechanism of action of alemtuzumab?

CD52 mAb - stimulates antigen dependent cell-mediated cytotoxicity

79

What side effects of dimethyl fumarate should be monitored for?

Lymphopenia
LFT derangement

80

What side effects are associated with fingolimod?

Herpes infections
Macular oedema
Bradycardia

81

What are the 3 main clinical presentations associated with neuromyelitis optica? What are 3 less common presentations?

Most common:
- Optic neuritis
- Longitudinally extensive transverse myelitis
- Area postrema syndrome (nausea/vomiting/hiccups)

Less common:
- Other brainstem lesion
- Narcolepsy or diencephalic syndrome with MRI lesion
- Symptomatic cerebral syndrome with MRI lesion

82

What is the treatment for neuromyelitis optica?

Plasma exchange

83

What does dimethyl fumarate act on to down-regulate inflammation?

Nrf2

84

How does teriflunomide act?

Inhibition of DHODH, which is necessary for pyimidine synthesis in prolferating lymphocytes.

85

What are the risk factors for Sudden Unexplained Death in EPilepsy (SUDEP)?

Multiple antiepileptics
Nocturnal seizures
Long duration of therapy
Early onset epilepsy
Male

86

What is the approximate incidence of SUDEP in epileptic adults?

1 in 1000

87

What is the most common genetic generalised epilepsy?
What are the typical features of it?

Juvenile myoclonic epilepsy
- Typical absence seizures, usually precede myoclonic jerks by 1-9 years
- Myoclonic jerks on wakening
- Generalised tonic clonic seizures develop months to years after myoclonic jerks
- Very sensitive to EtOH and sleep deprivation
- Autosomal dominant

88

What is first line treatment for juvenile myoclonic epilepsy?

Sodium valproate

89

What is the most commonly affected area in temporal lobe epilepsy?

Mesial temporal lobe (hippocampus) - 65%

90

During which period of sleep do sleep-related hypermotor epileptic seizures usually occur?

Non-REM

91

What is the classic finding in GLUT1 deficiency and how is it treated?

Low CSF glucose
Treat with ketogenic diet

92

What is the classic finding in GLUT 2 deficiency?

Paroxysmal exercise-induced dystonia

93

Which 2 HLA genes are associated with Stevens Johnson Syndrome?

HLA-B*1502: Taiwan
HLA-A*3101: Europeans and Japanese

94

Which form of epilepsy is anti-GAD antibody associated with?

Temporal lobe epilepsy

95

What does levetiracetam bind to?

Presynaptic SVA2

96

Where do gabapentin and pregabalin act on?

Post-synaptic calcium channels

97

What are the 2 sites of action of lacosamide?

CRMP-2 pathway (pre-synaptic)
Na channel inactivation (pre-synaptic)

98

What is the primary site of lamotrigine?

Na channels

99

Which antiepileptic is 1st line in absence seizures?

Ethosuxamide

100

What % of patients become seizure-free after their first antiepileptic agent?

47%

101

What happens in coadministration of COCP and lamotrigine?

Lamotrigine metabolism increased by COCP - dose must be increased

102

What is the main teratogenic risk involved with sodium valproate and carbamazepine?

Spina bifida

103

What side effects are associated with sodium valproate?

Weight gain
Drowsiness
Alopecia
Liver dysfunction
Tremor
PCOS

104

What side effects are associated with carbamazepine?

SIADH
Drowsiness
OP

105

What side effects are associated with phenytoin?

Gum hypertrophy
Coarsening of facial features
Hirsutism
OP
Cerebellar atrophy

106

What side effects are associated with topiramate?

Weight loss
Renal calculi
Word-finding difficulties
Suicidality

107

What is the most effective treatment in mesial temporal lobe epilepsy?

Temporal lobectomy

108

What are the first line antidepressants for epileptics?

Citalopram and sertraline

109

What are the 2 main genetic forms of Parkinson's Disease?

Parkin, DJ-1 (recessive) also PINK1
Lrrk2, SNCA (Dominant)

110

Name the 3 main synucleinopathies?

Parkinson's Disease
Lewy Body Dementia
Multiple System Atrophy

111

What is the main part of the brain affected in Parkinson's Disease?

Substantia nigra pars compacta

112

Which receptors do pramiprexole and ropinirole act on?

D2/3

113

Which receptor does rotigotine act on?
Which population are they useful in?

D2
Useful in dysphagia

114

What are the ergot-derived dopamine agonists and which receptors do they act on?

Cabergoline, pergolide
D1/2

115

What are the MAO-B inhibitors used in Parkinson's Disease?

Rasagiline and selegiline
- Reserved for late disease

116

What is the mechanism of action of apomorphine?

D2 receptor agonist

117

What is amantadine used for?

Dyskinesias in Parkinson's Disease

118

Which part of the brain is deep brain stimulation targeted at?

Subthalamic nucleus
Globus pallidus internus

119

Which antipsychotic has evidence supporting treatment of psychosis in Parkinson's Disease?

Clozapine
Trial reduction in anti-PD meds first

120

What is the first line treatment for depression in Parkinson's Disease?

Nortriptyline

121

What are the approved treatments for dementia in Parkinson's Disease?

Rivastigmine
Donepezil may be useful for hallucinations and cognitive impairment

122

What are the treatment options for REM sleep behaviour disorder?

Clonazepam
Amitriptyline

123

How do Parkinsonian tremor and essential tremor differ from each other?

PD - Rest tremor, 5Hz, asymmetrical
Essential tremor - Postural tremor, 10Hz, symmetrical

124

What is the putaminal slit sign specific for?

MSA Parkinsonian type

125

What is the classic pontine finding in multiple system atrophy - cerebellar type?

Hot cross bun type

126

How does midodrine act?

apha-1 agonism

127

What is the mechanism of action of mirabegron?

Beta3 agonism

128

What is a side effect of levodopa in MSA?

Exacerbation of orthostatic hypotension

129

What is the first eye movement to be affected in Progressive Supranuclear Palsy?

Downward gaze

130

What is the MRI brain classic finding in PSP?

Hummingbird sign - midbrain atrophy

131

What are the treatment options in PSP?

Levodopa and amantadine

132

Which Parkinsonian condition demonstrates myoclonus and limb apraxia?

Corticobasal degeneration

133

Which of the Parkinsonian syndromes has the worst median survival from diagnosis?

Corticobasal degeneration

134

What can be used to treat dystonias in corticobasal degeneration?

Botox if painful

135

What is the genetic mutation responsible for Huntington's disease?
When does it become symptomatic?

CAG triplet repeat disorder of the huntingtin gene on chromosome 4.
Symptomatic at >37 repeats

136

Which neurons are affected in Huntingtin's Disease?

GABAergic neurons

137

Which part of the brain may show atrophy in Huntington's Disease?

Caudate

138

What is the treatment for tardive dyskinesia?

Tetrabenazine, benztropine

139

Which brain structure is damaged in hemibalism?

Subthalamic nucleus

140

How does Brown-Sequard syndrome present and what is it caused by?

- Ipsilateral paralysis
- Ipsilateral vibration, proprioception and light touch discrimination
- Contralateral pain and temperature

Caused by cord hemisection.

141

What is the genetic mutation responsible for Wilson's Disease? What is its mode of inheritance?

ATP7B
Autosomal recessive

142

How is Wilson's Disease diagnosed?

Low caeruloplasmin
High urinary copper
Kayser-Fleischer rings
High copper levels on liver biopsy

143

What are the treatment options in Wilson's Disease?

Penicillamine
Trientene if intolerant of penicillamine
Levodopa

144

What is the genetic mutation responsible for Fragile X-associated tremor/ataxia syndrome (FXTAS)? What is the mode of inheritance?

CGG triplet repeat 55-200 in FMR1 gene
X-linked dominant

145

What is the classic MRI sign found in FXTAS?

Middle cerebellar peduncle sign

146

Name 3 dopamine receptor agonists approved for restless legs syndrome

Pramipexole, ropinirole, rotigotine

147

Name 5 causes of restless legs syndrome

Iron deficiency
ESRF
Pregnancy
Drug induced - metoclopramide
Multiple sclerosis
Neuropathy

148

What ar the windows for IV thrombolysis and IA thrombectomy?

thrombolysis - 4.5 hours
thrombectomy - 6 hours

149

What is the mechanism of action of idaracizumab?

Monoclonal antibody that competitively inhibits dabigatran (competes with FIIa)

150

In cervical artery dissection, is anticoagulation or antiplatelet therapy more effective?

No difference

151

What is the prefered class of antihypertensives in ischaemic stroke?

- Calcium channel blockers
- Beta blockers may increase risk of ischaemic stroke, however are indicated in concurrent ischaemic heart disease

152

When should patients be mobilised after an ischaemic stroke?

After 24 hours

153

What is the mechanism of action of evolocumab?

- PCSK9 inhibitor - increases hepatocyte LDL receptors available to degrade LDL
- PCSK9 degrades LDL receptors

154

How does amyloid angiopathy present and in which population?

Lobar, juxta-cortical haemorrhages in the elderly

155

Where do hypertensive intracerebral haemorrhages tend to present?

Putamen, thalamus, pons

156

Which levels of the Modified Rankin Scale qualify for thrombolysis?

MRS 0-2

157

Which medication should be used for DVT prophylaxis post-ischaemic stroke?

Enoxaparin (more effective than heparin in this population)

158

Which patiets with an ischaemic stroke would benefit from hemicraniectomy?

Large ischaemic MCA stroke and age<60

159

When should a NOAC be commenced post-stroke in non-valvular AF?

small stroke - day 3
moderate stroke - day 6
large stroke - day 12

160

When is TIA or stroke recurrence highest?

3 weeks to 3 months

161

What consitutes valvular atrial fibrillation

AF with the absence of mitral stenosis or mechanical heart valve

162

Which patients should have carotid endarterectomies and within what time frame?

- Treat SYMPTOMATIC carotid artery stenosis 70-99%.
- Carotid endarterectomy within 2 weeks of event

163

When should patent foramen ovale be closed?

1. PFO + atrial septal aneurysm + large shunt
2. Young patient with ambolic ischaemic stroke and no other cause identified for stroke

164

How does the OCP affect stroke risk?

Elevated risk with oestrogen but not progesterone

165

What are the 4 clinical features associated with Creutzfeldt-Jakob Disease?

Myoclonus
Visual or cerebellar disturbance
Pyramidal/extrapyramidal disturbance
Akinetic mutism

166

Which tumour are NMDA receptor antibodies associated with?

Teratoma

167

What should be tested for in hypokalaemic periodic paralysis?

Thyrotoxicosis

168

Alexia without agraphia is specific for which arterial territory?

Dominant PCA

169

What are the 4 types of Creutzfeldt-Jakob Disease?

Sporadic - most common (85%)
Iatrogenic - from dural grafts, etc
Variant - from bovine spongiform encephalopathy
Familial

170

What is the classic MRI finding in CJD?

FLAIR and DWI: Cortical ribboning and basal ganglia hyperintensity

171

What is necessary to diagnose CJD?

- Brain biopsy showing PrPsc
- PRNP gene testing must be performed to exclude familial CJD

172

What might CSF show in CJD?

- Pleocytosis (lymphocytes)
- Elevated protein
- 14-3-3 protein

173

Which muscles are affected in a deep peroneal nerve palsy? Which sensory distribution?

Muscles:
- Tibialis anterior: ankle dorsiflexion, foot eversion
- Extensor hallucis: big toe extension
- Extensor digitorum longus: lateral 4 toes extension
- Extensor digitorum brevis: big toe and medial 3 toes extension

Sensory: first dorsal webspace

174

How can an L5 nerve palsy be distinguished from common peroneal nerve palsy?

L5: Foot inversion and hip abduction affected, unlike peroneal nerve

175

How might CSF help distinguish between multiple sclerosis and neuromyelitis optica?

MS: oligoclonal bands
NMO: NO oligoclonal bands

176

What is the treatment for neuromyelitis optica?

Rituximab and MMF

177

A lesion in which vascular territory is responsible for the syndrome of alexia without agraphia?

Dominant PCA

178

What is the mechanism of action of pimavanserin and what is it used for?

Inverse agonist of 5-HT2A receptor.
Used for psychosis in Parkinson's Disease.

179

What are the first and second line treatments for trigeminal neuralgia?

1. Carbamazepine
2. Oxcarbazepine

180

What are the first and second line treatments for greater occipital neuralgia?

1. Occipital nerve block
2. Gabapentin or pregabalin

181

Which nerves are most likely to be affected by a cerebellopontine angle tumour?

V, VII, VIII

182

Which muscle flexes the distal interphalangeal joints in the fingers?

Flexor digitorum profundus

183

What is the mechanism of action of benztropine in Parkinson's Disease?

Atypical competitive inhibitor of dopamine reuptake

184

How can central retinal artery occlusion and central retinal vein occlusion be differentiated on fundoscopy?

CRAO
- Grossly swollen and pale retina
- Prominent fovea (cherry red spot)

CVRO
- Disc is massively swollen with splotches of haemorrhage and cotton wool spots

185

How does an ophthalmic artery occlusion differ on fundoscopy from central retinal artery occlusion?

Ophthalmic artery occlusion
- No cherry red spot and vision is reduced to light perception only.