Neurology Flashcards
What is pyramidal weakness
Power seen in UMN lesions
Extension weakness in UL and flexor weakness in LL
Earliest sign seen in UMN lesions
Plantars
UMN lesions initally look like LMN lesions in hyperacute stage
Lentiform nucleus includes
Globus pallidus and putamen
Frontal lobe features
Primary motor cortex - dictates movement Personality Primitive reflexes Dysphasia Expressive (dominant) Anosmia Optic nerve compression Gait apraxia (gait memory)
Parietal Lobe features
Primary sensory cortex Gerstmann syndrome Sensory, visual, spatial inattention Construction and dressing apraxia Lower Quadrantanopia
Temporal lobe features
Pimary auditory cortex
REceptive dysphasia (dominant)
MEmory loss - hippocampus and amygdala
Upper quadrantanopia
Occipital Lobe Features
Homonymous Hemianopia
Anton’s Syndrome
Alexia without agraphia
Gerstman Syndrome
Dominant angular gyrus lesion
Acalculia, graphia, L-R disorientation, fingeragnosia (ALF)
Anton’s Syndrome
Bilateral occipital cortical lesion
Cortical blindness with confabulation
PITS
Parietal inferior quadrantanopia
Temporal superior quadrantanopia
Non- fluent/Expressive/Broca’s/Transocrtical motor aphasia
Able to comprehend, paucity of words, know what they want to say, but cant
+++Frustration
Dominant frontal lobe lesion
Fluent, repetitive, wernickes, transcortical sensory aphasia
Unable to comprehend, fluent but incomprehensible speech
Like a foreign language
Dominant temporal lobe lesion
Conduction aphasia
Mix between broncas an wernickes aphasia
-Able to comprehend with elements of fluent aphasia and poor repetition
Arcuate fasciculus lesion (connection between the 2 areas)
Most important part of the internal capsule and why
Posterior limb and Genu
-Carry the corticospinal trcts and some sensory fibres
Blood supply of the internal capsule
LEnticulostriate arteries which are penetrating branches of MCA (M1)
-Common areas of atherosclerosis
Stroke of lenticulostriate arteries in internal capsule presentation
pure motor stroke
Dense weakness, nil cortical signs
Thalamus Rule of 4s: Anterior nuclei
language and memory function (frontal/temporal input)
Thalamus Rule of 4s: Lateral nuclei
motor and sensory function
Thalamus Rule of 4s: Medial nuclei
maintaining arousal and memory (midbrain)
Thalamus Rule of 4s: Posterior nuclei
visual function
Issue with bilateral thalamic lesions
significant arousal issues
Thalamic stroke classical presentation
Pure sensory loss stroke
Terminal area for all sensory nerves
Arterial supply of thalamus
PCA
Cerebellum: Vermis lesion
Truncal ataxia
Nystagmus
Cerebellum: Hemisphere lesion
Ipsilateral limb ataxia Past pointing Dysmetria Intention tremor Dysdiadokinesia Nystagmus
Brain stem Rule of 4’s
4 Cranial nerves in the medulla, pons, and above pons
4 structures in the midline beginning with M
–Motor pathway, Medial lemniscus, medial longitudinal fasciculus, motor nucleus
4 structures on the side beginning with S
–Spinocerebellar pathway, spinothalamic pathway, sensory nucleus of 5th CN, Sympathetic tract
4 motor nuclei in the midline that divide equally into 12 (3.4.6.12)
Horner’s syndrome features
miosis, ptosis, anhidrosis
Points of terminals: C8/T1, then past lung apex, then superior cervical ganglion by bifurcation of ICA and ECA where sweat gland goes with ECA, then to eye along with ICA
CN 1
Olfactory
-Smell
CN 2
Optic
-Vision, afferent pathway for pupil
CN 3
Oculomotor
- Superior, inferior, medial rectus, inferior oblique, levetor palpebrae
- Efferent pathway for pupil
CN 4
Trochlear
-Superior oblique (depression, most in adduction, and intorsion)
CN 5
Trigeminal
-Facial sensation, muscles of mastication
CN 6
Abducens
-LAteral rectus
CN 7
Facial
- Muscles of expression, stapedius
- Sensation of anterior 2/3 of tongue
CN 8
Vestibulocochlear
-Hearing and balance
CN 9
Glossopharengeal
- Sensation: middle ear, posterior 1/3 tongue
- Some swallowing
CN 10
Vagus
- Sensation of pharynx, larynx, oesphagus thoracic and abdominal viscera
- Motor: soft palate, larynx, pharynx
CN 11
Accessory
-Sternocleidomastoid, trapezius
CN 12
Hypoglossal
-Tongue movement
Medial longitudinal fasciculus connects what 2 CN nuclei?
3 and 6
INO PAthyphysiology
Problem with MLF
Want to look to one side and signal sent to CN6 nuclei but due to damage to MLF cannot send signal to contralateral eyes CN3 nuclei to look in the same direction. So one eye abducts and the other does not move
Affected side is side which eye does not move
Normal eye then gets nystagmus to catch up with affected eye
Classically due to MS, but can be due to stroke in elderly
ACA territory stroke
Leg weakness >arm weakness
Pelvic floor dysfunction
Basilar stroke
Step wise stroke progression
Usually first medullary symptoms
Then diplopia
Then lose midbrain and drop in GCS
Lacunar Stroke: Pure motor stroke
Posterior limb of internal capsule r anterior portion of pons
Lacunar stroke: Ataxic hemiparesis stroke
Posterior limb of internal capsule, basis pontis, and corona radiata
Combination of cerebellar and motor Sx
Legs>arms
Lacunar stroke: Dysarthria/clumsy hand
Basis pontis lesion
Lacunar stroke: pure sensory
Thalamic infarct
Lacunar stroke: Mixed sensorimotor
Thalamus and posterior limb of internal capsule
Spinothalmic tract synapse and decussation
1st order neuron has cell body in dorsal root ganglion.
Synapse onto 2nd order neuron in posterior horn and that nerve then crosses over to the contralateral side and synapses in the thalamus.
Decussation occurs over 2-3 segments while ascending
Posterior column synapse and decussation
1st order neuron synapses on second order neuron in the medulla
2nd order neuron is called the medial lemniscus and decussates in the medulla
Then goes to thalamus and primary sensory cortex
Corticospinal tract synapse and decussation
1st order neuron from primary motor cortex to the anterior horn with decussation at the medulla
2nd order neuron from anterior horn through anterior nerve root to destination
Brown Sequard
Ipsilateral UMN weakness below lesion
Ipsilateral vibration and proprioception impairment below lesion
Contralateral pain and temp impairment 1-2 segments below lesion
Ipsilateral LMN weakness and sensory loss AT the level of lesion
Central Cord Syndrome
Loss of pain and temp bilaterally at the level of lesion
“Suspended sensory level” “Cape/vest distribution”
Increase in size of lesion: LMN lesion at the level of lesion
Further increase in size: UMN weakness and temp and sensation loss below the lesion
Spinal cord blood supply
Anterior and posterior spinal arteries supplied by:
- Vertebral arteries of the neck
- Intercostal branches of the aorta and midthoracic region
- Great Radicular artery (of Adamkiewicz) in the lower thoracic or lumbar region
Anterior cord syndrome
Everything gone except posterior column
USually ischemic with occlusion of anterior spinal artery
Posterior cord syndrome
Only loss of dorsal column
Rarely ischemic given bilateral blood supply
Usually demyelination, nutritional, or genetic
T1
Grey is grey and white is white
Good for anatomy
T2
Grey is light
White is grey
Good for pathology
T2 Flair
Suppresses the CSF color
Grey is light and white is grey
Good for pathology
MRI DWI
For infarcts
Bright color is stroke
MRI ADC is the opposite and also good for strokes where dark color means stroke
Bloome artifact on MRI
Microhemorrhages
Contraindications for TPA
- Ischemic stroke or head trauma in last 3 months
- Previous ICH
- Brain cancer
- GI malignancy or hemorrhage in last 21 days
- Intracranial/spinal surgery in last 3 months
- Suspicion for SAH
- BP >185/110
- Active bleeding
- Current IE
- Suspicion of aortic arch dissection
- Platelets <100,000
- INR >1.7
- APTT >40
- Therapeutic clexane in last 24 hours
- NOAC
- Extensive hypoattenuation on CT
Timeframe for TPA in stroke
within 4.5 hours, sooner the better
Risk factors for hemorrhage post stroke
Large infarct Established infarctions Grey matter infarctions Higher NIHHS score Poor collaterals Hyperglycemia Thrombocytopenia
Dose alteplase
0.9 mg/kg - 10% as bolus and the 90% over an hour
What is the penumbra and what imaging is used to determine its size
-Tissue at risk and potentially salvagable
CBV: Shows how much is dead
Tmax: showed the penumbra
Indication for clot retrieval in stroke
CTB: does not display extensive infarct
CTA: major vessel occlusion (ICA,M1,Basilar,M2)
CTP: Large penumbra, small core
Good premorbid function
Time frame for thrombectomy in stroke
up to 24 hours, with no difference in group getting treatment closer to 24 hours
DAWN trial - NEJM 2018
Tenectaplase vs alteplase before mechanical thrombectomy
Increased rates of perfusion with tenectaplase
Alteplase vs placebo in patients with unknown time of onset of stroke
Ischemic lesion on DWI with normal flair suggesting stroke <4.5 hours
Improved perfusion with alteplase, but increased risk of death
BP control in acute stroke
Increased BP as it will improve blood flow via collaterals, may reduce extent of irreversible ischemia
Upper limit with tPA: 180/105
Non tPA may go up to 220/120
Most important modifiable risk factor for strokes
HTN
Target BP after acute setting in strokes and Tx of choice
SBP 120-140
ACEi and Thiazide have the most evidence
When to commence BP Mx drugs post stroke
48-72 hours post stroke
Antiplatelets post stroke
Short term:
-Aspirin and clopidigrel for 3 weeks, then aspirin alone (most benefit of aspirin within 6 weeks)
Long term:
- Only aspirin
- No benefit of clopidigrel over aspirin and increased risk of bleeding if both A+C used
When is the highest risk of new stroke with large vessel atherosclerosis
First month, afterwards plaque stablises
CEA vs stenting
Higher risk of peri procedural stroke and death with stenting over the age of 70s
Indication for CEA
PAtients with non disabling carotid artery territory stroke or TIA with ipsilateral carotid stenosis measured 70-99%.
Ideally within 2 weeks
Indications for stenting over CEA
Unfavorable anatomy
Symptomatic restenosis post CEA
Previous radiotherapy
Only if Age < 70
Mx of intracranial large vessel atherosclerosis
DAPT
No role for warfarin
No role for stenting
Aggressive medical Mx
Risk factors for dissection
Trauma (can be minimal) with hyperextension of the neck
Genetic predisposition
Fibromuscular dysplasia
CTDs
Clinical features of dissection
NEck pain HEadache Stroke Partial Horner's Syndrome SAH if rupture
Tx of dissection
Aspirin
Generally good prognosis with resolution of dissection in majority
When to start anticoagulation post acute stroke
0, 3, 6, 12 rule
0 days - TIA
3 days - Small stroke
6 days - medium stroke
12 days - large stroke
50% of cryptogenic strokes are due to:
PFO
Mx of PFO in stroke setting
PFO closure and antiplatelet therapy for patients <60 with no other cause of stroke found is indicated if associated with atrial septal aneurysm or moderate to large R to L shunt
Increased risk of AF in first 1-1.5 months post closure, but transient
0 % recurrence of stroke in PFO closure group
Risk of developing stroke post TIA
3.7% due to improved medical therapy
Risk stratification based on:
- Age >60
- BP >140/90
- Clinical features: unilateral weakness, speech impairment
- Duration: + points if >60 mins
- Diabetes
- Dual TIA
- Imaging: >50% stenosis of ICA, acute DWI restriction
BP management in acute ICH
Aim 140-160 (closer to 140)
Higher renal adverse events in 7 days if intensive BP control
REducing haematoma size in ICH
Evidence for lowering bp to <160 and INR <1.3 within 4 hours
Platelets in ICH
Worse outcomes. Do not use
Tranexamic acid in ICH
Fewers deaths by day 7, but same amount of deaths by 90 days
Primary causes of ICH
Deep perforating vasculopathy (atheroscleosis of small vessels)
- Basal ganglia or brainstem
- White matter lesions, lacuna strokes
Cerebral amyloid angiopathy
-Lobar inctra cerebral hemorrhage (small vessel blockage)
Causes of secondary ICH
Mets AVM aneurysm Cerebral venous sinus thrombosis IE
Cerebral Amyloid angiopathy Features
Symptomatic lobar hemorrhages
Cortical microhemorrages
White matter disease and cortical infarcts
Dementia
CAn present with TIA symptoms with positive symptoms
Cerebral Amyloid angiopathy Pathophysiology
Combo of ischemia and bleeds
Genetic association with APOE E4 and E3 allele
Amyloid deposition in capillaries, arterioles, and small arteries leads to necrosis of vessel wall and leads to rupture and small vessel occlusion
Mx of CAA
Avoid anticoagulation, antiplatelets, and thrombolysis
Mainstay BP control: Perindopril/Indapamide most evidence
Cerebral Venous thrombosis Risk factors
Hormonal therapy Post partum Thrombophilia Local infections Chronic inflammatory diseases Malignancy
Cerebral Venous thrombosis presentation
Isolated intracranial HTN (90% of cases)
SEizures
Focal neurology
Encephalopathy
Cerebral Venous thrombosis Mx
Heparin infusion or therapeutic clexane
Then transition to warfarin
3-6 month duration in provoked, 6-12 months if unprovoked
Increased risk of recurrence if occured during post partum and may require prophylactic anticoagulation in future pregnancy
Extradural haematoma on CT
Lemon
Subdural haematoma on CT
Banana
Heerfordt Syndrome
Sarcoid
Facial palsy combined with uveitis, fever, parotid enlargement, and transverse myelitis
Features of optic neuritis
Subacute onset Pain on eye movement Decreased visual acuity and colour vision Sparkles of light Relative afferent pupillary defect
(Retrobulbar - no swelling, anterior -swellin)
Leber’s Optic neuritis
Acute onset visual loss and a week later the other eye too
Mitochondrial disorder
Nil pain on eye movement
Causes of bilateral optic disc swelling
HTN
Raised ICP (papillodema)
Bilateral ON/neuropathy - NMOSD
MS HLA type
HLA DR2 (HLA DRB1*15)
Environmental factors associated with MS
EBV
Smoking
Latitude
Sunlight exposure and Vit D are protective
Pathophysiology of MS
Early axonal loss as well as demyelination
Involves cortical grey matter lesions and white matter
Both T and B cell involvement
Duration of demylinating attack in MS
LAsting greater than 24-48 hours
Nadir within 2 weeks
Resolution by 4 weeks (may not return to baseline)
Pseudo relapse can occur in setting of fevers/heat
Lhermitte’s phenomenon
an electric shock-like sensation that occurs on flexion of the neck. This sensation radiates down the spine, often into the legs, arms, and sometimes to the trunk.
Uhthoff’s phenomenon
the worsening of neurologic symptoms in multiple sclerosis (MS) and other neurological, demyelinating conditions when the body gets overheated from hot weather, exercise, fever, or saunas and hot tubs.
63% of patients with a clinically isolated syndrome will develop MS. What are the RFs to develop MS
Younger age High cerebral lesion load Asymptomatic infratentorial or spinal cord lesions GAD enhancing lesions Oligoclonal bands in CSF Abnormal visual evoked potentials
Optic neuritis and MS
20% initial presentation of MS is optic neuritis
50% of MS patients will develop optic neuritis
MS on MRI
T2 Flair is best modality Contrast enhancing of acute lesions lasts up to 1 month Typical location of lesions: -Periventricular -Juxtacortical -Infratentorial -Spinal cord
McDonalds Criteria
For Diagnosis of MS
NEED 2 LESIONS IN TIME AND SPACE
Time
- 2 seperate attacks, or even a Hx of an attack
- MRI with contrast enhancement of a lesion and no enhancement of another
- Oligoclonal bands
Space:
- 2 different locations in the CNS through objective clinical evidence
- 2 different locations in the CNS through MRI
Oligoclonal bands in CSF with CIS
High predictor of conversion to MS
Factors that are associated with an increased risk of development of primary progressive MS in radiologically isolated syndrome
Older age
Man
Spinal cord lesions
Acute treatment of MS
3 days of IV/PO MEthyprednisolone
- Accelerates rate of recovery from relapse
- No change in disability or disease
PLEX for severe disease
Interferon Beta for MS
-MOA, SE, efficacy
Modualtes T cell and B cell function, decreases expression of matrix metalloproteinases and reverses BBB disruption
Annually ~30% reduction in relapses, disability, MRI lesion activity
Reduces mortality
SE:
- Flu like symptoms
- Injection site reaction
- Depression, leukopenia, LFT derrangement, Thyroid disorders
- Some will develop Abs
Glatiramer Acetate for MS
-MOA, SE, efficacy
MOA
- Functions as an altered peptide ligand for MHC Class II
- Stimualtes TREG cells
Annually ~30% reduction in relapses, disability, MRI lesion activity
SE:
-Injection site reaction
Laquinimod for MS
-MOA, SE, efficacy
unknown MOA
-reduces leuks in CNS or modualtes cytokines
23% reduction in relapse and reduces disability and MRI lesions
SE
0Mild LFT derrangeent
Teriflunomide for MS
-MOA, SE, efficacy
From LEF
-Antimetabolite that interferes with de novo synthesis of pyramidines, blocks replication and rapidly dividing cells
31% reduction in relapse, disability progression and MRI lesions reduced by 80%
SE
-Thinning hair, GI upset, teratogenic
Dimethyl Fumerate for MS
-MOA, SE, efficacy
MOA:
- Hydrolyzed into monomethyl fumerate
- Unknown mechansm
53% reduction in relapse, 90% reduction in MRI lesions
SE:
Flushing and diarrhea
Nausea and abdo pain
PML
Fingolimod
-MOA, SE, efficacy
MOA
- Sphingosine 1 phosphate receptor modulator
- Inhibits the migration of T cells from lymphoid tissue into peripheral circulation and CNS
54% reduction in relapse and 82% reduction in MRI lesions
SE:
- First dose bradycardia
- VZV reactivation
- Macular oedema (need 3 monthly OCT)
- HTN
- LFT derrangment
- Lymphopenia
- Risk of rebound relapse after ceasing (1-2 months post) that can be more severe than prev. relapses
- PML
Cladribine for MS
-MOA, SE, efficacy
MOA
- Immunosuppresive purine antimetabolite that targets lymphocytes, folloed by reconstitution
- 2x5 da treatment one month apart then yearly
58% reduction in relase, 82% reduction in MRI lesions
SE
- HEadaches
- Lymphopenia
- Herpes Zoster
- Malignancy (increased risk with treatment >2 years)
Natalizumab for MS
-MOA, SE, efficacy
MOA
- targets a4b1 integrin
- Inhibits the leucocyte migration across the BBB by blocking the interaction between a4 integrin on leuks and the vascular cell adhesion molecule 1 on endothelial cells
68% reduction in relapse, 92% reduction in MRI lesions
SE:
- Anxiety, pharyngitis, peripheral oedema, infusion related symptoms
- 6% develop persistant anti natalizumab ab
- PML
- Risk of rebound relapse with cessation
PML features
Subacute worsening visual, motor, or cognitive change with gradually enlarging T2 hyperintensities with minimal or no gad enhancement
Mx of PML
PLEX
CAn trial Pembrolizumab
Can develop IRIS post PLEX abou 2-5 weeks post PLEX
Alemtuzumab for MS
-MOA, SE, efficacy
MOA
- Targets CD52 (T and B cells) and leads to lyphopenia
- yearly infusion for 2 years
SE:
- Infusion reaction
- ITP
- Graves disease
- Anti GBM
- Increased infection risk, herpes
Ocrelizumab for MS
-MOA, SE, efficacy
MOA
- Targets CD20
- Similar mechanism to rituximab
Effective in Primary Progressive MS (need Hx of OGB in CSF previously)
Slows the disability, doesn’t cure it.
Siponimod for MS
-MOA, SE, efficacy
MOA
- Selective Sphingosine 1 phosphate receptor 1 and 5 modulator
- 2nd gen Fingolimod
- may prevent neurdegeneratio nand promote remyelination
Indication: Secondary progressive MS
SE: -First dose bradycardia -VZV dissemination -Macualr oedema HTN -LFT derrangement Lypmhopenia
Mitoxantrone for MS
-MOA, SE, efficacy
MOA
-Chemo agent: inhibition of B cell, T cell, and macropage proliferation
For aggressive RRMS, secondary progressive MS
SE: Cardiac toxicity (CI if EF <50%) or drop during treatment
MS and pregnancy
MS relapses are reduced in pregnancy, but not completely.
Increased risk of relapse post partum
Tx of MS in pregnancy
CAn use: IFB Glateramer Acetate Alemtuxumab Rituximab/Ocrelizumab - avoid in 2nd/3rd trimester
Features of NMO
Relapsing B cell mediated disease targeted agaisnt astrocytes
-More severe than MS with likely permanent residual damage
PRsentation
- Optic neuritis
- Acute myelitis (contiguous spinal cord MRI lesion over 3 vertebral segments)
- Area postrema syndrome (episodes of otherwise unexplained hiccups or nausea and vomiting)
Anti AQP4
NMO
MOG Ab
NMO, ADEM
-Steroid responsive
Tx of NMO
Acute: IV Methylpred or PLEX
Chronic:
- Eculizumab, Ritux, AZA, MTX
- Inebilizumab (CD19 depletion)
- Satralizumab (Anti IL 6 receptor)
ADEM
USually preceeded by viral infection
Resolves after 3 months
Neurological symptoms assocaited with encephalopathy
SOD1 mutation
Gain of function mutation for motor neuron disease
C9orf72
Motor neuron disease
TDP-43 cytoplasmic inclusions
Dementia in ALS - Tau process
ALS patients get frontotemporal dementia - executive function and verbal fluency loss
Ocassional overlap with PSP/PArkinsons
NCS in Motor neuron disease
Decreased CMAP
Normal SNAP
Tx of MND
Riluzole - inhibitor of glutamate relase
-Extends survival by 3-6 months
Edaravone
- Potential free radical scavenger to reduce oxidative stress
- Mild reduction in progression (only safe to use up to 6 months)
What is a motor unit
a single motor nerve and all of the muscle fibres it innervates
Fibrillation potentials and positive sharp waves on EMG
Spontaneous firing of individual muscle fibres
Sign of ACTIVE DEMYELINATION
Can occur in inflammatory myopathies
Faciculations on EMG
Firing of all parts of the motor unit
- MND
- CIDP
- Chronic nerve entrapment
- Cal also occur in benign fasciculation syndrome
EMG - Neurogenic changes
Spontaneous: Faciculations
Morphology: Large amplitude , widened duration
Recruitment: Decrased
EMG - Myogenic changes
Morphology: small amplitude
Recruitment: Increased
MG Antibodies
AChR (85%) - Correlates with thymoma or thymic hyperplasia
MuSK (6-10%)
Features of MG with MuSK ab
Non-white, young female
Early onset
Not related to thymoma
Generalised MG
Severe disease with resp and bulbar involvement
Poor response to treatment, good response to rituximab
How does Tensilon Test work
Administration of edrophonium (short acting acetylcholinesterase inhibitor)
Given with atropine at bedside
Diagnostic findings on Repetitive nerve stimulation for MG
10% decline in amplitude with repitation
-Good for generalised MG
Single fibre EMG best for ocular MG
Mx of MG
- Pyridostigmine (Cholinesterase inhibitor)
- Steroids - reduce risk of developing generalised MG - can worsen before improving usually after 4-5 days of starting
- AZA/MMF/Tac/RTX/IVIG/PLEX
- Eculizumab in severe cases
Thymoma removal if present
MG Crisis: IVIG, PLEX, Steroids, Supportive care and intubation
Meds that can cause G crisis
BB CCB (verapamil) Aminoglycosides Fluroquinolones Tetracyclines Macrolides Phenytoin Lithium
MG and pregnancy
Exacerbation in 1st trimester and post partum
Settled during 2nd and 3rd trimester
LEMS Clinical features
Prosimal weakness - improved post exercise
Autonomic features - Dry mouth, erectile dysfunction, constipation, urinary issues, orthostatic hypotension
Areflexia
VGCC antibodies
LEMS
Tx of LEMS
Tumor resection (SCLC usually paraneoplastic)
3-4 diaminopyridine - Blocks efflux of K+ ions prolonging duration of depolarisation
IVIG
PRed
MOA of Botulism
Anaerobic spore forming Gram positive bacillus
Inhibition of presynaptic acytelcholine release
Features of Botulism
Incubation 2 days N+V Symmetric descending flaccid paralysis Autonomic involvement - Dry eyes, mouth, paralytic ileus, urinary retention Mentation and reflexes preserved
Mx of botulism
Equine antitoxin
- Avoid aminoglycosides
- REmove toxin if ileus and not absorbed
Recovery over months
Anti synthetase syndrome
ILD FEver Polyarthritis MEchanic hands Raynauds
Anti Jo1 ab
Anti cN1A
Inclusion body myositis
Anti SRP
Necrotising autoimmune myositis
Types of generalised seizures
Tonic clonic
Absence
Myoclonic
Atonic
Juvenile absence epilepsy features and Mx
Absece seizures and occasional GTCS
Generally cease in late teens
Mx - Valproate
JME features and Mx
ICK Gene in 7 % (Intestinal cell kinase)
Myoclonus in nearly waking states
CAn have GTCS and absence seizures
Wose with sleep deprivation and ETOH
Mx
- Valproate
- Lamotrigine - women of child bearign age
- Zonisamide
Prognosis - poor remission
3 Hz spike/polyspike wave discharges
Buzzword for JME
Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis
Most common form of epilepsy
Risk factors: Prolonged febrile convulsions, CNS infections
Typical auras, focal seizures with impaired awareness with or without automatisms
-Deja vu, gustatory/olfactory hallucinations, epigastric rising sensation
Usually medically refractory and requiring surgery
EEG: Alpha 9-12 Hz
Normal Wakefullness
EEG: Beta 13-15 Hx
Too much Benzos
EEG: Theta 5-8 Hz
Drowsy or encephalopathic
EEG: Delta 1-4 Hz
Sleep or encephalopathic
EEG: Spike and wave
Epileptogenic
When to treat seizures
After 2 seizures no more than 1-2 years a part
EArly treatment if high risk of recurrence or in vulnerable population
Tx of choice for focal seizures
- Carbamazepine
- Lamotrigine
- Gabapentin
- Keppra
- Valproate
- Phenytoin
Tx if choice for absence seizures
- Valproate
2. Ethosuzimide
Tx of choice for Generalised epilepy
- Valproate
- Lamotrigine for women of child bearing age
- Zonisamide
Carbamazepine and SJS HLA type
HLA B*1502 - Han Chinese, thai, malay, filopino
HLA A *3103 - Europeans
Best known combo for dual therapy in epilepsy
lamotrigine and valproate
Role of hormones in epilepsy
Estrogen promotes neuroexcitatory properties
Progresterone promotes neuroinhibitory properties
Lamotrigine levels lowered by OCP
OTher AEDs induce rapid clearance of OCP
Best tolerated AEds in pregnancy
Lamotrigine and carbamazepine
Note that lamotrigine and keppra undergo increased clearance and will need increased dose at some point in pregnancy
Risk factors for SUDEP
GTCS > 2 years
Nocturnal seizures
Treatment resistant seizures
Long duration of epilepsy and early stage of onset
Dravet Syndrome - Na channel gene mutation
Mx of Status epilepticus
- Benzos - IV Loraze 2-4 mg; Midaze 10 mg IM
- Load with AED - Rule of thumb 20 mg/kg
- Midaze/propofol infusion
- Pentobarbitol
Monitor BSL as will drop with prolonged status
MOA Carbamazepine and SE
Sodium channel
SE: -Diplopia/dizziness/drowsiness -SJS/Rash -Aplastic anaemia Hyponatremia -Hepatotoxicity -Lupus like syndrome -WEight gain -Decreased bone mineral density
MOA and SE Keppra
Inhibits presynaptic calcium channels reducing neurotransmitter release and acting as a neuromodulator
SE:
- Psychosis/irritability/hostility/depression
- Dizziness
MOA and SE Phenytoin
Sodium channel
SE:
- CAn worsen absence and myoclonic seizures
- Ataxia, nystagmus, diplopia
- Blood dyscrasia
- Behavior changes
- Skin thickening/gingival hyperplasia/hirsutism/corsening facial features/Acne
- Peripheral neuropathy
- Bone disease
MOA and SE Valproate
PIP3 reduction, sodium channel, Increases GABA
SE:
- WEight Gan/PCOS like syndrome/ menstrual cycle issues
- Thrombocytopenia
- Teratogenic ++
- Acute liver failure/pancreatitis
- Alopecia
- PArkinsons/dementia
CGRP
Calcitonin Gene Related Peptide
- Produced by trigeminal ganglion and released in nerve endings
- Most potent dilator of cerebral and diral blood vessels
- Release of inflammatory mediators from mast cells
- Increased levels during a MIGRAINE
Hemiplegic migraine
weakness tkes up to 72 hours to reseolve
Need to rule out stroke or TIA
FMH1 mutation of CANCNL1A4 gene (coding for calcium channel)
Migraine prophylaxis medication options
Amitryptylline Propanolol Topiramate Candesartan Pizotifen
New role for CGRP inhibitors
Cluster headaches
Male predominence
Occur nearly daily lasting 15-180 mins
Follow circadian cycle - predominantly nocturnal
Sharp stabbing pain with ipsilateral autonomic features
Restlessness and agitation
Acute Tx - Triptans, High flow O2 with non rebreather
Bridging Tx - steroids, occipital nerve block
Prevention - Verapamil SR TDS
Paroxsymal Hemicrania
Similar to cluster but..
Female predominant
5-10 times per day lasting 2-20 mins
Complete an absolute response to indomethocin (diagnostic)
Melatonin trial if indomethocin responsive
Hemicrania continua
Constant unilateral, side locked headache
assoacited with autonomic features and restlessness
Daily to near daily lasting 30 mins to 3 days
Tx: indomethicin responsive
SUNCT/SUNA
Short lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing
Stabbing lancinating burning pain, orbital pain
Up to 100 times per day lasting 1-600 seconds
Tx: Lamotrigine
O2 and indomethocin do nothing for this
Trigeminal neuralgia
20 x increase risk in MS - esp. bilateral TN
V2 distribution most common
Usually due to neurovascular compression
Tx: CArbamazepine, microvascular decompression
Idiopathic intracranial HTN RF and secondary causes
Unknown cause
RF: Female, obese, reproductive age
SEcondary causes: Venous sinus thrombosis Tetracycliens, fluroquinolones Vit A - tretinoin Iron deficiency OSA Raised CSF protein
Diagnsotic criteria for IIH
Papillodema
Normal neuro exam except CN abnormalities
Normal MRI and CSF
CSF opening pressure > 25 mmHg
IIH management
WEight loss Acetazolamide Topiramate VP shunt Optic nerve seath fenestration Venous stenting
Aceazolamide MOA
Potent ezyme inhibitor of carbonic anhydrase, and it impedes the activity at the choroid plexus reducing CSF secretion
Intracranial hypotension
Postural headache worse on standing or sitting and better when laying flat
Most common is post LP headache
Mx:
bed rest, fluids, coffee, epidural blood patch, surgical repair
Eseential tremor
Bilateral, slow progression
ETOH may help, but not diagnostic
Mx: Propanolol, DBS, USS Thalamotomy, Primidone
Intention tremor
Worse on end of movement and suggests cerebellar involvement
Holmes tremor
Unilateal, rest, postural, movement, and worse on intention
Seen in wilson’s disease, stroke, MS
Dystonia
Sustained r intermittant muscle contractions causing abnormal often repetitive movements, postures, or both
Movments are typically twisting
Initiated or worsened by voluntary action
Mx: Botox
Chorea
Involuntary movmeent of limbs, trunk, neck, or face wjich rapidly flit from region to region in an irregular pattern
Dyskinesia
Chorea movement with parkinsons
FEatures of presymptomatic stage of PArkinsons
Anosmia
Constipation
REM sleep disorder
Mood changes, increasing fatigue
Inclusion criteria for PArkinsons
Decrementing bradykinesia
Rigiditiy
4-6 Hx rest tremor
Side effects of L Dopa
Sedation, N+V Dyskinesia, mtor fluctuations Impulse control disorders (in high doses) Punding Dopamine dysregulation - abuse
Motor complications in PArkinsons
On - Well
Off - Full blown parkinsons
Dyskinesias - too much drugs
Will have mtr fluctuations and dyskinesias after 5 years of treatment
Risk factors for motor fluctuations in PD
Longer disease duration
Higher levels of L Dopa used
Younger onset of PArkinsons
Mx of motor fluctiations in PD
Divide dose into increased freq.
Add on COMT or MAO
Dyskinesia treatment in PD
minimise dopaminergic meds
Amantadine
Break up doses into higher frequency
Amantadine MOA
Weak antagnist of the NMDA type glutamate receptor, Increases dopamine release and blocks dopamine reuptake
DA agonist - names, MOA
MOA: Stimulate dopamine by binding directly to post synaptic dopamine receptors in the striatum
MEds:
-Non Ergot DAs: Pramiprexole, Ropinirole, Transdermal rotigotine, Apomorphine
-Ergot derived: CAbergoline, bromocriptine, pergolide
SE of CAbergoline, bromocriptine, pergolide
Heart valve complications and retroperitoneal fibrosis
SE DA agonists
Nausea, somnolence, oedema, dizziness, hallucinations, hypotension
Worsens delirium
Impulse control disorders
MAO B inhibitors names and SE
Rasagline, selagiline
USed in early/young patients
SE: LFT derrangement INSOMNIA - most common Higher overall mortality Tyrasine hypertensive crisis -Tyrasine releases NA and ordinarily MAO A breaks down excess, if MAOI then adrenergic crisis
Exenatide in Parkinsons
GLP1 receptor agonst
Improves medication motor scores
Likely symptomatic improvement rather than neuroprotective
Order of ceasing PD meds in setting of delirium and hallucinations
- Anticholinergic meds
- Amantadine
- DA
- MAOI
- L Dopa
Why can meds not be stopped abruptly in PD
PArkonsonian crisis - NMS
Strongest predictor of dementia in PD
Age not duration
Alpha synneuclianopathies
PD
DLB
MSA
Tau protein opathies
PSP
Corticobasalar degeneration
PSP Triad and MRI findings
Supranuclear palsy, postural instability, dementia
- Early falls
- Psuedobulabar palsy: dysarthria anddysphasia
Hummingbird sign on MRI (midbrain atrophy)
MSA FEatures and MRI findings
Autonomic failure, Parkinsonism, Cerebellar signs
Hot cross bun sign
Corticobasal syndrome
Cortical dysfunction and basal ganaglia dysfunction
Asymetric progressive ideomotor aprazia that frequently affects the hand and is associated with rigidity myoclonus and dystonia
Alien hand
FMR protein deficiency
FXTAS/Fragile X syndrome
HTT Protein
Huntingtons
-CAG repeat, paternal anticipation
HTT protein is toxic to striatal neurons
Spinocerebellar ataxia
CAG repeat disorder
CAn be AD, AR, X linked
Variable syndromes, but predominantly ataxia and UMN signs
Differentiating Serotonin syndrome from NMS
SS:
- Acute onset <24 hours
- Myoclonus, Hyperreflexia, rigidity
NMS
- Slower onset
- CK rise and rigidity
HSV encephalitis
Herpes PCR can be negative in first 24-48 hours and should recheck if high suspicion
MRI: Y2 hyperintensity in medial and inferior temporal lobe extending up insular cortex
EEG: focal slowing
Tx: IV Aciclovir 14-21 days
Listeria encephalitis
Most commonly rhomboencephalitis - brainstem involvement
Incidence higher in pregnancy, elderly, immunosuppressed
Tx: Benpen, ampicillin
Anti Hu
Limbic encephalitis, peripheral neuropathy
SCLC
Anti Yo
Cerebellar degeneration
Breast/Ovarian cancer
Anti Ri
Opsoclonus myoclonus, rhomboencephalitis
SCLC
Anti Ma/Ta
Rhomboencephalitis - NArcolepsy, Vertical gaze disorder
Testicular cancer
NMDA encephalitis
F>M
50% of young women have ovarian teratoma
Most common cause of AI encephalitis
PResent with preceeding viral prodrome and then associated with psychosis, hallucinations, behavioral changes
NMDA antibodies oresent
MRI: Temporal lobe limbic changes
Tx of NMDA encephalitis
Remove cancer IV methylpred, then PO pred IVIG or PLEX Rituximab Cyclophophamide
LGI1 antibody
Voltage gate potassium channel encephalitis
Cognitive and memory changes
Faciobracial dystonic seizures
CASPR2 ab
Voltage gate potassium channel encephalitis
VGKC Ab
Voltage gate potassium channel encephalitis
PRES RFs
Clincial and radiological syndrome of encephalopathy and posterior circulation oedema
RFs: HTN Pre-eclampsia REnal failure Autoimmune conditions
PRES Tx
Aggressive BP control
Seizure Mx
Effect on NCS in radiculopathy and pre ganglionic lesions
Normal NCS
What does a low amplitude on NCS represent
Axonal loss
What does increased latency or decreased conduction velocity on NCS represent
Demyelination
NCS in Compression lesions
Focal demyelination - drop in velocity at lesion site
Oeer time will get drop in amplitude, then change in motor conduction
What is SNAP for NCS
Sensory nerve action potentials - the sum of the resultant APs
What is CMAP for NCS
Compound muscle action potential - sum of all the APs in the muscle fibre
Conduction Block on NCS
Specific point that the nerve has slowed conduction
Drop in CMAP amplitude between proximal and distal sites of the same nerve
F wave on NCS
Only way of looking at proximal segment of nerve
May be only abnormality in early GBS
Delayed F wave if dysfunction
Risk factors for carpel tunnel
Female Diabetes PRegnancy RA Hypothyroidism HAemodialysis Steroid use
Mononeuritis multiplex presentation
painful neuropathy which is not at a place of compression
Due to inflammation of blood vessel within the nerve - both small and large fibres are affected - motor and sensory
Definitive testing is biopsy
3rd nerve palsy determining compression vs vascultitis
Compression - dilates first
Vasculitis - Motor, then pupil dilates later or can be pupil sparing altogether
Sarcoid induced neuropathies
Polyradiculopathy
Peripheral neuropathy
Mononeuropathy multiplex
Bilateral CN7 palsies - Always consider sarcoid
Hereditary neuropathy with liability to pressure palsy
HNPP
PMP22 gene reciprocal deletion
AD
Characterised by transient and recurrent motor and sensory mononeuropathies, typically occuring at entrapment sites
Peripheral neuropathy always affects feet before hands. If it is the other way around who do you need to consider as the cause
Dorsal root ganglion or cervical injury
DDX for autonomic failure
Diabetes
MSA
Amyloid
Paraproteinemic Peripheral neurpathy causes
- MGUS - If present not always cause - IgM most common
- Waldenstroms - distal acquired demyelinating symmetric neuropathy
- MM
- POEMS
- Amyloidosis - Painful length dependent PN with generalised autonomic failure
Chemo agents that cause PN
Platinum based chemo
Taxanes
Vinca ankaloids
Bortezomib
Neuropathies in B12 deficiency
PN
Corticospinal tract
Dorsal column
RAdiculopathy features
Asymmetric
Follow a dermatome or myotome
PAINFUL
Can be sensory or motor
Zoster sine herpete
Neuralgiform pain with no rash
Miller Fisher Syndrome
Type Of GBS
Opthalmoplegia, areflexia, ataxia
Anti GQ1b
Miller Fisher Syndrome
GBS presentation
Prodrome in the 4 weeks prior to onset of symptoms
Symmetric ascending weakness
CAn be associated with radicular pain
Proximal and distal weakness is usually the predominant feature
Hyporeflexia or areflexia can be delayed by 1 week
WEakness nadir by 2-4 weeks
–If progressive Sx post 4 weeks then rethink Diagnosis ?CDIP
NCS in GBS
Prolonged F wave latency
Prolonged distal latencies (demyelinating) - motor before sensory
Sural nerve is often preserved
Anti GD1a and GM1
Acute motor axonal neuropathy/Multifocal motor neuropathy with conduction block
(GBS varient)
Tx of GBS
- PLEX - Reduces time to walk unaided and time on ventilator - USe within 2-4 week onset
- IVIG -use within 2 weeks onset for most benefit in those unable to walk unaided
NO STEROIDS - worse outcomes
Poor prognostic markers in GBS
Rapid onset prior to presentation High diability nadir Severely reduced CMP Older than 40 yo PReceeding diarrheal illness, C. Jejuni PReceeding CMV infection Inexcitable nerves
CIDP
Chronic inflammatory demylinating polyradiculopathy
Chronic version of AIDP
Nadir > 4 weeks
Usually milder phenotype and rarely has resp involvement
Similar NCS findings to AIDP
Tx
-Steroids, steroid sparing agents, IVIG, PLEX
NF155
Contactin 1 Ab
Severe CIDP
Mx: Rituximab
Multifocal Motor neuropathy with conduction block
Immune mediated condition with asymmetric peripharl motor loss
Usually upper extremeties
Atrophy and EMG evidence of axon loss over time
Deep tendon reflexes usually decreased
Anti GM1 in 40-80%
IVIG and steroids can worsen the condition
Dorsal root Gangiolopathy
Pure sensory loss
UL before LL or same time as LL
Causes: Sjogrens, Anti Hu, B6 deficiency
Parsonage-Turner Syndrome
Neuralgic amyotrophy, brachial neuritisL Pain and muscle atrophy
-Severe shoulder and arm pain followed by weakness and numbness
Usually middle aged men, but can be anyone
Tx: steroids and analgesics
Diabetic Amyotrophy (Lumbosacral Radiculoplexopathy)
Age >50 and men usually
SEvere unilateral pain in the back, hip, or thigh that spreads to involve the entire limb and can involve the other leg within weeks or months
-Proximal weakness shortly after the onset of pain, and then can become widespread
Not related to glucose control or duration of diabetes
LEvel above which consciousness is associated
medulla
Topiramate MOA and SE
stabilises presynaptic neuronal membranes by blocking voltage-dependent sodium channels. Enhances activity of GABA on postsynaptic chloride channels.
SE:
-Psych stuff
Renal stones
by rapidly progressive dementia, myoclonus and periodic tri-phasic sharp waves on EEG?
JC Virus
Stroke Syndrome:
MCA inferior devision
Contralateral visual loss - homonymous hemianopia Contralateral visual loss - upper quadrant anopia
Contralateral constructional apraxia (non-dominant hemisphere)
Contralateral aphasia - receptive (dominant hemisphere - Wernicke’s area)
Stroke Syndrome:
MCA superior devision
Contralateral weakness - upper and lower limb (Face, arm>leg) Contralateral weakness - face - lower half Contralateral hemisensory loss - upper and lower limb Contralateral sensory loss - face - all modalities Contralateral hemineglect (non-dominant hemisphere) Contralateral aphasia - expressive (dominant hemisphere - Broca’s area)
Balint Syndrome
If affecting bilateral posterior cerebral arteries
Affects bilateral parietal-occipital lobes
Bilateral loss of voluntary but not reflex eye movements
Bilateral optic ataxia - poor visual-motor coordination
Bilateral asimultagnosia - inability to understand visual objects
Claude syndrome
Ipsilateral eye movement weakness (oculomotor palsy)
Contralateral ataxia - arm and leg (cerebellar tracts)
Contralateral tremor
Posterior cerebral artery - Unilateral occipital
Contralateral visual loss - homonymous hemianopia (optic pathway, calcarine cortex)
Thalamic Pain syndrome
Dejerine-Roussy Syndrome
Penetrating branches to thalamus
Contralateral hemisensory loss - all modalities
Contralateral hemi-body pain
Weber Syndrome
Penetrating arteries to midbrain
Contralateral weakness - upper and lower limb (corticospinal tract) Ipsilateral lateral gaze weakness (CnIII)
Lateral pontine syndrome
Marie-Foix syndrome
AICA
Ipsilateral ataxia - arm and leg (cerebellar tracts) Contralateral weakness - upper and lower limbs (corticospinal tracts) Contralateral pain and temperature loss (spinothalamic tracts)
Lateral medullary syndrome
Wallenberg syndrome
PICA
Small penetrating arteries
Ipsilateral loss of pain and temperature from face + facial pain (Cn5 nucleus)
Ipsilateral ataxia - arm and leg, gait ataxia (Restiform body, cerebellum)
Ipsilateral nystagmus, N&V, vertigo (Vestibular nucleus)
Ipsilateral hoarseness and dysphagia (nucleus ambiguus)
Ipsilateral Horner’s syndrome (descending sympathetics)
Contralateral loss of pain and temperature from body (Spinothalamic tract)
Hiccoughs
Medial medullary syndrome
Dejerine syndrome
Vertebral ARtery/anterior spinal
Contralateral weakness of upper and lower extremity (Pyramidal tract) Contralateral hemisensory loss - vibration and proprioception (Medial lemniscus) Ipsilateral tongue weakness +/- atrophy (Cn12 nucleus)
Inferior medial pontine syndrome
Foville syndrome
Basilar artery
Unilateral lesion affecting the dorsal pontine tegmentum in caudal third of pons
Contralateral weakness - upper and lower limbs (corticospinal tract)
Ipsilateral weakness - face - entire side (CnVII nucleus/fascicle) Ipsilateral lateral gaze weakness (PPRF or CnVI nucleus)
Locked-in syndrome
Basilar artery
Affects bilateral ventral pons Bilateral weakness - upper and lower limb (Bilateral cortical spinal tracts) - quadriplegia Bilateral weakness - face - entire side (bilateral corticobulbar tracts) Bilateral lateral gaze weakness (bilateral fascicles of CnVI)
Dysarthria (bilateral corticobulbar tracts)
Ventral pontine syndrome
Raymond syndrome
Basilar artery
Affects ventral medial pons
Ipsilateral lateral gaze weakness (CnVI) Contralateral weakness - upper and lower limb (pyramidal tract)
Ventral pontine syndrome
Millard-Gubler syndrome
Basilar artery
Affects basis pontis and fascicles of CN VI and VII Contralateral weakness - upper and lower limb (pyramidal tract) Ipsilateral lateral gaze weakness (CnVI) Ipsilateral facial weakness (whole side) (CnVII)
