Neurology Flashcards
What does this scan show?
Anterior cerebral artery aneurysm bleed
Circle of Willis
What are the side effects of ocrelizumab?
Anti CD20 for MS
- infusion reactions
-respiratory tract infections - malignancy including breast Ca
- hepatitis B reactivation
What are side effects of dopamine agonists in PD?
Dopamine agonists generally preferred in younger patients; avoid in older due to ADRs
examples - pramipexole, ropinirole, rotigotine, cabergoline
ADRs
- nausea, vomiting
- drowsiness
- hallucinations, confusion
- orthostatic hypotension
- impulse control disorders
- can get dyskinesias but less common than levodopa
- abrupt cessation leads to dopamine agonist withdrawal syndrome (anxiety, panic attacks, dysphoria, depression, dizziness / orthostatic hypotension)
What are the clinical features of GBS?
Typical features of AIDP (most common variant of GBS)
- acute onset, symmetrically, bilateral rapidly progressive ascending flaccid weakness
- reduced or absent tendon reflexes
- sensory symptoms - paraesthesia, radicular back pain
- dysautonomia (70%) - cardiac arrhythmia, labile BP, excessive sweating, ileus
- respiratory muscle weakness -> can progress to respiratory failure (10-30%)
- monophasic illness pattern
- interval between onset of illness and nadir of weakness is between 12 hours - 28 days
Symptoms atypical for GBS
- weakness progresses to nadir <24 hours or > 4 weeks
- sensory level
- asymmetric weakness
- bowel & bladder dysfunction at onset
- pulmonary dysfunction with little or no limb weakness at onset
- isolated sensory signs with no weakness at onset
- fever at onset
What are the indications for intubation in GBS?
FVC < 20 mL/kg or 60% predicted
Maximum inspiratory pressure < 30 cm H20
Maximum expiratory pressure < 40 cm H20
Why is carbidopa co-administered with levodopa?
Carbidopa is a peripheral carboxylase inhibitor
This prevents peripheral conversion of levodopa to dopamine
This prevents side effects including nausea, vomiting, orthostatic hypotension
Peripheral dopamine does not cross BBB
By preventing peripheral conversion with peripheral decarboxylase inhibitor, smaller doses of levodopa are required to achieve intended therapeutic effects centrally
In patients with significant nausea, may need supplemental doses of carbidopa
What does this scan show?
Non-contrast CTB showing an acute L) sided basal ganglia haemorrhage (most likely due to hypertension) with intraventricular extension with partial effacement of left lateral ventricle with no significant hydrocephalus or midline shift
At what level does the spinal cord end? Where should a LP be performed?
Spinal cord ends at L1
Conus terminalis is at L1/2
LP should be at L3/4 or L4/5
Absolute & relative contraindications to thrombolysis
Absolute contraindications
- extensive hypoattenuation on CT
- intracranial neoplasms
- current or prior intracranial bleed or suspicion for SAH
- severe head trauma in last 3 months
- intracranial or intraspinal surgery
- platelets <100
- INR > 1.7
- APTT >40
- clexane in last 24 hours
- suspicion for current endocarditis
- active GI or internal bleed
- aortic arch dissection
Relative contraindications
- mild & non-disabling symptoms
- stroke in last 3 months
- post-partum period
- arterial puncture of non-compressible site
- anterior STEMI in last 3 months
- major trauma in last 14 days
- major surgery in last 13 days
- NOAC
- bleeding diathesis (renal failure, liver failure, haem issues)
- large or giant aneurysm or other intracranial vascular malformation
What does this MRI show?
Right optic nerve shows enhancement on post contrast T1 weighted image suggestive of optic neuritis
What is the utility of diffusion weighted and FLAIR (fluid attenuated inversion recovery) MRI in acute stroke?
Infarct that is seen on DWI but NOT on FLAIR is likely to be within the 4.5 hour time window for thrombolysis
DWI-FLAIR mismatch on MRI can be used to select patients for thrombolysis when timing of symptom onset is unknown
Lancet 2011 trial - less intracranial haemorrhage and better functional outcome at 90 days with use of DWI-FLAIR to identify patients for thrombolysis
What are the features of conus medullaris syndrome?
- at L1- L2 level
- acute, bilateral onset
- less marked motor weakness (UMN); symmetrical
- early & severe sphincter dysfunction
- saddle anaesthesia with dissociative sensory loss
- less severe pain; symmetrical
Causes - disc herniation, trauma, tumours
What is the interaction between sodium valproate & lamotrigine?
What are the symptoms of lamotrigine toxicity?
Concurrent use of sodium valproate & lamotrigine can increase the risk of lamotrigine toxicity
This is because they are both metabolised in the liver by cytochrome p450 enzymes (CYP3A4 and CYP2C19). Sodium valproate can inhibit these enzymes leading to build up of lamotrigine
Symptoms of lamotrigine - nausea, dizziness, vomiting, ataxia, blurred vision
In severe cases lamotrigine toxicity can lead to seizure, coma, death
What are the clinical features of Meniere’s disease?
- clinical diagnosis
- triad: episodic intense vertigo, unilateral tinnitus and sensorineural hearing loss
- aural fullness & nausea are associated symptoms
- features of hearing loss - high tone hearing loss with recruitment but no tone delay
Genetics of Huntington’s disease
Autosomal dominant disorder caused by expansion of cytosine adenine guanine (CAG) trinucleotide in the HTT gene on chromosome 4 that encodes the huntingtin protein, resulting in an expanded polyglutamine tract
Atrophy of the caudate & putamen (neostriatum within the basal ganglia)
Main determinant of age of onset is the number of CAG repeats in the HTT gene
more repeats => earlier onset
<28 = normal
28-35 - will not develop symptoms but next generation is at small risk to develop expansion
36-39 - incomplete penetrance, individuals may develop symptoms but typically at a late age of onset
> 40 repeats = full penetrance
Diagnosis under <20 yrs = juvenile HD or the Westphal variant (<10% total cases)
What is the underlying pathophysiology in Parkinson’s disease?
-> Alpha synucleinopathy
- Alpha synuclein = misfolded protein that accumulates in Lewy bodies & Lewy nitrites
Lewy body = eosinophilic intracytoplasmic inclusions with a faint halo consisting of alpha synuclein, ubiquitin & other proteins
Lewy nitrites = intra-axonal inclusions
Rupture of lysosomes by alpha -synuclein aggregates
Oxidative stress
Leading to nerve cell death
Pathological process progresses from medulla (dorsal motor nuclei) & olfactory bulb towards substantial nigra -> cortex
Loss of pigmented cells in substantia nigra leads to motor symptoms
Risk factors for Parkinson’s disease
- Male predominance
- Age
- approx. 80% > 65 yrs.
Younger onset -> slow progression & longer absolute survival
Older onset -> rapid progression & cognitive decline - Genetics
- Glucocerebrosidase (GBA) mutations - 10% (variable penetrance)
- LRRK2 mutations - 1-2% (variable penetrance)
Monogenetic PD (e.g. Parkin ; PKRN) have no Lewy bodies - Heavy metal exposure
- Pesticide exposure
- Caffeine & smoking are protective
What are the early / prodromal features of PD?
Early features that can predate motor manifestations by several years
- Rapid eye movement (REM) sleep behaviour disorder
- dream enhancement behaviours (e.g. vocalising, kicking, punching) due to loss of normal atonia (muscle paralysis) of REM sleep
RBD in PD is associated with more rapid cognitive impairment, more psychiatric comorbidities, poorer treatment response, more widespread brain atrophy
RBD correlates with freezing of gait
- Constipation
- Hyposmia / olfactory dysfunction
Motor features of PD
Non-motor features of PD
What is the underlying pathogenesis of the lesion in this CT brain?
Non-traumatic lobar haemorrhage in older adults is most commonly due to amyloid angiopathy
- incidence of CAA is strongly age dependent
- amyloid beta peptide deposits in small-medium blood. vesse;s of older patients (>50 yrs.) and causes vascular fragility
- often recurrent or multifocal (unlike hypertensive haemorrhage)
- APOE e4 allele is associated with increased risk of deposition of amyloid beta-peptide
Other imaging features cerebral amyloid angiopathy
- lobar haemorrhage
- cortical superifical siderosis / haemorrhage
- microhaemorrhage
- microinfarcts
- convexity SAH
- leukoaraiosis (white matter disease along ventricles)
What are the findings of MSA on MRIB?
Atrophy of the middle cerebellar peduncles, pons, putamen & cerebellum
Increased diffusivity in the putamen
Hypointensity of the putamen relative to globus pallidus
Hot cross bun sign in the pons - due to selective degeneration of transverse pontocerebellar tracts and median pontine raphe nuclei
**MRI in Parkinson’s disease is normal
What are the complications of abrupt cessation of dopamine replacement / levodopa?
- Acute akinesia
- sudden deterioration in motor function that persists > 48 hours
- life threatening
- transiently unresponsive to PD medications - NMS
Describe the findings in a L) sided MLF lesion
L) sided MLF lesion will produce a L) sided INO
L) MLF stimulates the L) oculomotor (CN III nucleus) which innervates the medial rectus => therefore the L) eye (ipsilateral) will be unable to adduct
R) eye (contralateral eye) will have nystagmus on abduction
Features of Parkinson disease dementia
Diagnostic criteria for Parkinson’s disease
Decrementing bradykinesia PLUS rigidity and/or resting tremor (4-6 Hz)
What is the role of COMT inhibitors?
Inhibits catechol-O-methyl transferse which converts levodopa into 3-OMD. Prolongs & potentiates the effect of levodopa.
No role for combining COMT with levodopa as part of initial therapy for PD
In patients with motor fluctuations, addition of COMT inhibitors reduces “off” time
Dose reduce levodopa when COMT inhibitor added to avoid exacerbating dyskinesia
Examples of COMT inhibitors - entacapone, opicapone, tolcapone.
Entacapone and opicapone are considered safer. Tolcapone is associated with transaminitis & rare cases of fulminant hepatotoxicity
What are predictors of rapid progression in Parkinson’s disease? What are predictors of flow progression in Parkinson’s disease?
Predictors of slow progression
- young age at onset
- female sex
- tremor predominant
Features of rapid progression
- older age
- male sex
- gait & balance issues predominant
- bradykinesia as initial symptom
- dementia
- poor response to levodopa
Treatment for REM sleep behaviour disorder in Parkinson’s disease
Low dose clonazepam at bedtime
Melatonin
Mirtazepine, tramadol & beta blockers may make it worse
What are the side effects of COMT inhibitors?
Primarily due to increased dopaminergic stimulation - dyskinesia, psychiatric side effects (e.g. visual hallucinations), nausea, orthostatic hypotension and somnolence
Adverse effects managed by lowering the dose of levodopa
What is the treatment for dementia in Parkinson’s disease?
Dementia is a late feature
> 80% have dementia after 10-20 yrs. from diagnosis
Cholinesterase inhibitors - donepezil, rivastigmine
What does this scan show?
Basal ganglia haemorrhage with intraventricular extension
Primary IVH (i.e. haemorrhage confined to ventricular system) is very uncommon - 3% of all intracranial bleeds
Secondary IVH more common - 40-60% ICH are associated with IVH and approx. 10% SAH. More common with hypertensive / deeper bleeds than lobar bleeds
Main complication is acute neurological deterioration secondary to obstructive hydrocephalus
Management of psychotic symptoms in Parkinson’s disease
Late feature
- exclude / treat reversible factors e.g. infection / delirium
- reduce non PD meds that may be contributing
- reduce or stop PD meds if possible in an order that balances potency with likelihood of exacerbating psychotic symptoms
Starting with anticholingers
Amantadine
Dopamine agonists
MAO-B inhibitors
COMT inhibitors
Levodopa
- if above fails - quetiapine, clozapine or pimavanserin are treatment of choice
What are the differences between MS and ADEM?
ADEM = acute disseminated encephalomyelitis
- In 75% ADEM follows a systemic viral infection (i.e. parainfectious encephalomyelitis), may not be the case in MS
- ADEM can present with fever & stiff neck, altered mental staus / consciousness, which is unusual in MS
- ADEM causes multifocal neurological symptoms (motor, sensory, cranial nerve & brainstem deficits) with rapid progression requiring early hospitalisation, while MS is typically more monosymptomatic and has a relapsing - remitting course
- oligoclonal bands in CSF are less common in MS
- More MRI lesions in ADEM than MS, larger bilateral but asymmetric white matter abnormalities
- ADEM lesions have poorly defined margins, while MS lesions tend to have better defined margins
- Multiple brain lesions of about the same age on MRI is more consistent with ADEM
- thalamic lesions are common in ADEM, and rare in MS
What is the role of deep brain stimulation in PD?
Thalamic DBS - good for tremor
Subthalamic & pallidal DBS - more global effect - allows 50% sparing of levodopa dose
Criteria for eligibility
- PD for at least 5 years
- otherwise well
- NO dementia or psychosis
- have response to dopaminergic therapy
- presence of on-off motor fluctuatings
- severe dyskinesia
- tremor that is poorly controlled
Complications
- neuropsychiatric issues
- increased suicide rate in subthalamic targeted DBS
- surgical complications
What are the clinical features of MSA?
Motor features -> Parkinsonism OR cerebellar dysfunction predominant (can be overlap & predominance can change)
Parkinsonism:
- bradykinesia, akinesia, rigity, tremor
- poor response to Levodopa
Cerebellar dysfunction
- limb ataxia, gait ataxia, oculomotor dysfunction ( gaze evoked nystagmus, impaired smooth pursuits with saccadic intrusion and / or ocular dysmetria), cerebellar dysarthria
Autonomic features
- urge urinary incontinence
- voiding dysfunction with elevated PVRs
- early erectile dysfunction
- neurogenic orthostatic hypotension
Other supportive motor features
- rapid progression within 3 years of motor onset
- moderate to severe postural instability within 3 years of motor onset
- severe dysphagia within 3 years of motor onset
- severe speech impairment within 3 years of motor onset
- unexplained Babinski
- jerky myoclonic postural or kinetic tremor
- postural deformities (e.g. anterocollis, laterocollis, camptocormia)
Other supportive non-motor features
- stridor
- inspiratory sighs
- cold, discoloured hands & feet
- erectile dysfunction
- pathologic laughter or crying
Exclusionary features
- significant response to dopaminergic medications
- unexplained anosmia
- fluctuating cognition with early visuospatial abilities
- recurrent visual hallucinations within 3 yrs. of disease onset
- dementia within 3 yrs. of disease onset
- downgaze supranuclear palsy
Diagnostic criteria
- sporadic, progressive, onset after > 30 yrs with
autonomic dysfunction AND poor levodopa-responsive Parkinsonism and/or cerebellar syndrome with supportive brain MRI features
Mechanism of action of levodopa / carbidopa
Most patients with early PD should be on levodopa monotherapy
- Levodopa (L-dopa) is main precursor in dopamine synthesis
- levodopa is combined with a peripheral decarboxylase inhibitor which blocks levodopa conversion to dopamine in systemic circulation and liver in order to prevent nausea, vomiting & orthostatic hypotension
- therefore, by preventing peripheral conversion of dopamine which does not cross the BBB, carbidopa allows a smaller dose of levodopa to achieve a therapeutic effect
- most effective drug for idiopathic PD (motor function, ADLs, QOL outcomes superior to all other drugs)
- no advantage of using levodopa with COMT inhibitor for initial therapy (role of COMT inhibitors is primarily in management of motor fluctuations)
Immediate release is the preferred initial formulation
Parkinson’s disease pharmacology
What are the features of an ulnar nerve palsy?
Ulnar nerve - C8-T1
Upper limb nerves & myotomes
Distinguishing features of Parkinsonian syndromes
What does this characteristic MRI-B finding indicate?
Hummingbird sign -> prominent midbrain atrophy in PSP with relatively preserved pons
What is the diagnostic workup for GBS?
Typical clinical syndrome PLUS LP findings sufficient for diagnosis
Typical clinical findings = acute onset progressive weakness, hyporeflexia/areflexia, history of infection in preceding 4 weeks
LP findings - isolated elevated protein / albuminocytologic dissociation
If LP does NOT show albuminocytologic dissociation, need additional investigation
- MRI spine - enhancement of nerve roots
- NCS - features of demyelination - poor or absent F waves, absent H reflexes, increased distal latencies, conduction blocks with temporal dispersion, significant slowing or absent response on nerve conduction velocities
if CSF shows pleocytosis with leucocyte count > 50 cells -> very unlikely to be GBS
What does this scan show?
L) temporal AVM
associated with a 1-4% risk of rebleeding per year
What are the most common initial manifestations of MS?
Most commonly presents as a single monosymptomatic attack due to a demyelination event
Sensory symptoms are the most common initial feature of MS
Presenting with a clinically isolated syndrome is typical of relapsing remitting MS
- Optic neuritis (21%)
- Bilateral INO (brainstem / midbrain syndrome) - impaired adduction in ipsilateral eye with nystagmus in the adducting eye)
- spinal cord syndrome (transverse myelitis)
- sensory symptoms - varying degrees of impairment in vibration & proprioception, decrease in pain & light touch sensation in distal extremities, patchy areas of reduced pain & light touch perception in limbs & trunk
What are the clinical features of optic neuritis in MS?
Typically unilateral optic neuritis
- most common visual phenomenon in MS (21%)
- painful monocular central vision loss, blurred vision, scotoma
- pain on eye movement and touch
- pain often precedes vision loss
- loss of colour vision (especially red colour) & contrast sensitivity
- Uhthoff phenomenon - worse with rise in body temp
- RAPD (Marcus - Gunn pupil) with typically normal fundoscopy initially (later the optic disc becomes pale as a result of axonal loss and resultant gliosis)
- 90% patients regain normal vision over period of 2-6 months after an acute episode of optic neuritis
Bilateral optic neuritis occurring simultaneously is rare in MS
- DDX neuromyelitis optica spectrum disease, toxic optic neuropathy, Leber hereditary optic atrophy
What is the mechanism and clinical manifestation of internuclear opthalmoplegia in MS?
Bilateral INO is highly suggestive of MS
- other brainstem lesions that cause bilateral INO include vascular lesions, Arnold-Chiari malformations, Wernicke encephalopathy
Abnormal horizontal ocular movements with slow, weak adduction of the affected eye and nystagmus of the adducting eye
Highly localising brainstem syndrome -> occurs due to a lesion in the MLF in the dorsomedial brainstem tegmentum of either the pons or the midbrain
> 2/3 of INO is due to MS or cerebrovascular disease
Brainstem infarct more likely to cause unilateral INO
Periventricular location of MLF make it susceptible to demyelination
Describe the findings in a L) sided one & a half syndrome
One and a half syndrome is caused by a large unilateral lesion involving the paramedian pontine reticular formation (PPRF) and/or abducens (CN VI) nucleus AND MLF
L) eye unable to abduct (PPRF) OR adduct (MLF). R) eye unable to adduct (i.e. INO due to damage to left PPRF) but able to abduct. R) eye may be abducted at rest / in primary gaze position (known as paralytic pontine exotropia)
With attempted horizontal gaze, only abduction of the contralateral eye remains
if the abducens nucleus is spared -> gaze palsy is evident on volitional horizontal gaze (which requires activation of PPRF), but is not evident with oculocephalic manoeuvres
Diagnostic criteria for MS
Spinal cord lesions almost as common as brainlesions in MS
MS lesions are characteristically T2 hyperintense enhancing plaques or T1 hypointense “black holes”
Active lesions enhance with gadolinium on T1 weighted mri
Characteristic regions for MS plaques - spinal, cortical, juxtacortical, paraventricular, infratentorial
Prognostic factors in MS
Development of a progressive course of MS may be the single most adverse factor influencing prognosis
Factors associated with a better prognosis
- relapsing remitting MS
- sensory symptoms or optic neuritis at initial presentation
- pregnancy is protective against MS relapses, however, increased risk of relapse in early postpartum period
What does this CTB show?
Extradural bleed
- located between periosteum and the outer layer of the dura
- 75% caused by middle meningeal artery bleed
- typically associated with head trauma & skull #
- on imaging -> biconvex, limited by cranial sutures
- can have brief lucid interval followed by loss of consciousness
- can progress to cause uncal herniation
- false localising cranial nerve palsies - CN VI palsy (ipsilateral eye adducted), CN III palsy (down & out eye, ptosis, dilated pupil), Cushing’s reflex
Scan also shows contralateral contrecoup injury
What does this MRI spine demonstrate? What are the possible causes? What are the likely clinical features?
Transverse myelitis
- inflammation of the spinal cord, typically restricted to 1-2 segments, usually in the thoracic cord
- most cases are idiopathic (up to 50% have preceeding infection, possibly resulting from an autoimmune process)
- other causes are MS and neuromyelitis optica
- symptoms develop rapidly, over the course of several hours
- lower limb UMN signs, sensory level with multimodality sensory loss, autonomic dysfunction, bladder & bowel dysfunction, back pain with radicular pain, upper limb weakness if lesion is in the cervical cord
MRI demonstrates gadolinium enhancing lesiosn extending over 1-2 segments
What does this MRI spine show? What are clinical and diagnostic features of this condition?
Neuromyelitis optica
- autoimmune disease targeting astrocytes; complement-mediated demyelination and axonal damage predominantly affecting spinal cord & optic nerve; but also brain & brainstem
- presence of anti-aquaporin 4 Ab is 75-80% sensitive and > 99% specific
Clinical hallmarks
- acute attacks of bilateral or rapidly sequential optic neuritis
- transverse myelitis with a relapsing course
- episodes of intractable vomiting or hiccups (area postrema syndrome)
- PRES
- Neuroendocrine disorders
MRI-B shows extensive demyelinating lesions spanning 3 or more segments
CSF shows neutrophilic pleocytosis and is negative for oligoclonal bands
Management
- acute attacks managed with IV methyl pred & PLEX
- long term therapy:
AZA, mycophenolate, eculizumab (humanised monoclonal Ab against complement C5) provides 93% protection from 1st relapse, inebilizumab - targets CD19 on plasmablasts as well as other B cells to directly decrease Ab production
Satralizumab - anti IL-6, efficacy in AQP4 Ab positive patients
What does this scan show?
MCA aneurysm bleed
66F is found collapsed, GCS 4, background of hypertension, diabetes, previous bowel Ca. CT brain as below. What is the likely cause of this lesion?
Pontine haemorrhage
- most commonly due to uncontrolled longstanding hypertension
- lipohyalinosis of the penetrating arteries originating from the basilar artery ; larger paramedian perforators are most common culprit vessels
- very poor prognosis
- commonly presents with acute drop in GCS due to disruption of the reticular activating system
other clinical features
- long tract signs including tetraparesis
- cranial nerve palsies
- seizures
- Cheynes stokes respiratrion
Can cause locked in syndrome
- quadriplegia
- inability to speak
- - inability to swallow
- retained cognition
- supranuclear ocular motor pathways preserved -> can blink and move eyes
- respiratory function often affected
What does this CTB show?
Osmotic demyelination / central pontine myelinolysis
What does this CTB show?
Chronic subdural bleed
Subdural bleeds most common caused by head trauma causing tearing of bridging cortical veins located between the dural and arachnoid membranes
Arterial cause for SDH is found in 20-30 % cases
Risk factors include significant cerebral atrophy, antithrombotic medications and coagulopathy
Imaging features => crescenteric shape, not limited by sutural attachments of the dura as it is subdural
acute blood = hyperdense = white
subacute bleed = similar density to adjcant parenchyma
What does this CTB show?
Hyperdense material in the anterior interhemispheric fissure raising suspicion of ruptured anterior communicatiing artery aneurysm
What determines risk of aneurysmal rupture & subsequent SAH?
Risk of aneurysm rupture is based on size
* Size >7mm
* Location: highest risk in posterior circulation
What does this MRI show?
Syringomyelia
- typically affects C2-T9 causing a central cord syndrome
- loss of pain & temp sensation bilaterally below level of lesion
- typically causes LMN weakness & atrophy of uL
- spasticity and LMN signs in lower limbs
- - loss of deep tendon reflexes
- autonomic dysfunction -excessive sweating, dysregulation, labile BP, disturbances in bowel & bladder function
