Neurology Flashcards
What is a unique aspect of muscle strength testing or deep tendon reflex testing in patients with Lambert-Eaton myasthenic syndrome?
Post-exercise (or post-activation) facilitation - vigorous, brief muscle activation (e.g. maximal isometric contraction of the relevant muscle for 10 to 15 seconds) can sometimes lead to temporary reappearance of previously depressed or absent deep tendon reflexes, and to temporary improvement of muscle weakness
What cancer is paraneoplastic Lambert-Eaton myasthenic syndrome most commonly associated with?
Small cell lung cancer (mostly), occasionally lymphoproliferative diseases including Hodgkin’s Lymphoma - rarely atypical carcinoid, Merkel cell etc
What are the causes of Lambert-Eaton myasthenic syndrome?
- Paraneoplastic phenomena secondary to small cell lung cancer or lymphoproliferative malignancies
- Autoimmunity secondary to thyroid disease or T1DM
- Toxic secondary to immunotherapy/immune checkpoint inhibitor therapy
What is the pathophysiology of Lambert-Eaton myasthenic syndrome?
LEMS is the result of reduced ACh release from the presynaptic nerve terminals, despite normal ACh vesicle number, normal ACh presynaptic concentration, and normal postsynaptic ACh receptors. It results from autoimmunity with antibodies directed at the P/Q subtype of Voltage Gated Calcium Channels which interferes with the normal calcium influx required for ACh release
Is the age of onset of paraneoplastic Lambert-Eaton myasthenic syndrome younger or older than non-paraneoplastic LEMS?
Older
What percentage of Lambert-Eaton myasthenic syndrome is paraneoplastic?
50%
What are the key clinical features of Lambert-Eaton myasthenic syndrome
Consider in patients presenting with proximal muscle weakness, dry mouth, hyporeflexia, and any combination of oropharyngeal muscle weakness or ptosis
Key features:
1. Slowly progressive proximalmuscle weakness (lower extremity > upper extremity) - typically describe an alteration in gait or difficulty arising from a chair or managing stairs
- usually symmetrical
- may describe muscle pain/stiffness/cramping or fatigability
- degree of weakness on exam usually less than would expect based on disability
- usually limited muscle atrophy
- Distinctive autonomic findings
- dry mouth
- sluggish pupillary response
- erectile dysfunction - Smattering of oculobulbar findings
- typically less severe or striking than in myasthenia gravis
- ptosis or diplopia are most common
- excessive or paradoxical eyelid elevation with sustained upward gaze - Depressed or absent deep tendon reflexes
- classical feature is “post-activation facilitation” which refers to recovery of lost deep tendon reflexes or improvement in muscle strength with vigorous, brief muscle activation - Respiratory failure
- often late in illness
- need to consider in differential diagnosis of patients presenting with neuromuscular respiratory failure
How do you diagnose Lambert-Eaton myasthenic syndrome?
Electrodiagnostic studies, including repetitive nerve stimulation (RNS), and anti-P/Q-type voltage-gated calcium channel (VGCC) antibody testing
The diagnosis of LEMS is confirmed on high-frequency RNS by a reproducible postexercise increase in compound muscle action potential (CMAP) amplitude of at least 100 percent compared with pre-exercise baseline value
A high titer P/Q-type VGCC antibody result is strongly suggestive of LEMS in the appropriate clinical setting -However, P/Q-type VGCC antibodies are present in a variety of clinical situations where LEMS is not present.
Is a high titre of P/Q-type VGCC antibodies diagnostic of Lambert-Eaton myasthenic syndrome?
No - whilst present in approximately 85 to 95 percent of patients with LEMS and considered confirmatory if clinical and electrophysiology features of LEMS are also present they are also found in a variety of other conditions/clinical situations where LEMS is not present including: healthy control patients, in patients with myasthenia gravis, motor neurone disease, other malignancies
What percentage of patients with Small Cell Lung Cancer also have Lambert-Eaton myasthenic syndrome as a paraneoplastic syndrome?
3%
What test should you order in patients diagnosed with Lambert-Eaton myasthenic syndrome?
CT chest, abdomen, and pelvis looking for malignancy
Also consider:
1. Magnetic resonance imaging (MRI) of the brain and/or spinal cord should also be obtained if there are focal neurologic symptoms or signs suggesting involvement of the central nervous system (CNS).
- 18-F fluorodeoxyglucose positron emission tomography (FDG-PET) if high risk for malignancy but CT scan non-diagnostic
What factors are associated with a higher risk of SCLC in Lambert-Eaton myasthenic syndrome?
A high Dutch-English LEMS Tumour Association Prediction (DELTA-P) score
And
Presence of SOX antibodies
How do you treat Lambert-Eaton myasthenic syndrome?
Symptomatic management:
- Mild weakness - monitor only
- Moderate to Severe weakness - Amifampridine or pyridostigmine
Refractory disease:
- IVIG
- Prednisolone
- Azathioprine
- Mycophenolate
- Rituximab
How does Amifampridine for the treatment of Lambert-Eaton myasthenic syndrome work?
Amifamipridine blocks potassium channels which significantly prolongs the presynaptic nerve terminal membrane depolarization, enhancing calcium entry and thereby improving the release of acetylcholine.
What are the main side effects of Amifampridine?
Perioral and extremity paraesthesiaes
Headache
Nausea
Abdominal pain
Diarrhoea
Elevated liver enzymes
Seizures
What are the main side effects of Amifampridine?
Perioral and extremity paraesthesiaes
Seizures
Headache
Nausea
Abdominal pain
Diarrhoea
Elevated liver enzymes
Is the presence of Lambert-Eaton myasthenic syndrome a good or poor prognostic marker in Small Cell Lung Cancer?
Good - the presence of LEMS in SCLC is associated with prolonged survival
Does treatment of small cell lung cancer result in resolution of Lambert-Eaton myasthenic syndrome in those patients with paraneoplastic LEMS?
Not necessarily - evidence of partial remission in weakness or EMG-abnormalities but often weakness persists despite SCLC treatment
What non-pharmacological measures are there for the management of neurogenic orthostatic hypotension?
- Remove offending medications
- Increase oral fluid and salt intake
- aim 1.5-3L fluid daily
- aim 6-10g salt daily - Compression stockings
- Modify activities
- arise slowly
- measures to clench abdominal and leg muscles when standing
- avoid valsalva eg coughing, constipation etc
- limit walking in hot weather
- increase head of bed to 30-45deg (decreases nocturnal diuresis)
- cardiovascular exercise - can be seated or swimming
Also important to:
1. Treat intravascular volume depletion
2. Address underlying medical conditions eg anaemia, CVD, adrenal insufficiency
What is the pharmacological treatment of neurogenic orthostatic hypotension?
- Fludrocortisone
- Sympathomimetic eg midodrine or droxidopa
- atomoxetine - a noradrenaline uptake inhibitor
What is the effective dose range and main issues with Fludrocortisone treatment for neurogenic orthostatic hypotension?
Fludrocortisone is a synthetic mineralocorticoid that increases sodium and water reabsorption by the kidneys therefore increasing effective circulating volume and blood pressure in all positions.
Starting dose = 50micrograms
Max dose = 200 micrograms (little benefit going above this)
Takes 5-7 days to take effect so don’t make dose adjustments more frequently than weekly
Main side effects are:
1. Hypokalaemia
2. Ankle oedema
3. Supine hypertension
Long term, fludrocortisone exacerbates hypertension and organ damage, including left ventricular hypertrophy, congestive heart failure, and kidney failure and is associated with a higher risk of all-cause hospitalization in patients with nOH
What is the “escape phenomenon” that occurs with Fludrocortisone therapy?
After a few weeks of Fludrocortisone therapy, blood volume returns to pre therapy levels but a pressor response remains (presumably due to increased vascular resistance) which may mediate its long term adverse effects
How does Midodrine work?
Midodrine is a prodrug that is metabolised to desglymidodrine, the active alpha-adrenergic agonist. It is rapid absorbed in the GIT, does not cross the blood brain barrier and causes both arterial and venous vasoconstriction
What are the main side effects of Midodrine therapy?
Supine hypertension
Piloerection
Pruritis
GI symptoms
Urinary retention
What is the effective dose range of Midodrine?
2.5mg to 10mg TDS
What are the core clinical features of Dementia with Lewy Bodies (DLB)?
- Cognitive fluctuations
- Recurrent visual hallucinations
- REM sleep disorder
- 1 or more Parkinsonism features eg
Bradykinesia
Rest tremor
Rigidity
Supportive clinical features:
- Sensitivity to antipsychotic agents
- Postural instability
- Falls
- Syncope
- Autonomic dysfunction
- Delusions
- Non-visual hallucinations
- Apathy
- Anxiety
- Depression
Which core clinical features typically occur early and persist in Dementia with Lewy Bodies?
Fluctuating cognition
Recurrent visual hallucinations
REM sleep disroder
Is DLB or AD more likely to present as amnestic mild cognitive impairment?
AD
What is the aetiology of DLB?
Unknown
Almost all cases are sporadic although occasional familial clusters ?related to alpha-synuclein gene on chromsome 4 and apolipoprotein E e4 allele
What is the pathophysiology of DLB?
It is a neurodegenerative disease characterised by the accumulation of Lewy Bodies in vulnerable sites (thereby mimicking the pathology of Idiopathic Parkinson’s disease).
Lewy Bodies are composed of alpha-synuclein protein - this protein normally transports synaptic vesicles and synaptic plasticity
Is co-existing Alzheimer’s dementia pathology common in DLB?
Yes, overlap syndrome or coexistent disease is very common and often results in an atypical clinical syndrome
Vascular dementia is also present in up to 1/3rd of patients
Neurofibrillary tangles tend to be less severe in DLB than typical AD
What are the typical (neuro) biochemical abnormalities in DLB?
Cholinergic deficit
Dopaminergic deficit
How do you differentiate Parkinson’s disease dementia from DLB?
Can be complicated and difficult
Depends mostly on relationship of timing of dementia to motor symptom onset
DLB if dementia present at symptom onset or within 1 year of Parkinsonism onset whilst Parkinson’s disease dementia if parkinsonism present >1yr before onset of dementia
What is the definition of dementia?
A progressive cognitive decline of sufficient magnitude to interfere with normal social or occupational functions or with usual daily activities
What do fluctuations in cognition, attention and arousal look like in patients with DLB?
Delirium-like
Episodes of inconsistent behaviour
Altered attention
Incoherent speech
Staring/zoning out
Daytime drowsiness/lethargy
Disorganised speech
What are the typical features of hallucinations in DLB?
Complex visual hallucinations that may resemble children or small animals
How does REM sleep behaviour disorder in DLB manifest?
Excessive jerking and complex movements during REM sleep eg falling out of bed, kicking, punching, jumping up, running, talking, yelling, swearing
Duration is brief and patients regain full awareness when they wake
Why is REM Sleep disorder important to identify in DLB?
Because it is drug-responsive
Also, 90% of patients diagnosed with idiopathic REM sleep disorder eventually develop DLB or another synucleinopathy
What blood tests should be performed for all cases of suspected dementia?
TSH - hyper/hypo-thyroidism
B12 - B12-deficiency induced dementia
FBC - to exclude anaemia
eLFTs - to assess major organ failure
Folate - folate def
Syphillis
Urinalysis - exclude UTI
HIV - HIV infection
Urine drug screen - exclude drug abuse
What structural imaging feature is characteristic of DLB?
There are none
How might Functional Dopamine transporter imaging with ioflupane (I-FP-SPECT) help differentiate between DLB and AD?
Typically normal in AD
May show low striatal activity in DLB or Parkinson’s
Note reduced dopamine transport uptake in basal ganglia sens 78% and 90% spec for DLB relative to AD
What finding on FDG-PET may be related to DLB (correlates with visual cortex pathology at autopsy)
Occipital hypometabolism
What finding on EEG may be a useful biomarker of DLB?
Evidence of prominent posterior slow-waves with periodic fluctuations in the pre-alpha/theta range
What finding on polysomnography may be indicative of DLB?
REM sleep disorder without atonia
What clinical features are usually absent in AD but present in DLB?
REM sleep disorder
Motor symptoms
What imaging features may be present on SPECT/PET in AD?
Decreased perfusion in temporoparietal region
What features may suggest Frontotemporal dementia rather than DLB?
Earlier onset eg in 50s
Rapid progression
Impulsivity
Socially inappropriate
Emotional lability
Personality changes
Blunting of verbal and language skills
Apathy and self-neglect
Parkinsonism in FTD often associated with eye movements (eg PSP) or asymmetric onset (eg CBS)
Imaging
CT/MRI -B - atrophy of frontal lobes
SPECT/PET - reduced brain activity in frontal and temporal lobes
What features may suggest Prion disorders rather than DLB?
Rapidly progressive dementia
Myoclonus and gait disorder and occasional visuospatial impairment
Diffusion weighted MRI - basal ganglia, thalamic, cortical changes
CSF - 14-3-3 protein
EEG - characteristic periodic complexes
How do you treat DLB?
Supportive care incl education, support, future planning, discussion re advanced care plans, legal matters, driving restrictions
Environmental review eg home safety evaluation, falls prevention, safe sleeping environment
Support for family and carers
Non-pharm mx
- CBT - improve cognition and behavioural disturbance + reduced anxiety/depression
- exercise - improve cognitive decline, ADLs, motor disturbances
Pharmacological mx
1st line = cholinesterase inhibitor (eg donepezil, rivastigmine, galantamine)
2nd line =NMDA receptor antagonist (eg memantine) - but evidence weak
What are some common adverse effects of cholinesterase inhibitor use?
N&V
Hypersalivation
Vivid dreams
Drowsiness
Orthostatic hypotension/syncope
Weight loss
Runny nose
Muscle cramps
Why should you try to avoid antipsychotics in DLB?
They are associated with an increased mortality and adverse effects
- rigidity
- immobility
- confusion
- sedation
- postural falls
- weight gain
- diabetes
Should avoid typical antipsychotics particularly
If you do choose an antipsychotic in DLB, which one is best?
No evidence supporting the use of a particular atypical antipsychotic
Quetiapine = well tolerated incl that it does not worsen motor function but uncertain efficacy
Risperidone = improves agitation but assoc with extra-pyramidal side effects
Clozapine = effective, ?tolerability
How do you treat REM sleep behaviour disorder in DLB?
Clonazepam
OR
Melatonin
Do you treat DLB with Levodopa?
Not usually - due to possible worsening of cognition, hallucinations and behaviour only tend to treat if motor symptoms are severe and interfere with ADLs
Response is seen in 1/3rd patients
Younger patients seem to respond better
Benefit for limited duration only
What are the main complications of DLB?
Aspiration pneumonia
Institutionalisation
Dysphagia
Antipsychotic sensitivity
Urinary incontinence
Falls
Elder abuse
What is the median survival of patients with DLB post-diagnosis?
5 years
What is the second most frequent primary neurodegenerative brain disease in adults <65 years of age?
Frontotemporal dementias - after Alzheimer’s disease
Is FTD more commonly diagnosed in people <65yo or >65yo?
> 65yo - whilst typical early onset, does not imply FTD is an exclusively early-onset form of dementia
Which gene mutations are implicated in inherited cases of FTD?
MAPT (microtubule-associated protein)
GRN (progranulin)
C9orf72 (chromosome 9 open reading frame 72)
What is the most common cause of genetic FTD?
C9orf72
(chromosome 9 open reading frame 72)
What are the major molecular subtypes of Frontotemporal lobar degeneration (FTLD)?
FTLD-tau (36-50%)
FTLD-TDP/FTLD-U (50%)
FTLD-FET (4%)
What are the subtypes of FTLD-tau (tauopathies - due to abnormal accumulation of hyperphosphorylated tau)
Pick’s disease
Corticobasal degeneration
Progressive supranuclear palsy
Globular glial tauopathy
Autosomal dominant familial tau
What are the hallmark lesions in FTLD-TDP?
Neuronal cytoplasmic inclusions and dystrophic neurites that are immunoreactive for TDP-43, ubiquitin, and p62, but negative for other neurodegenerative disease-related proteins
ie tau-negative, ubiquitin positive inclusions; so called TDP-43 proteinopathies
What genes are associated with FTLD-FET ?
FUS (fused in sarcoma)
EWS (Ewing’s sarcoma)
TAF15
How can FTD be classified?
Clinically:
Behaviour variant FTD
vs
Primary progressive aphasia
OR
Behavioural presentation:
Apathetic
vs
Disinhibited
vs
Sterotypic forms
OR
Whether manifests with Parkinsonism
FTD with Parkinsonism
vs
FTD without Parkinsonism
OR
Tauopathies
vs
TDP-43 proteinopathies
What are the common clinical features that may be found in FTD?
Insidious onset of coarsened personality and changes in social behaviour and habits
Gradually progressive loss of language fluency or comprehension
Progressive self-neglect and abandonment of work, activities, social contacts
Which comes first in FTD - personality changes or memory impairment?
In FTD, changes in personality, language, habits, and activity generally precede the development of memory impairment, disorientation, or apraxias
What other conditions are important to exclude in a patient suspected of having FTD?
Hyperthyroidism (presentation can mimic FTD)
ALS - characterised by progressive asymmetrical weakness of spinal or bulbar muscles which may be accompanied by bulbar weakness
Normal Pressure hydrocephalus
Primary brain tumour (frontal lobe)
HIV dementia
Neurosyphillis
What CSF marker may have value in diagnosing FTD?
NfL (neurofilament light chain)
NPTX2
Higher levels of NfL and amyloid + Lower levels of amyloid precursor protein (sAPPb) may help distinguish FTD from AD
What imaging abnormalities are often present in FTD?
bvFTD - atrophy (on MRI) and hypometabolism (on FDG-PET) in prefrontal cortex and anterior temporal lobes with relative sparing of more posterior regions of the brain incl occipital lobe
semantic dementia - atrophy (on MRI) and hypometabolism (on FDG-PET) in temporal lobes
Primary progressive aphasia - focal patterns of atrophy (on MRI) and hypometabolism (on FDG-PET) in left posterior frontal lobe
Most of the gene mutations associated with FTD are present in patients with strong family history, but which one can be seen in sporadic disease?
C9orf72
Which patients with FTD should have genetic testing performed?
All patients with probable or possible bvFTD
Suspected bvFTD with strong psychiatric features and 1+ affected family members
Is there any drug treatments indicated for treatment of FTD?
No - no evidence for effectiveness of drug treatment and in fact, acetylcholinesterase inhibitors and memantine (NMDA receptor antagonist) may hasten cognitive decline or worsen behavioural symptoms
Should try to limit medication use
What antibiotics are associated with psychotoxicity?
Fluoroquinolones
Do patients with FTD or AD have shorter survival and faster rates of cognitive and functional decline?
FTD
Which gene mutations in FTD are most likely to result in FTD with Parkinsonism?
MAPT gene mutations
Which gene mutations in FTD are most likely to result in behavioural FTD phenotype associated with marked impairments of semantic knowledge ie semantic dementia?
GRN gene mutations
Mutations in C9orf72 gene in FTD are most likely to result in which subtypes/variants?
bvFTD
FTD with motor neuron features
What is the typical regional atrophy pattern of Alzheimer’s dementia?
Temporal (incl hippocampal) and parietal with sparing of sensorimotor strip + occipital lobe
What is the typical regional atrophy pattern of bvFTD?
Prefrontal and anterior temporal lobe
What is the typical regional atrophy pattern of Huntington disease?
Head of the caudate
What is the typical regional atrophy pattern of nonfluent variant primary progressive aphasia?
Dominant perisylvian
What is the typical regional atrophy pattern of PSP?
Diminished midbrain anteroposterior diameter
What is the typical regional atrophy pattern of semantic variant primary progressive aphasia?
Anterior inferior temporal lobes
Is hippocampal atrophy pathognomonic for AD?
No - can also be seen in mesial temporal lobe sclerosis, temporal lobe epilepsy, certain vascular insults
What is the typical triad in Normal Pressure Hydrocephalus?
Dementia
Gait disturbance
Incontinence
What is the role of LP / CSF analysis in the evaluation of dementia?
LP is typically performed to exclude infectious, inflammatory or neoplastic process.
Often only in the setting of a rapidly progressive ԁеmentiа, or in a younger patient, or as a follow-up to another abnormality identified on clinical history (eg, HIV), examination, laboratory testing (eg, abnormal syphilis serology), or ոеսrοimagiոg (eg, meningeal enhancement)
CSF biomarkers have a limited role in diagnosis of AD or DLB
What is a Prion Disease?
A group of uniformly fatal neurodegenerative diseases characterised by progressive dementia and motor dysfunction
Also known as transmissible spongiform encephalopathies
What percentage of Prion diseases are genetic?
10-15%, rest are sporadic. Very rare to be acquired
What is the lifetime risk of developing a Prion disease?
1 in 30,000 to 1 in 60,000
Genetic mutations on what chromosome may cause genetic Prion disease?
Chromosome 20
Gene mutations encoding PRNP (endogenous prion protein)
How are acquired cases of Prion disease usually transmitted?
Either iatrogenic via medical procedures eg cadaver-derived corneal grafts, dura mater grafts or neurosurgery involving prion-contaminated surgical instruments (can be very hard to sterilise)
Or
Ingestion of prion-contaminated beef
Or
Transfusion of affected blood products
What is the pathophysiology of Prion diseases?
Prion diseases are caused by the conversion of healthy endogenous prion proteins (largely alpha-helix structure) into a pathogenic form (largely beta-pleated sheet)
Once converted, these misshapen proteins initiate a transformational cascade converting other nearby prion proteins
The resulting accumulation of pathogenic prions in the CNS causes nerve cell injury and eventual death
During the process of nerve cell injury, fluid filled vacuoles appear in the dendritic tree of neurons - has a spongiform appearance on microscopy hence alternate name for Prion diseases
- they are considered a hallmark characteristic of Prion disease
Prion disease secondary to consumption of Bovine Spongiform Encephalopathy (BSE, mad cow disease) contaminated beef causes what subtype of Prion disease?
Acquired (rather than sporadic or genetic)
Also called variant CJD
Fatal familial insomnia is a type of genetic prion disease - what are the clinical hallmarks?
Begins with increasing insomnia, anxiety and dysautonomia
Progresses to ataxia, hallucinations, weight loss, dementia and eventual death
How does sporadic Crutzfeldt-Jakob disease typically present?
Subacute (but more rapid development than most of the other forms of dementia) cognitive decline in a patient in their 60s
Cognitive -
Memory loss
Aphasia
Executive dysfunction
Motor -
Parkinsonism
Myoclonus
Limb/gait ataxia
Behavioural change incl agitation, depression
Vertigo/dizziness
Headaches
Visual - diplopia, hallucinations, distortions
How does variant CJD present differently to sCJD?
Typically affects young adults / teens (as opposed to 60 yo)
First symptoms psychiatric (profound depression) and mild cognitive impairment (whereas cognitive impairment prominent early feature in sCJD)
Later develop dementia, ataxia, painful sensory symptoms, movement disorder
May have hx of potential exposure eg consumption of beef in UK
What is the first test you should order in a patient you suspect has CJD and what is the typical abnormality?
MRI-Brain
Often demonstrates hyper intensity of cerebral cortex (cerebral ribboning), basal ganglia and thalamus on DWI and FLAIR and hypo intensity on ADC
How sensitive and specific is MRI for CJD?
Sens 92-96%
Spec 93-94%
What are the typical findings on EEG in CJD and are these sens or spec for the diagnosis?
Generalised slowing, focal or diffuse
Periodic sharp-wave complexes
Moderately specific, only 60% sens
Can CSF biomarkers definitively diagnose or rule out prion disease?
No - unclear sens and spec
14-3-3 protein (ie western blot) may be positive (but variable accuracy and guidelines shifting away from its use)
Total tau and neuron-specific enolase may be elevated and support the idea of rapidly progressive neuronal deterioration
Quaking-induced conversion (QuIC) may be positive
Other than brain biopsy, what other tissue can be sampled and be diagnostic of prion disease in variant CJD?
Tonsil biopsy
How can you differentiate CJD from DLB, AD or FTD?
Usually via MRI demonstrating typical signs of a specific condition
How can CJD be distinguished from Hashimoto’s encephalopathy?
AntiTPO and/or anti-TG antibodies may be positive in Hashimoto’s
There may or may not be assoc thyroid dysfunction
MRI will show characteristic abnormalities in CJD but not if Hashimoto’s
What is the classic triad of Wernicke’s encephalopathy?
Nystagmus
Ataxia
Memory loss
What is the classic triad of Pellagra (Vit B3 deficiency)?
Dermatitis
Diarrhoea
Dementia
What are the classic features of PSP?
Unprovoked backward falls (within first 1-3 years)
Vertical Supranuclear palsy (slow vertical saccades and difficulty with downward gaze)
Symmetric Parkinsonism incl axial rigidity and poor or transient response to levodopa
Speech or language disorders
Swallowing difficulties
Are there any approved treatments for CJD?
No
Treatment is supportive
SSRIs for mood/insomnia
Clonazepam for insomnia/myoclonus
What is the typical prognosis in CJD?
<1 year
What is the hallmark finding in PSP?
Supranuclear opthalmoparesis - but it may take 10 years to develop
Earliest manifestation = slowing of vertical saccades (ask patient to look straight ahead then follow your finger up and down - should be smooth and quick; if slow or require more than one step to reach target = suggestive)
This typically progresses to restricted saccadic range (ie inability to look fully upwards or downwards; lateral gaze less affected) - may manifest as slow, jerky movements
Interestingly, the opthalmoparesis of PSP can be overcome by oculocephalic / doll’s eyes manoeuvre
What is the classic facial expression in PSP?
Perpetual surprise or astonishment
- rare blinking, facial dystonia with eyelid retraction and gaze abnormalities
The classic phenotype of PSP is also known as ?
Richardson syndrome
What is the classic gait abnormality in patients with PsP?
A stiff, broad-based gait
May pivot quickly and become unstable “drunken sailor gait” and tend to be impulsive ie jump out of the chair “rocket sign”
(Knees and trunk extended and arms slightly abducted)
Differs from typical PD in which they demonstrate flexed posture
How is postural instability tested for in PsP?
Pull test (stand behind px and exert gentle but firm tug backwards on px shoulders)
In PSP often take multiple steps backwards to regain balance (>2 steps is abnormal) although some may “fall like a tree”
How is postural instability tested for in PsP?
Pull test (stand behind px and exert gentle but firm tug backwards on px shoulders)
In PSP often take multiple steps backwards to regain balance (>2 steps is abnormal) although some may “fall like a tree”
What clinical features suggest PSP rather than Parkinson’s disease?
Absent resting tremor
Absent, poor or transient response to levodopa
Preservation of olfaction
Oculomotor abnormalities
Absent autonomic dysfunction or visual hallucinations
What features might suggest Multisytem atrophy rather than PsP?
Younger Onset (ie in 6th decade)
Prominent early autonomic symptoms
Ultimately tho may be difficult to distinguish in early course
What features might suggest Multisytem atrophy rather than PsP?
Younger Onset (ie in 6th decade)
Prominent early autonomic symptoms
Ultimately tho may be difficult to distinguish in early course
What are the four core domains affected in PSP?
Oculomotor dysfunction
Postural instability
Akinesia
Cognitive dysfunction
