Cortical Syndromes / Neurocognitive D/O Flashcards
blind man denies he is blind. What was injured?
Blind man complains of visual hallucinations. What is injured?
(Anton’s syndrome )
- Bilateral PCA infarct
- Damages both visual cortex (blind)
- and association cortex (responsible for detecting presence of vision)
(Charles Bonet’s syndrome)
- no lesions, but lilliput hallucinations due to brain unable to process lack of visual input
Patient Findings:
- Can’t attend to multiple objects in view
- Can’t reach for objects using visual information
- Can’t visually scan
What is this caused?
where is the lesion?
Balint’s syndrome (simultagnosia, oculomotor-apraxia, optic ataxia)
Bilateral parietal-occipital damage
What ischemic injury can cause pinpoint pupils?
Pontine lesions.
Syringomyelia versus Hydromyelia
Syringomyelia: fluid-filled cavity within spinal cord that is separate from the central canal (lined by gliotic tissue)
Hydromyelia = enlargement in the central canal itself (lined by ependyma)
Top 4 most common causes for TIA in children
Congential heart diseases
sickle cell
moyamoya
possibly migraine
Mutation most commonly associated with this imaging finding
Filamin A mutation
(Nodular periventricular heterotopia)
Differentiate the following:
Orbitofrontal syndrome
Dorsolateral syndrome
Anterior cingulate syndrome
Orbitofrontal syndrome
- Region responsible for integrating emotional cues and self-assessing if behavior is appropriate
- Lesions result in
- disinhibition
- undue familiarity
- impulsivitiy
- utilization behavior
- innapropriate jockularity
Dorsolateral syndrome
- Region responsible for executive functioning and planning
- Lesions result in problems with planning, anticipating, sequencing actions, and making decisions (“A>B>C>Dorsolateral syndrome”)
- Also problems with short term memory
Anterior cingulate syndrome
- Region responsible for motivation behavior
- lesions result in apathy / Abulia (severe apathy), decreased activity, decreased spontaneous speech, and (in most severe state) akinetic mutism
Differentiate the following:
Kluver-Bucy syndrome
Temporal lobe epilepsy syndrome
Kluver bucy
- Bilateral temporal lobe lesions (especially of amygdalae)
- Symptoms = “that episode of futurama when Bender became human”
- Hypersexuality
- docility / doesn’t recognized anger
- hyperphagia / hyperorality
- “voracious exploration” (hyermetamaphorsis
- Visual agnosia
- May also have amnesia and r eceptive aphasia, so often will also meet criteria for frontotemporal neurocognitive disorder
Temporal lobe epilepsy syndrome (think anti-bender or self-obsorbed philsopophy professor)
- HypOsexuality
- Hypergraphia and micrographia
- Hyperverbality
- “emotional stickiness”
- Deepened intellectual life (philosophical / religious focus)
Patient presents for 1-8 hours of retrograde AND anterograde amnesia, but preserved sensorium (anxious, not confused)
What caused this?
What is the likelihood it will recur?
Transient global amnesia
Etiology is unclear, presumed deep white matter disease / venous congestion
3-5% recurrence in 1 year
What is damaged here?
What is important about the side?
Right Parietal lobe
Left parietal lobe lesions less commonly result in hemineglect. If so they are often temporary and mild
Dorsal versus Ventral Visual pathway
Dorsal = Where
Ventral = What
What does this suggest?
Simultagnosia
Patient is able to identify objects in NIHSS “cookie” picture, but can’t describe scene, as well as inaccurate eye voluntary eye movements toward visual stimuli.
Where is his lesion?
What else would you likely see?
Balint syndrome (bilateral parietal lesion)
Simultagnosia
Oculomotor apraxia
optic ataxia: can’t direct hand in response to visual guidance
Sensory versus semantic agnosia
Sensory agnosia: lack of recognition when object is presented to particular sensory modality (visual, tactile, auditory, olfactory)
Semantic agnosia: lack of recognition of underlying meaning of object (“this sharp flat thing with a handle is a knife”
Inability to perform particular purposive actions is calle ___
Apraxia
1) when patient is asked to mime combing hair, they place their hand on their head. This is an example of ______
2) Patient gets dressed, brushes teeth, then gets into shower. This is an example of _____
1) ideomotor apraxia
2) ideational apraxia
Patient is unable to do math problems or recognize fingers.
What is damaged?
what will he also have?
Gerstman syndrome (damage to dominant Angulate gyrus)
Acalculia
finger agnosia
Agraphia
left-right confusion
Name four key components of the reward pathway
Basic ADL’s veruss Instrumental ADL’s
Basic ADL’s = “death”
- Dressing
- Eating
- Ambulating
- Toileting
- Hygiene
Instrumental ADL’s = “shaft”
- Shopping
- housekeeping
- accounting
- Food prep
- transportation
Patient comes in for evaluation of neurocognitive disorder.
Name 8 labs you will order, and what each is testing for
- CBC (Anemia, infection)
- Electrolytes + calcium (hyponatremia, SIADH)
- Glucose (Diabetes, hypoglycemia)
- BUN / Cr (renal failure, uremia)
- TSH (hypothyroidism)
- Liver enzymes (hepatic encephalopathy)
- Vitamin B12 (low b12)
- Urinalysis (infection, urosepsis)
Patient suspected to have alzheimers versus frontotemporal lobar degeneration.
what test would you order to differentiate the two?
PET
Imaging study indicated in AIDS patient with neurocognitive disorder and why?
SPECT
Lymphoma = increased perfusion
Toxoplasmosis = decreased perfusion
PET scan in NCD patient. What does this show?
PET scan in NCD patient. What does this show?
PET scan in NCD patient. What does this show?
PET scan in NCD patient. What does this show?
Pick’s disease (frontal degeneration)
Indications for LP in neurocognitive d/o workup
(8)
Suspicion for:
Metastatic cancer
CNS infection
reactive serum Syphilis
Hydrocephalus
Age < 55
Rapidly progressive or unusual dementia
immunosuppression
CNS vasculitits
If Grandma is demented, when should you take her license away?
(6)
Level A
- Clinical dementia rating (CDR) score > 0.5-1
- 0.5 (very mild)
- moderate driving risk
- 67-85% will pass driving test
- tolerated in other groups (like teenagers)
- 1.0 (mild)
- significant driving risk; consider stopping
- 41-76% will pass driving test
- 0.5 (very mild)
Level B
- Caregiver rating of unsafe driving
Level C
- history of crashes or citations
- MMSE score = 24
- reduced driving or situational avoidance (grandma doesn’t drive in the rain or during rush-hour)
- NOTE: LACK of this doesn’t imply lack of risk (could reflect lack of insight)
- Aggressive / impulsive personality
Woman says that pharmacologic managment of agitation in her elderly demented grandmother isn’t working.
How long before you consider stopping / transitioning agent?
4 weeks
Treatment for agitation / psychosis in patient with Lewy Body Disease
(2)
Quetiapine (low dose)
Clozapine (low dose)
Man brings his mother in for alzheimer’s follow-up visit and asks what his risks are for also getting it.
What factors are associated with increased risk (6 non-modifiable, 5 modifiable) and decreased risk (1 modifiable, 2 non-modifiable)
Increase risk of alzheimers
- Non-modifiable
- Age (risk doubles every 5 years after 65)
- Family history (increases risk by 2-3 fold)
- APOE4 allele (main genetic risk factor)
- Female sex (…but primarily due to longer lifespan)
- high homocysteine levels
- less eduction (lower “cognitive reserve”)
- Modifiable
- Cigarette smoking
- head trauma
- Cerebrovascular disease
- hypertension
- exposure to toxic chemicals
Protective factors
- Non-Modifiable
- High N-3 fatty acids
- APOE2 allele
- Modifiable
- Physical activity
Patient diagnosed with alzheimers asks how long she has.
How long is the average window between diagnosis and death?
10 years
Conceptual difference between APOE4 allele and Presenillin 1 mutation
APOE4 is risk-confering (doesn’t mean you will get it)
Presenillin 1 mutation is a mutation for an autosomal dominant condition
Pathologic findings associated with Alzheimers
A (4)
B (3)
C (1)
D (2)
- Senile (neuritic) plaques
- Location = extracellular
- 3 components
- Abnormal neuronal processes +
- Glial cells +
- amyloid beta 42 (AB-_42_) - this is the insoluable form
- neurofibrillary tangles
- Location: intracellular
- composed of ubiquitin + phosphorylated Tau
- Early neuronal loss
- Cerebral amyloid angiopathy
- amyloid-B forms plaques 9 (above) leading to small vessel vascular disease
60 year old woman with diagnosis of alzheimers
What is the chance she has a mutation?
what are the 3 possible mutations?
What chromosome are they on?
How do they lead to alzheimers?
50% of early onset alzeheimers disease is due to autosomal dominant mutations, 50% are sporadic (non-familial)
Mutations
- Proteases= cleave APP into soluable form, mutations lead to buildup of protein which triggers cell death by Ca++ influx
- Presinellin 1 (chromosome 14)
- Presenillin 2 (chromosome 1)
- Amyloid precursor protein itself (chromosome 21) can be misfolded, which is harder to digest with proteases.
Why don’t we routinely test for APOE4 mutations?
Present in 25% of population
APOE4 allele is present in 60^ of patients with NCD due to alzheimers (thus this incrases risk by 2.5 times)
How many numbers should the average person be able to keep in their memory (digit span)
seven
First histopathologic finding typically seen in alzheimers
Amyloid deposition in cortical and leptomeningeal vessel walls
Patient with dementia as well as inappropriate behavior, offensive speech, and poor hygiene
Where is her likely mutation?
17q21 (frontotemporal dementia)
Compare the following:
NCD with Lewy bodies
NCD due to parkinson’s disease
Lewy body variant of alzheimer’s disease
NCD with lewy bodies
- Cognitive impairment + parkinsonism occur together
- 20% of major NCDs (possibly second most common NCD)
NCD with parkinson’s disease
- Parkinson’s motor disease present for 12 months prior to cognitive impairment
- on spectrum with NCD with lew bodies
Lewy body variant of Alzheimer’s disease
- 40% of alzheimer’s patients have substantial lewy bodies
- This presents as a mixture of lew y body and alzheimer’s disease
You are a pathologist asked to confirm NCD with Lewy bodies
What are you looking for?
What brain sections will you examine?
Looking for lewy bodies: aggregation of alpha-synuclein, neurofilament, and ubiquitin (usually one per neuron)
- Midbrain
- Substantia nigra
- Brainstem
- locus ceruleus
- dorsal raphe
- dorsal motor nucleus of vagus
- Neocortex
- Present in many patients, though this is also seen in parkinson’s disease
Goal treatment for Both Lewy-body dementia and major NCD due to parkonsons
Cognitive (2)
motor (1)
psychosis (4)
depression (1)
- Cognitive
- Rivastigmine (FDA approved)
- Donepezil: not FDA approved but better tolerated (fewer GI a/e)
- Motor
- Sinimet and dopamine agonists
- though these are often of limited benefit and may worsen psychotic symptoms
- Sinimet and dopamine agonists
- Psychosis
- mild: consider no medication
- Mod/severe
- cholinesterase inhibitors
- Primavanserin: Specifically approved for hallucinations and delusions associated with PD psychosis
- low dose clozapine (quetiapine and olanzapine show no benefits)
- Sepression
- SSRI’s
Patient presents with shuffling gait, incontinence, dysarthria, innapropriate behavior, and uncontrolled crying / laughing.
What are 3 disorders this could cause and how what could lead you to suspect each?
How would you treat the innapropriate laughter
Suggestive of subcortical / small vessel NCD
Subtypes
- Subcortical leukoencephalopathy (aka Benswangers)
- Hypertension (80% have this)
- CADASIL
- Similar to Benswangers but younger age and NO hx of hypertension
- Lacunar infacrcts
- Due to perforators of MCA, thus will also have motor / sensory deficits
Treatment for pseudobulbar affect = Dextropethorphan / quinidine combo (nudexta)
Patient presents with concerns for frontotemporal NCD
What do you need to establish a diagnosis?
Step 1: need to meet criteria for Major NCD
Step 2: insidious and gradual
Step 3: Actual diagnostic criteria
- relative sparing of other cognitive dysfunctions (learning and memory, perceptual / motor function
Behavioral Variant:
- 3+ of the following
- behavioral disinhibition (by two cadillacs because they like the color)
- apathy / inertia
- loss of sympathy / empathy
- perseverative, stereotyped, compulsive, ritualistic behavior
- hyperorality / dietary changes
- Decline in social / cognition / executive function
Language variant
- Promient decline in language ability, form of speech, word finding, naming, grammar, comprehension
Potential trip-up:
FTD vs FTLD
Frontemporal Neurocognitive disease (NTD): clinical syndromes caused by Frontotemporal lobar degeneraations (FTLD)
FTLD can be caused by many things: Pick’s disease, ALS, mutations in various genes
Patient presents with concerns for frontotemporal dementia and the following MRI:
What would you expect to find in histology of this patient?
What would you NOT expect to find?
Large aggregates of intracellular protein, particularly tau (pick bodies)
Balooned nerons (Pick cells or neurites)
Typically no plaques or tangles
5 major genes associated with frontotemporal lobar degeneration (FTLD)
Family history of CJD
What chromosome and what gene are you thinking of?
Prion gene (PRNP) on chromosme 20
Classic versus variant CJD:
Median age @death
Median duration
Differences in signs / symptoms
EEG findings
MRI Features
Neuropathology / Immunology notes
Lymphoid involvement
Patient does not recognize his hand as his own.
What are 3 causes for this?
Alien Hand Syndrome
“hail a CAB with your alien hand”
- *C**orpus Callosum Lesion
- *A**nterior cerebral artery Infarct
- *B**asal ganglia degeneration (corticobasal syndrome)
How do you differentiate a patient with cortical blindlness versus pre-geniculate lesions?
Cortical blindness DO have a pupillary light reflex
Patient routinely gives approximate but incorrect answers
“2+2 = 5”
What type of disorder is this
Ganser syndrome = dissociative disorder
Patient doesn’t feel symptoms are a problem = _________
Patient doesn’t recognize problems at all = __________
Anosodiaphoria (aka La belle indifférence)
Anosognosia
Dyslexia trip-up
Cataplexy
versus
Catalepsy
Cataplexy: sudden loss of tone following an emotion (laugh or fear)
Catalepsy: remain in position in which they are placed
Term for innapropriate jockularity
Witzelsuct
Paraphasias:
- Patient says “Pale” instead of “nail”
- Patient says “nail” instead of “hammer”
- Patient says “Shoe” instead of “hammer”
- Phonemic / literal paraphasia
- Semantic paraphasia
- Remote paraphasia
Patient presents with dysarthria, dysphagia, and inability to voluntarily smile, though will smile when told a joke.
What is damaged?
Bilateral anterior operculum
(Foix-Chavany-Marie syndrome)
Patient with articulate but nonsencial speech and pronounced echolalia
What is this called?
name 4 potential causes
Transcortical sensory aphasia
Possible lesions:
- Dominant MCA-PCA watershed infarct
- thalamic lesions (thalamic aphasia)
- Alzheimer’s
“Broca’s” aphasia but with intact repition
What is this called?
name two causes
Transcortical motor aphasia
Most commonly seen in:
- watershed infarcts in dominant hemishpere ACA-MCA but sparing connections betweenn broca’s and wernicke’s area
- recovering broca’s aphasia
Patient with intact speech, comprehension, and naming, but cannot repeat words back to you
What is damaged?
Internal arcuate fasiculus
(conduction aphasia)
Woman i unable to vary speech acording to her emotional state
What is the lesion?
Non-dominant posterior inferior frontal gyrus
(Amelodia or affective motor aprosodia)
Patient is unable to understand the emotional / tonal variances in speech
What is damaged?
non-dominant posterior superior temporal gyrus
Weird delusions roundup
- Patient believe’s her loved ones have been replaced by imposters
- Patient believes multiple people are in fact the same person in different disguises
- Patient believes two individuals have swapped identities even if they look like their previous selves
- Patient similar to question 1, but also with objects
- Patient believes they are dying or dead
- Patient believes they are pregnant
- Capgras syndrome
- Fergoli’s syndrome
- intermetamorphosis
- Reduplicative paramnesia
- Cotard’s delusion
- Pseudocyesis
Patient with left hemiparesis as well inability to simultaneous double stimulation (visual and tactile)
What two other sensory findings could you also see?
(right MCA infarct)
- Imparied two-point discrimination
- agraphetesthesia (inability to differentiate object only by touch (i.e. holding keys in pocket)
Patient with previous weakness now complains of significant pain to previously weak areas
What is damaged
Contralateral thalami
(thalamic pain syndrome or Dejerine-Roussy syndrome)
Define the following terms and what is most likely damaged if there is a defect in them
- Declaritive / Explicit memory
- Nondeclarative memory
- Memory of facts / experiences
- bilateral temporal lobes
- Memory of skills and other acquired behaviors
- no specfic lesion is known to affect these
List the synucleonapthies
(4)
Amyloidopathies:
MSA
Parkinson’s diseease
dementia with Lewy Bodies
neuroaxonal dystrophies
Alcoholic patient presents with confabulation
What is damaged? Why?
Mamillary bodies (damaged by thiamine deficiency()
What disease does this patient have?
Granulovacular degeneration (Alzheimers)
What does the PCA supply?
Thalamus
Midbrain
Temporal lobes
occipital lobes
Patient presents with CL hemiparesis and IL “down and out” pupil
What was damaged?
What three other features would constitute another disease?
Weber syndrome (PCA perforators to Midbrain)
Benedikt if also:
CL hemiathetosis
CL hemichorea
CL Tremor
Patient presents with facial palsy including forehead + CL hemiparesis
What is damaged?
what other features would constitute another disease?
Millard Gubler (stroke to Basilar perforators)
considered weber if also:
IL abducen’s palsy
INO
Patient presents with loss of pain and temperature to Left face and right Body, also slurring words
What was damaged?
What two other features would you expect?
Wallenberg syndrome due to damage to PICA
Would also expect:
IL (left) ataxia
IL (left) horners
Patient presents with Right hemiparesis, Vibration and proprioception loss, and Tongue deviation
What was damaged?
Which way is his tongue deviated?
Dejerine’s syndrome (damage to Vertebral atery and ASA perforators) in Medulla
Tongue deviates to the Left (Ipsilateral lesion)
Mechanism of action:
Galantamine
- Galantamine
- Acetylcholinesterase inhibitor PLUS modulation of allosteric nicotinic acetylcholine receptors
Patient presents with multiple episodes of hemiplegia with headache, but no signs for stroke. Mother had similar symptoms
What is the mutation?
Familial hemiplegic migraine (CACNA1A)
Differentiate Balint syndrome versus Anton’s Syndrome
Balint’s syndrome:
- Optic ataxia
- oculomotor apraxia
- simultagnosia
Anton’s syndrome
- Blind person doesn’t recognize he is blined (confabulation)
Neuroimaging findings in:
Bipolar disorder (4)
first psychotic episode (3)
Schizophrenia (in general) (2)
Long-term Schizophrenia (2)
- Bipolar disorder
- reduced fractional anisotropy
- increased intensity in frontal white matter
- decreased volume in right caudate
- increased volume in hippocampus
- First psychotic episode
- slight increase in ventricular enlargement
- decreased hippocampal size
- decreased whole brain volume
- Schizophrenia (in general)
- hypofunctioning frontal cortex
- dysfunctional activation of hippocampus
- Severe and long-term schizophrenia
- deficits in gray and white matter (trend toward psoterior aspects of brain)
- severe ventricular enlargement
Brain lesions which, when damaged cause:
Abnormal fluctuations in mood
Abnormal fluctuations in behavior
- Fluctuations in MOOD
- Anterior / medial thalamus
- Fluctuations in BEHAVIOR
- amygdala
(broad strokes) what are the effects of damage to the following areas?
Anterior thalamus
Mamillary bodies (3)
amygdala
Anterior thalamus: fluctuations in mood
Mamillary bodies: psychosis, memory deficits, confabulation
Amygdala: abnormal behavior
Chromosomes implicated in familial FTD
Chromosome 9 (C9orf72)
Chromosome 17 (MAPT, GRIN)
Chrosome 3
Perinaud’s syndrome is caused by lesions of what (3)
- compression of dorsal midbrain (it’s also called dorsal midbrain syndrome)
- bilateral pretectal regions
- unilateral tegemental area
MRI findings in Dementia with Lewy Bodies
(3)
Similar to alzheimmers
- Hypometabolism in Temporoparietal corticies and medial temporal lobes
Things that may differentiate from Alzheimers
- decreased metabolic activity in occipital lobes
- Preservation of uptake of glucose in posterior cingulate cortex with adjacent hypometabolism in precuneus and Cuneus (“cingulate island sign”)
Modified Ranken Score
0 - asymptomatic
1- symptoms, but able to carry out all ADL’s
2- needs some help with ADL’s but able to care for themselves
3- not able to care for themselves but CAN walk
4- cannot walk
5- bed-bound
Pathologic abnormalities associated with:
- nonfluent primary progressive aphasia (progressive nonfluent aphasia
- Semantic Variant aphasia (semantic dementia)
- Frontotemporal dementia with motor neuron involvement
- Behavioral variant frontotemporal dementia
- nonfluent primary progressive aphasia (progressive nonfluent aphasia)
- Tau-containing inclusions
- Semantic Variant aphasia (semantic dementia)
- TDP-43 pathology
- Frontotemporal dementia with motor neuron involvement
- C9orf72
- Behavioral variant frontotemporal dementia
- Tau
- C9orf72
- TDP43
- FUS pathology
Frontal lobe syndromes
- Orbitofrontal syndrome
- Dorsolateral syndrome
- Anterior medial (cingulate) syndrome
- Orbitofrontal
- Utilization behavior
- inappropriate jocularity
- Inappropriate behavior
- Dorsolateral syndrome
- “executives like lateral thinking”
- loss of executive functions
- planning
- anticipation
- sequencing actions
- short term memory
- Anterior medial syndrome
- “medial syndrome makes you mopey, maybe even mute”
- Apathy
- decreased activity
- decreased spontaneous s;eech
- akinetic mutism
Alzheimers mutation most associated with earliest onset of AD
PSEN1 (43 years, as opposed to ~48 for APP and PSEN2)
