Exam 3 Deck 2 Flashcards
What is dementia?
Clinical syndrome marked by progressive cognitive impairment in clear consciousness
Represent a decline from previous level of functioning
Involves multiple cognitive domains
Interferes significantly with social or occupational functioning
Small percentage is reversible
(Common in elderly)
What is Major Neurocognitive Disorder?
Dementia
What are the diagnostic criteria for dementia (major neurocognitive disorder)?
- Significant cognitive decline from previous level of performance in one or more cognitive domains
- Cognitive defects interfere with independence
- They do not occur exclusively in context of delerium
- Not explained by something else
What is the course of dementia?
Generally insiduous onset with duration of 6 months to 15 years
Progressive cognitive and functional decline that eventually leads to death
Neuropsychiatric symptoms typically worsen with dprogression
What is the prognosis for dementia?
Leads to death
Identifying correctable causes can improve symptoms
What is the number 1 risk factor for dementia?
AGE
Which gender suffers from dementia more?
Females
What are risk factors for dementia?
Age
Female
Vascular (HTN, CV disease, obesity, hyperlipidemia, CHF, A.fib. …)
Environmental (alcohol, diet)
Genetics
What are some factors associated with the reversal of dementia or the slowing of its progression?
Education
Social networks
Cognitive stimulating activities/leisure activities
Exercise
Being male
Statins, perhaps; broadly, control of vascular risk factors
What non-cognitive symptoms are observed in dementia?
Affective and motivational symptoms
Psychotic symptoms
Disturbances of basic drives
Inappropriate/disinhibited behaviors (wandering)
Sleep disturbance
What symptoms of dementia lead to increased caregiver burden/stress, increased institutionalization, increased cost of care, increased bad outcomes for caregivers, increased bad outcomes for elders (abuse, neglect), danger, and worse medical care?
Non-cognitive symptoms-
affective & motivational, psychotic symptoms, disturbances of basic drives, socially inappropriate/disinhibited behaviors (aggression, wandering), sleep disturbance and neurological findings.
What are features of cortical dementia?
Memory impairment (recall and recognition)
Language defecits
Apraxia
Agnosia
Visuospatial deficits
What are features of subcortical dementia?
Greater impairment of recall memory
Decreased verbal fluency without anomia
Bradyphrenia (slowed thinking)
Depressed mood
Affective lability
Apathy
Decreased attention/concentration
What are some features that distinguish cortical from subcortical dementias?
Cortical have recall and recognition memory impairments; Subcortical is more recall impairments
Cortical dementias lack prominent motor signs; subcortical typically feature them
What are some etiologies of dementia?
Alzheimer’s
Dementia with Lewy bodies
Vascular
Frontotemporal (Pick’s disease)
Mixed
What is the most common cause of dementia?
Alzheimer’s
followed by Lewy Body / Vascular
What are core features of lewy body dementia?
Fluctuating cognition with pronounced variations in attention and alertness
Visual hallucinations
Spontaneous parkinsonism
What type of dementia presents with recurrent visual hallucinations and spontaneous parkinsonism?
Lewy Body Dementia
What is the major constituent of the cause of the dementia that causes visual hallucinations and parkinsonism?
α-synuclein - This is Dementia with Lewy Bodies
What causes vascular dementia?
Ischemic or hemorrhagic injury to the brain, consequence of cerebrovascular or cardiovascular disease
What are etiologies of vascular dementia?
Stroke
Small vessel ischemic disease
Hemorrhage
Chronic hypoperfusion
Genetic
Cerrebral amyloid angiopathy
What are frontotemporal dementias?
Group of disorders with shared clinical features - deterioration of language and personality changes
Includes Pick’s Disease
Earlier onset than AD, with insiduous onset, gradual progression
Executive Dysfunction, attentional defecits, loss of insight
3-5 years before death
TAUOPATHY
What do you find on neuropathology of frontotemproal dementials?
Atrophy and Pick bodies (tau-containing deposits)
What type of dementia is seen here?
Frontotemporal - Atrophy!
What characterizes Creutzfeldt-Jakob Dementia?
Prion disease that is invariably fatal
Incidence = 60-64 years
Rapidly progressive
Myoclonus, extrapyramidal signs, cerebellar signs
How do you evaluate a patient with dementia?
Physical and mental status/cognitive exams
Lab testing to check for reversible etiologies (thyroid, LFTs, metabolic, CBC, Vit. B12, folate, infectious…)
Maybe CXR, EKG, Brain imaging, EEG…
What are the activities of daily living?
Toileting
Bathing
Dressing
Eating
Transferring
What are the independent activities of daily living?
Telephone use
Shopping
Laundry
Transportation
Food prep
Managing meds
Finances
Housekeeping
What are non-pharmacological treatments of dementia?
Psychotherapy, behavioral management, cognitive skills training, education, legal & financial planning, safety, caregiver support
What are some pharmacological treatments of dementia?
Antipsychotics if symptoms exist
Anticonvulsants, SSRIs for behavioral disturbance
SSRIs for depression
Cholinesterase inhibitors (i.e. donepezil)
NMDA Receptor antagonist (Memantine)
Anti-amyloid therapies (experimental)
What is delerium?
Disturbance of consciousness with reduced ability to focus, sustain, or shift attention
Change in cognition not better accounted for by dementia
Over short period of time and fluctuates
Epidemic in hospitalized patients
Where do you most commonly see delerium?
Hospitalized patients
What is psychology?
Study of the mind, occuring partly via the study of behavior
What is psychological testing?
Formal assesment of emotionality, intellecutal abilities, personality, and psychopathology
What is neuropsychology?
Specialized discipline within psychology that mostly focuses on cognition in relation to the effects of brain damage or organic brain disease
What is neuropsychological testing?
Formal assessment of cognitive function, behavior, functional impairment - helps localize lesion
What is an objective psychological test?
Responses are analyzed according to universal standard
Minnesota Multiphasic Personality Inventory
Intelligence Tests/WAIS
Achievement (SAT, MCAT, USMLE, etc)
What is a projective psychological test?
Personality test designed to let a person in an open ended way respond to ambiguous stimuli, revealing hidden emotion and internal conflicts
Rorschach
Thematic Apperception Test
Sentence Completion Test
What does the Patient-Health Questionaire (PHQ-9 or PHQ-2) screen for?
Depression
What are some neuropsychological tests?
WAIS-R, Stanford-Binet (IQ tests)
Neurocognitive battery (e.g. Halstead Reitan) that assesses various aspects of cognition
What does IQ measure?
Mental Age/Chronological Age x 100
What defines mental retardation on IQ?
IQ < 70
What is the borderline intellectual functioning score on IQ?
70-79
What is the WAIS-R?
Adult intellegence test
What is the Stroop Test?
Changing words and colors to measure selective attention, cognitive flexibility, problem solivng, processing speed (executive functioning)
e.g.
What is the Wisconsin Card Sorting Test?
Tests set-shifting (executive function)
Sensitive to frontal lobe dysfunction (DLPFC in particular)
What tests are useful in assessing executive function?
Stroop Test
Wisconsin Card sorting
What is the California Verbal Learning Test?
Tests ability to acquire, store and retrieve verbal information for more than a few minutes
What is the MMSE?
Bedside dementia screen - look for changes over time
Does not assess executive function
What is the MoCA?
Montreal Cognitive Assessment
Good for testing dementia - includes executive function
What are cognitive changes seen in normal aging?
Slowed info processing
Decreased info retreival
Decreased fine motor coordination
Learning, verbal fluency and abstraction are in tact
What are physiologic changes associated with aging?
Innate immune function (increased MHC in brain)
Reduced plasticity
What are neuropathologic changes seen in normal aging?
Decreased volume and weight - widened sucli and large ventricles
Loss/shrinkage of neurons
Lipofuscin pigment accumulation and maybe neurofibrillary tangles
Are lipofuschin pigments normal to be found in an aging brain?
Yes
What is an example of amyloidoses?
Alzheimer’s disease
What is an example of a tauopathy?
Progressive supranuclear palsy
Pick’s Disease
What is an example of synucleinopathy?
Parkinson’s Disease
Dementia with Lewy Bodies
Multiple System Atrophy
What is an example of TDP-43 proteinopathies?
Frontotemporal lobar degeneration
Amyotrophic Lateral Sclerosis (ALS)
What is found neuropathologically in AD?
Neurofibrillary tangles (tau- intracellular) and neuritic plaques (amyloid core- extracellular)
What is a major distinction between neurofibrillary tangles and neuritic plaques?
Neurofibrillary tangles are tau protein aggregates intracellularly
Neuritic plaques are plaques found extracellularly with amyloid core
What finding is essential for a diagnosis of AD?
Dementia
What characterizes Pick’s Disease (Fronto-temporal lobar degeneration)?
Lobar atrophy, particularly in the frontal, anterior temporal areas
Deposition of Pick bodies - round structures in the neuronal perikaryon
Tau protein aggregates, as well as ubiquitin and tubulin
What are “Balloon” or “Pick” cells?
Chromatolytic neurons seen in Pick’s Disease (Frontotemporal lobar degeneration)
What characterizes ALS?
UMN and LMN degeneration
Pathology findings include bunina bodies in anterior horn cells (small, eosinophilic)
Contian hyaline inclusions and skeins seen in immunohistochemistry
When do you see skeins?
ALS
What characterizes progressive supranuclear palsy?
Supranuclear opthalmoplegia, akinesia, rigidita, nuchal dystonia, pseudobulbar palsy and dementia
Neuronal loss and NF tangles in brainstem - CNIII, IV, X and XII and other structures
Different tangles than in AD
How do the neurofibrillary tangles seen in progressive supranuclear palsy differ from those in AD?
They are straight filaments rather than paired helical filaments
What is Capgras Syndrome?
Patients can recognize faces but are unable place emotional valence to them
Para-amnesia
What are focal pathologies of cerebrovascular disease?
Arteriosclrosis
Congophilic angiopathy
Aneurysm
Vasculitis
What are global pathologies of cerebrovascular disease?
Hypoperfusion
Hypoxia/anoxia
Hypoglycemia
What is a stroke?
Prolonged ischemia to vascular territory resulting in tissue necrosis
Can be caused by thromboembolus (often hemorrhagic) - particularly carotid territory
Can be caused by thrombosis (over local plaque) - particularly in posterior circulation
What is the most common cause of cerebral infarcts?
Thromboembolus - originating in the carotids
What is the most common cause of cerebral infarct in the posterior circulation?
Thrombosis
Where is the most common location of in situ atherosclerosis in the Circle of Wilis?
Posterior circulation
What are causes of cerebral hemorrhage?
Trauma
Vascular malformation (berry aneurysm)
HTN
Cereberal amyloid angiopathy
What are highly vulnerable brain regions to global brain hypoxia?
Neurons > oligodendrocytes > astrocytes
Hippocampal formation
Cortical layers 3, 5, 6 via damage to pyramidal neurons
Arterial border zone territories
What are characteristics of an acute infarct?
Pallor, edema swelling, sometimes hemorrhage
Activation of PMNs
This can lead to herniation if untreated
What are characteristics of a subactue infarct?
Macrophage infiltration - lipid laden or filled with hemosiderin
Vascular proliferation (VEGF)
Demarcation, organization, contraction
What can be seen in chronic infarcts?
Wallerian degeneration of damaged axons
Cystic cavity
What is different in brain death from vegetative states?
Brain death requires respirator
What is a vascular cause of brain death?
Diffuse cerebral edema that increases ICP
Arterial inflow ceases, while extracranial structures are still perfused
Patient requires respirator
NO functional recovery
What is the prognosis for a brain dead patient?
Poor - no functional recovery
What are modifiable risk factors for stroke?
Previous stroke or TIA
HTN
Cardiac disease
Diabetes
Hyperlipidemia
CAD
Smoking
Obesity, inactivity, drugs
Oral contraceptives
What are non-modifiable risk factors for stroke?
Age over 55
Hispanicity
Diabetis
African Americanicity
Male
What is the most common cause of ischemic stroke?
Thromboembolism
Acute therapy includes thrombolysis
What is the acute therapy for most ischemic strokes?
Thrombolysis - because most commonly caused by thromboembolism
What is the ischemic penumbra?
The tissue at risk for injury, but still salvagable. The target for acute stroke therapy
What is amaurosis fugax?
Painless monocular blindness that can be caused by anterior circulation TIAs or stroke
What is the distribution of deficits seen in anterior circulation strokes/TIAs?
Face-hand-arm-leg contralateral hemiparesis and hemisensory loss
Leg more than arm in ACA; arm more than leg in MCA
In which artery, ACA or MCA does a TIA or stroke cause more leg involvement than arm involvement?
ACA (think about the homonculus)
What symptoms would a patient with a stroke or TIA to the left cerebral hemisphere present with?
Aphasia
Left gaze preference
Right visual field deficit
Right hemiparesis
Right hemisensory loss
Where could a TIA or stroke be localized in a patient presenting with aphasia, left gaze preference, right visual field deficits, right hemiparesis, and right hemisensory loss?
Left cerebral hemisphere
What symptoms would a patient with a TIA or stroke to the right cerebral hemisphere present?
Neglect (left hemi-inattention)
Right gaze preference
Left visual field deficit
Left hemiparesis
Left hemisensory loss
Where could you localize a TIA or stroke to in a patient with Neglect (left hemi-inattention), right gaze preference, left visual field deficits, left hemisensory loss and left hemiparesis?
Right cerebral hemisphere
What is the result of an internal carotid artery occlusion?
ACA and MCA syndromes
May be preceded by amaurosis fugax
What are deficits that you see in posterior cerebral artery strokes or TIAs?
Contralateral homonymous hemianopsia with macular sparing
If dominant - alexia without agraphia (can’t read, but can write)
If bilatera, can get Anton’s Syndrome
What is Anton’s Syndrome?
Bilateral posterior cerebral artery syndrome that causes patients to have blindness without knowing it
What are the characteristic signs you see in brainstem strokes/TIAs?
Crossed signs
Where do emboli occur more frequently in the cerebral circulation?
Anterior (posterior is less frequent)
What can cause cerebellar infarction?
SCA, AICA, or PICA occlusions
What is a life threatening sequellae of cerebellar infarcts?
Edema
What are lacunar strokes?
Small, sub-cortical strokes
Most common in the basal ganglia, thalamus, internal capsule, corona radiata, pons
Can cause pure motor stroke (thalamus), pure sensory stroke (posterior limb of internal capsule), ataxic hemiparesis, dysarthria
What are TIAs?
Transient ischemic attacks
By definition, symptoms last less than 24 hours
What is subarachnoid hemorrhage?
Bleeding around the brain
Usually caused by ruptured aneurysm
surgical emergency
What is needed for a definitive diagnosis of subarachnoid hemorrhage?
CT or LP
What is a berry aneurysm?
Congenital weakness aneurysm often seen in Circle of Willis
What is the most common location for a Berry aneurysm
Acomm
What is a mycotic aneurysm?
Caused by infection, usually due to bacteremia or septic embolization
What is a Charcot-Bouchard aneurysm?
Microaneurysm usually in the lenticulostriates, associated with chronic hypertension
What type of aneurysm are you likely to see in chronic hypertensive patients?
Charcot-Bouchard
What type of aneurysm are you likely to see in bacteremic patients?
Mycotic
What is the most common cause of intracerebral hemorrhage?
Chronic hypertension
Where are hemorrhages caused by hypertension most commonly found?
Thalamus
Putamen
Caudate
Pons
Cerebellum
What percentage of strokes are ischemic?
85%
Most of these result from clot occluding an artery
What are treatment options for acute stroke?
IV tPA (tissue plasminogen activator)
What drug do patients need to take for life afer having a stroke?
Aspirin - warfarin not shown to be more effective
Which cortical regions are important in autonomic control?
Insular cortex - viscero-motor and sensory cortex
Amygdala- emotional autonomic output
Anterior cingulate - goal-directed behavior autonomics
What are subcortical regions that are important in autonomic control?
Hypothalamus and pre-optic area - integrate autonomic + endocrine responses
Lateral and para-ventricular nuclei provide output to brainstem and spinal cord
What brainstem structures are important in the autonomic system?
Solitary tract nucleus - relay for visceral afferents and medullary reflexes
Ventrolateral medulla - nucleus ambiguus and dorsal motor vagus nucleus
What are the main parasymapthetic outflows?
Cranial = vagus
Sacral = sacral parasympathetic nucleus (distal GI, pelvic organs)
What is the nucleus of origin for the nerves that constrict the pupil?
Edinger-Westphal (parasympathetics of CNIII)
What is Horner’s Syndrome??
Clinical triad of:
Drooping eyelid (ptosis)
Miosis (small pupil)
Anhidrosis (lack of sweating)
Can be caused by a pancoast tumor (lesion at apex of lung)
What type of tumor can cause a Horner’s Syndrome?
Pancoast tumor (at apex of lung)
What is seen in a CN III palsy?
Down and out eye
Ptosis
Dilated pupil due to involvement of parasympathetics
What is the afferent limb of autonomic control of blood pressure?
Baroreceptors in heart and major vessels sense pressure
Chemoreceptors in carotid body sense O2 and CO2 levels
Convey this information via branches of CN IX and X to the nucleus of the solitary tract
What nucleus is important in receiving autonomic information about blood pressure?
Solitary Tract nucleus (gets info from chemoreceptors in carotid body - blood gases - and from baroreceptors)
Lesions to which areas can cause dysfunction of BP control?
Both CNS and PNS
What are sequellae of dysfunctional BP control?
Orthostatic hypotension and syncope
What brain regions are involved in the regulation of body temperature?
Preoptic area
Anterior Hypothalamus
Is sweating under sympathetic or parasympathetic control?
Sympathetic
What is hyperhidrosis?
Too much sweating
What is hyophidrosis?
Too little sweating (anhidrosis if not at all)
What provides the sympathetic innervation of the pelvic structures?
Hypogastric nerves from thoracic cord levels
What provides the parasympathetic innervation of the pelvic structures?
Sacral plexus nerves
What provides somatic innervation for pelvic structures?
Sacral spinal cord - pudendal nerve
What is overflow incontinence?
Atonic or “flaccid” bladder
Fails to empty, fills to capacity, then overflows
What is the term for a bladder that fails to empty, fills to capacity, then overflows?
Overflow incontinence
What are symptoms of overflow incontinence?
Inability to sense bladder fullness
Stress incontinence
Frequency, urgency, nocturia, UTIs, renal impairment
What are neurologic causes of overflow incontinence?
Disruption of detrusor reflex leading to de-afferented and/or weak detrusor
From cauda equina/conus medullaris
What nerve is implicated in overflow incontinence and what is its origin?
Detrusor - from cauda equina/conus medullaris
What is detrusor hyperreflexia?
Automatic or “spastic” bladder
Bladder contracts while patient is attempting to inhibit micturition
What is the term for when a bladder contracts while a patient is attempting to inhibit micturition?
Detrusor hyperreflexia (spastic bladder)
What are symptoms of detrusor hyperreflexia?
Urgency
Frequency
Nocturia
What are common neurologic causes of syncope?
Neurodegeneration (central as in Parkinsons, or peripheral as in Diabetes, amyloid)
Benign or syndromic (vasovagal, vasodepressor, postural orthostatic tachycardia syndrome)
what is orthostatic hypotension?
Caused by a ndurodegenerative disorder
Drop in BP on tilt test - may have compensatory tachycardia if early
At what stage of orthostatic hypotension do you see a compensatory tachycardia?
Early
Late you do not see it
What is vasovagal syncope?
“The common faint”
Sudden increase in vagal tone that causes bradycardia and hypotension
What is postural orthostatic tachycardia syndrome (POTS)?
Symptoms of orthostatic intolerance upon standing with increase in HR and no change in BP
Common in young women
What do we see here?
POTS
What do we see here?
Vasovagal syncope
What do we see here?
Orthostatic hypotension
What are chronic autonomic neuropathies commonly associated with?
Peripheral neuropathies
E.g. from DM, amyloid, hereditary, Sjogren’s…
What are acute/subacute autonomic neuropathies associated with?
Toxicities (chemo)
Guillain-Barre
Immune-mediated/post viral
Paraneoplastic
How do you treat orthostatic intolerance?
Reveiw meds
Salt, and water
Compression stockings
Elevate bed
Strengthen legs
Florinef midodrine
Pyridostigmine and β-blockers for POTS
What is the central controller of the ANS in the brain?
Hypothalamus - connects to cortex and nuclei in thoracic and lumbar spinal cord; sacral spinal cord; brainstem
What is HRDB?
Heart Rate response to Deep Breathing
Test of autonomic function
What is Valsalva maneuver?
Forced rapid exhalation that produces hemodynamic chagnes that tests parasympathetic and sympathetic systems
What are Central causes of ANS dysfunction?
Parkinson’s disease spectrum (PD, MSA)
Neurodegeneration
What are main peripheral causes of ANS dysfunction?
Diabetes
Amyloidosis
Hereditary with sensory loss
Connective tissue (Sjorgen’s, RA, SLE)
Toxic
Guillain-Barre
Immune
Paraneoplastic
What is the limbic system?
The vague term used to describe a variable collection of forebrain regions that are important for emotions and memory
What are the regions of the brain that are involved in the limbic system?
Hippocampus
Amygdala
Anterior thalamic nuclei
Septum
Limbic cortex and fornix
Prefrontal cortex
Nucleus accumbens
Bed nucleus of stria terminalis
Lateral habenula
What is the function of the hippocampus?
Important in memory and emotion - especially declarative memory
Necessary for new memory formation - but they are stored elsewhere
Major inhibitory control of HPA axis
Brief bursts of cortisol promote hippocampal function
Sustained bursts damage hippocampus, leading to feedforward pathological loop
What happens to a patient if you remove their hippocampus?
They develop profound anterograde amnesia
Procedural or habit memory is normal
What role does the hippocampus play in governing cortisol secretion?
Inhibitory ia HPA axis
Short bursts of cortiosl promote hippocampal function to inhibit cortisol production
Long bursts damage the hippocampus and diminish its ability to inhibit - therefore causing feedforward pathological loop
What is the major output nucleus of the hippocampus
Subiculum
What carries most of the axons of the output nucleus of the hippocampus?
The fornix
(the output nucelus of the hippocampus is the subiculum)
In the hippocampal circuit, which neurotransmitters are used?
ALL are glutamatergic, although GABAergic interneurons and cholinergic neurons modulate the circuitry
What is the function of the amygdala?
Involved in associative memory and emotion
Important in fear and reward conditioning
Which part of the limbic system plays an important role in associative memory?
Amygdala
Which part of the limbic system plays an important role in declarative memory?
Hippocampus
What is Kluver-Bucy Syndrome?
Bilateral lesions of the amygdala induce placidity, loss of fear, hypersexuality and hyperphagia
What type of lesion can induce placidty, loss of fear, hypersexuality and hyperphagia?
Bilateral lesions of the amygdala
Kluver-Bucy Syndrome
What are major foci of epilepsy?
Amygdala and Hippocampus
What is the funciton of the prefrontal cortex?
Working memory (keeping things “in mind”)
Executive function
Cognition
What is the function of the nucleus accumbens?
Major reward region of the brain
Pleasure, laughter, addiction, aggression, fear and placebo effect
What is the function of the septal nuclei?
Important in reward
Provides strong cholinergic innervations of hippocampus, which is crucial for cognition
What is the function of the bed nucleus of the stria terminalis?
Major output of the amygdala and innervates hypothalamus, septal nuclei and thalamus
Implicated in anxiety
What brain structure is implicated in anxiety?
Bed nucleus of the stria terminalis
What is the function of the lateral habenula?
Forms important interconnections with most limbic structures
What is the molecular basis for long-term memory?
Requires gene expression changes
Accompanied by plasticity (LTP & LTD) and changes in spines
What is declarative memory?
Explicit
Semantic and episodic
Characterized by exquisite temporal features
Hippocampus + Amygdala
What is procedural memory?
implicit memory
Habit or motor memory
Involves Striatum (caudate-putamen)
What type of memory is associated with the hippocampus and amygdala?
Declarative
What type of memory is associated with the striatum (caudate putamen)?
Procedural
What type of memory is associated with the prefrontal cortex?
Working memory
What is emotional memory?
Memories with strong emotional meaning that are strong and long lived
Mediated by monoamine systems (DA from VTA; NE from locus ceruleus; 5-HT from dorsal raphe)
Orexin too
What type of memory is mediated by the monoamine systems (DA, NE, 5-HT)?
Emotional memory
What part of the limbic system is important for emotions and drives?
Amygdala
What part of the limbic system is important for memory?
Hippocampus
What part of the limbic system is important for homeostasis?
Hypothalamus
What is the dorsolateral PFC involved in?
Important in executive function, working memory, decision making….
What is the anterior cingulate cortex involved in?
Reward, anticipation, empathy, emotional processing, motivation
What is the orbitofrontal cortex involved in?
Corrects and inhibits maladaptive emotional responses, mediates socially appropriate behavior
What part of the prefrontal cortex is important in executive function, working memory, decision making, etc?
Dorsolateral PFC
What part of the PFC is important in mediating reward, anticipation, empathy, emotional processing, and motivation?
Anterior cingulate cortex
Which part of the PFC is important in correcting and inhibiting maladaptive emotional responses, mediating socially acceptable behavior?
Orbitofrontal cortex
Which psychiatric disorders are associated with lymbic dysfunction?
Psychosis
Fear/Anxiety
Drives/Reward/Addiction
Sociopathy
What is the believed role of dopamien in schizophrenia?
Hyperactivity of dopamine neurons in the mesolimbic pathway may mediate positive symptoms of psychosis
Hypoactivity of dopaminergic neruons in mesocortical pathway may mediate negative acnd cognitive symptoms
What neurons mediate the positive symptoms of psychosis in schizophrenia?
Hyperactive dopaminergic neurons of the mesolimbic pathway
What neurons mediate the negative and cognitive symptoms of schizophrenia?
Hypoactivity of dopaminergic neurons in the mesocortical pathway
What is the neurophysiologic basis of cognitive dysfunction and disorganization in schizophrenia?
Decreased activity of dorsolateral PFC and dorsal anterior cingulate
Decreased hippocampal activity
What is the neurophysiologic basis of emotional dysregulation in schizophrenia?
Inability to engage amygdala, anterior cingulate and hippocampus in processing emotional stimuli
Dysfunctional interconnectivity b/w frontal and temporal regions
What is learning?
The strengthening of existing responses/behaviors or formation of new ones to existing stimuli taht occurs because of practice or repetition
What is habituation?
Repeated stimulation results in a decreased response (tuning things out)
What is sensitization?
Repeated stimulation results in increased response
What is classical conditioning?
The association of a neutral stimulus with an unconditioned stimulus, such that the neutral stimulus comes to bring about a response similar to that originally elicited by the unconditioned stimulus
What is the unconditioned stimulus?
A stimulus that, without training, automatically produces reflexive, unlearned response
What is the unconditioned response?
Response that occurs spontaneously to the unconditioned stimulus
What is the conditioned stimulus?
A neutral stimulus that elicits a conditioned response following learning
What is the conditioned response?
Behavior that is learned by an association made between conditioned stimulus and unconditioned stimulus. The response elicited by the conditioned stimulus
What is acquisition, with respect to classical conditioning?
Conditioned response is acquired or learned
What is extinction, with respect to classical conditioning?
Reduction of frequency of a learned response as a result of the cessation of reinforcement
What is spontaneous recovery, with respect to classical conditioning?
The increase in strength of an extinguished behavior after the passage of a period of time
What is stimulus regeneration, with respect to classical conditioning?
Conditioned response as a result of a new stimulus that resembles a conditioned stimulus
What is learned helplessnes?
Association (by classical conditioning) between aversive stimulus and the inability to escape
leads to hopelessness and apathetic response during subsequent exposures
What is imprinting?
Learning occuring at a particular age or life stage that is rapid and independent of the consequences of the behavior
What is operant conditioning?
Trial-and-error learning
Learning occurs because of the consequences to the individual of a previous behavior
Consequence determines whether behavior continues or not.
What is positive reinforcement?
Introduction of stimulus that results in an increase of the rate of a behavior
What is negative reinforcement?
Removal of an aversive stimulus that results in an increase in the rate of behavior
What are three types of fixed schedules of reinforcement?
Continuous - each time
Fixed ratio - reward given after set number of responses
Fixed interval - reward given after fixed amount of time
Describe the rate of learning and extinction in fixed schedules of reinforcement?
Rapid learning and rapid extinction
Describe the rate of learning and of extinction when you use variable schedules of reinforcement?
Slower learning, and more resistant to extinction
Which schedule of reinforcement is more resistant to extinction?
Variable
What are variable schedules of reinforcement?
Variable ratio - reward given after random and unpredectable number of responses
Variable interval - reward given at random and unpredictable amount of time
What neurons are activated after conditioned stimulus or primary reward is introduced? What neurotransmitter is used?
Nucleus basalis
ACh
What neurotransmitter plays a role in both positive reinforcement learning and aversive learning?
Dopamine
What brain regions do all drugs of abuse activate that triggers the reward pathways?
Mesolimbic dopamien system
Also increase dopamine levels in nucleus accumbens and elsewhere
What is Urbach-Wiethe disease?
Rare autosomal recessive disease
Bilateral calcification of anterior medial temporal lobes, especially amygdala
Cannot properly rate intensity of emotion or recognzie fearful stimuli
What is sociopathy/antisocial personality disorder?
lack of respect for social norms, obligations, and irresponsibility
Reckless, irritable, impulsive, aggressive behavior
Lack of remorse/guilt, empathy, compassion, fear
Repeated lying/conning
Onset before 15 yo
What limbic structures are associated with sociopathy?
Hypoactiviyt of the amygdala and orbitofrontal cortex
Ventromedial prefrontal cortex dysfunction
What is limbic encephalitis?
Autoimmune disorders that affect limbic system
Cardinal sign is subacute onset of short term memory loss
can have behavioral, psychiatric, confusion, seizures, or other neurological symptoms
What is subacute onset of short term memory loss a cardinal sign of?
Limbic encephalitis
What is the etiology of limbic encephalitis?
Autoimmune - associated with antibodies against intracellular antigens or neuronal surface antigens
Also may or may not be associated with neoplasms
What is the treatment for limbic encephalitis?
Immunotherapy, tumor removal and screening
What are the three major groups of limbic encephalitis?
LE associated with classical intracellular neuronal antigen antibodies - associated with neoplasm
LE associated with antibodies against neuronal surface antigens (+/- neoplasm)
LE associated with no known antibody (many associated with neoplasm)
What may you find in the CSF of a patient with limbic encephalitis?
Anti-neuronal antibodies, elevated lymphocytes and proteins, oligoclonal bands
Not always though
What strain of HSV typically causes Herpes simplex encephalitis?
HSV-1
how do you treat herpes simplex encephaitis?
Acyclovir
What are clinical features of medial temporal lobe dysfunction?
Impaired memory
Inabilty to judge emotional intensity
Inability to recognize fear
Dysregulation of fear
Altered sexuality
Mood changes
Normal intelligence
What is temporal lobe epilepsy?
Recurrent epileptic seizures from temporal lobes
Hallucinations, illusions, deja vu, out of body sensations, amnesia, mood chagnes, fear, anger, unusual behaviors
Hyper-religiosity ,circumstantiality, hypermorality, intensified mental life, altered sexuality, hypergraphia
What type of brain dysfunction is associated with hyper-religiosity, hyper-morality, intensified mental life, altered sexuality, and hypergraphia?
Temporal lobe seizures
What defines a seizure?
Release of excessive and uncontrolled electrical activity in the brain
What defines epilepsy (vs seizure)?
Neurological condition that in different times produces brief disturbances of the electrical functions of the brain
Epilepsy is 2 or more unprovoked seizures
What age demographics does epilepsy usually present in?
Childhood and the elderly
What is the major cause of seizures in children?
Developmental and infections
What is the major cause of seizures in the elderly?
Stroke
What are the two main categories of epilepsy?
Primary (idiopathic) generalized epilepsy - genetic; entire brain at once
Localization-related (Focal/Partial) epilepsy - specific part of brain
What type of seizure starts with the whole brain at once?
Primary (idiopathic) generalized epilepsy
What type of epilepsy starts in a specific part of the brain?
Localization-related (Focal/Partial) epilepsy
What type of epilepsy is caused by visual cues, mental actions (thinking), stimuli such as reading, writing, etc?
Reflex epilepsy
What is the main concern of a physician when evaluating an epileptic patient?
That it may be symptomatic of a treatable cerebral lesion
What is the frequency of delta waves and when are they found?
<4Hz - sleep
What is the frequency of theta waves?
4-8 Hz
What is the frequency of alpha waves and when are they found?
8-13 Hz; found in an awake, relaxed state
What is the frequency of beta waves?
>13 Hz
Increased in people on benzos and barbituates B!!!
What type of seizures are epilepsy auras indicative of?
Focal
Characterized by sudden intense fear, deja vu, olfactory hallucinations, rising abdominal sensation
A patient is experiencing intense fear, deja vu, olfactory and gustatory hallucinations, and rising abdominal sensation, what do you think might happen to him/her?
Epilepsy
These are classic aura symptoms
Do generalized tonic-clonic seizures have auras?
No!
Is there loss of consciousness in generalized tonic-clonic seizures?
Yes
May last 2-3 minutes, characterised by amnesia for the event
How long do generalized tonic-clonic seizures last?
2-3 minutes, followd by post-ictal period of confusion
What is happening here?
Generalized tonic-clonic seizure
What are some things you see in a seizure that involves the motor cortex?
Rhythmic movements of contralateral limb
What are some things you see in patients with seizures in their visual cortex?
Complex figures or colors in part of the visual field
What are absence seizures??
Sudden behavioral arrest characterized by staring, unresponsiveness, eye-blinking at 3Hz
Mostly young children
A young child is staring off into space and blinking at ~3Hz. What do you think?
Absence seizures
What are myoclonic seizures?
Brief, lightning-like whole body or portion seizures, often without loss of consciousness
A patient is jerking with brief, lightning-like motions, without loss of consciousness. What do you think?
Myoclonic seizure
What is juvenile myoclonic epilepsy?
5-10% of all epilepsies
Usually present with family history of epilepsy, with myoclonis early in the day (drops things in the mornings)
Requires anti-epileptic tx for life
What is mesial temporal sclerosis?
Hippocampal sclerosis causing temporal lobe epilepsy
Important cause of refractory complex partial epilepsy
Neuronal loss in CA1, CA3, CA4
Aura of risign epigastric sensation, intense fear, impaired consciousness and automatisms
Patient presents with aura of rising epigastric sensation, intense fear, impaired consciousness, and lip-smacking, chewing, and button picking. What are you thinking?
Mesial Temporal Sclerosis
Where do most focal seizures begin?
Temporal lobe
What auras are common in temporal lobe seizures?
Epigastric rising feeling, intense fear, deja vu, olfactory hallucinations
What are automatisms?
Lip-smacking, cheiwng, button picking often seen in patients having seizures
What is the second most common focal seizure?
Frontal lobe seizures (temporal is first)
What seizures can be bilateral without loss of awareness?
Frontal lobe seizures (only ones)
Which seizures feature a jacksonian march?
Frontal lobe seizures (myoclonus begins in one part of the body and migrates along the pattern of the motor homunculus)
What is a Jacksonian March?
myoclonus begins in one part of the body and migrates along the pattern of the motor homunculus
What are features of occipital lobe seizures/
Poorly formed colors with lights
May see stereotyped, complex forms
A patient has a seizure featuring poorly formed colors with lights, and sees complex, stereotyped forms. What are you thinking?
Occipital lobe seizure
What is Todd’s Paralysis?
Post-ictal condition of focal weakness in one part of the body. Helps discriminate between primary and secondary generalized seizures, because region of weakness will correspond to the epileptic foci
If localized = secondary
If diffuse = primary
What are Rolandic seizures?
Unilateral parasthesia (tingling) and clonus of the tongue, lip, pharynx
Often see dysarthria, drooling
Commonly undiagnosed and occur shortly after falling asleep
Resolve by adolescence
Young patient presents with tingling and drooling of mouth with impaired speech shortly after falling asleep. What are you thinking?
Rolandic seizures
What are Lennox-Gaustat seizures?
Triad of mental retardation, slow spike and wave, and multiple seizures
Generally less than 8 years old
Tonic seizures out of sleep
Tx is difficult
What is the difference between tonic vs clonic seizures?
Tonic = tighten up and lose consciousness
Clonic = spasmic, no loss of consciousness
What are febrile seizures?
Benign seizures accompanying fever in children 3 months - 5 years old
Where do brain tumors occur that are generally not associated with seizures?
Cerebellum and brainstem
When should withdrawal of pharmacotherapy be considered in an epileptic patient?
When a patient is seizure-free for three years - must weigh benefits with potential for seizures and the impact it could have on employment, etc
What is status epilepticus??
Seizure lasts more than 30 minutes or multiple seizures lasting 30 minutes without recovery in between
May be life-threatening
What do the chemical structures of drugs of abuse all have in common?
NOTHING!
What defines drug addiction?
Loss of control over drug use
Compulsive drug seeking and taking despite horrendous adverse consequences
What tolerance, with regards to drug use?
Reduced drug effect after repeated use
What is sensitization with respet to drug use?
Increased drug effect after repeated use (opposite of tolerance)
What is dependence, with respect to drug use?
Altered physiological state that leads to withdrawal symptoms upon cessation of use
How can you know if a patient is dependent on drugs?
If they experience withdrawal symptoms upon cessation
What causes drug addiction??
Drug-induced changes in reward or reinforcement of drug use
Includes tolerance, sensitization, or dependence in reward-reinforcement mechanisms
What is reinforcement?
A stimulus that causes a response to be maintained and increased
What are examples of positive reinforcement?
Food, sex, etc
What are examples of negative reinforcement?
Pain, starvation, etc
What neurons in the brain are the “rheostats” of reward?
VTA dopaminergic neurons
What is the function of the VTA dopaminergic neurons?
They are the “rheostats” of reward
Activated by rewards, expectations of rewards
Absence of expected reward inhibit these neurons
Hyperactivated by unexpected rewards
What brain region is activated by rewards? What is the effect of an unexpected reward?
VTA dopaminergic neurons
Unexpected rewards activate it even more
What is the difference between drugs of abuse and natural rewards?
Drugs of abuse activate the same regions better (VTA dopaminergic neurons)
What is the mesolimbic pathway?
VTA to Nucleus Accumbens pathway that is very important in reward
The NAc can influence behavioral by virtue of its connection with the ventral pallidum (basal ganglia).
What is the mesocorticolimbic pathway?
The meso-corticolimbic pathway enables integration of information about the reward, retrieval of internal motivational states for action planning, learning about the reward, and focusing of attention on the reward and the context in which it is being given
What are long-lasting changes in the brain that occur in addiction?
Reduced resopnses to natural rewards
Sensitization of responses to drugs of abuse and associated cues
Impaired cortical control over more primitive reward pathways
What are cortical changes seen in addiction (e.g. cocaine abusers)
Hypofrontality
What drugs block the dopamine pump?
Cocaine - blocks it
Amphetamine - reverses it
What drug reverses the action of the monoamine transporter?
Amphetamine
Where do opiates act?
All are agonists or partial agonists at the μ opioid receptor
What is the difference between opiates (e.g. morphine and heroin, or methadone, oxycontin, buprenorphine)?
Pharmacokinetics - all have similar activity
What does the activity of opiates mimic?
Endogenous opioid peptides (enkephalins, endorphins, dynorphins)
What are opioid receptor antagonists?
naloxone, naltrexone
How do you treat opiate overdoses?
Naloxone, naltrexone
What are the effects of opiates?
Analgesia, euphoria, sedation, constipation, respiratory depression
Can cause profound dependence, and tolerance, but are addictive
Where do stimulants act?
On monoamine systems - their action depends on monoamine transporters (cocaine, amphetamine, …)
What is the net effect of stimulant use?
Increase monoaminergic transmission (bocking pump, reversing pump, etc)
What are the effects of stimulants?
Euphoria, increased arousal, suppression of fatigue, increased confidence, appetite suppression
What action of stimulants deveops tolerance?
Euphoria, tachycardia
What action of stimulants experiences sensitization?
Activation, paranoia, psychosis, irritability
What are the actions of nicotine?
Causes increased alertness, muscle relaxation, analgesia, nausea, psychomotor activation
What is the action of PCP and ketamine?
Non-competitive NMDA glutamate receptor antagonists
What addictive drugs are NMDA glutamate receptor antagonists?
PCP, ketamine
Under what circumstances does alcohol have effects in the brain?
At very high concentrations
What explains alcohol’s complex and concentration dependent effects? (Anxiolytic<< dissociative, psychotogenic << coma, death)
It’s effects on transmembrane proteins (receptors/channels)
GABA-A << NMDA << voltage-gated chanels
What is the mechanism of opiate tolerance and dependence?
Upregulation of the cAMP-CREB pathway
What is the importance of upregulated cAMP-CREB pathway proteins?
Common adaptation to drug exposure seen in many brain locations that explains the long-term effects of opiates
What are treatment avenues for drug addiction?
Replacement therapy (with partial agonists or longer-acting agonists)
Antagonist therapy (e.g. naltrexone/naloxone) - less efficacious
Antidepressants - only in depressed patients
Behavioral therapies
What are functions of the hypothalamus?
Regulates:
Homeostasis
Body Temp
Hunger, thrist, metabolism
Emotional states
Circadian rhythms
Sleep/wakefulness
Reproductive functions
How does the hypothalamus exert its broad regulatory effects?
Neuroendocrine control of the pituitary gland
ANS control
Diverse projections to various other brain and spinal cord regions
Identify teh paraventricular nucleus
Identify the supraoptic nuclei
What key feature of the CNS is not well developed in the hypothalamus?
The Blood-Brain barrier
What is the function of the preoptic area and anterior hypothalamus?
Thermoregulation - cytokines acting here cause fever by activating prostaglandin synthesis here
Regulation of fluid and electrolyte balance
Regulation of sexual behavior
Ventrolateral preoptic area is crucial for sleep
What causes fever?
Peripheral cytokines acting on the preoptic area and anterior hypothalamus, activating prostaglandin synthesis
What is the ventrolateral preoptic area crucial for?
Sleep
What is the function of the suprachiasmatic nucleus?
Master circadian clock that entrains with environmental light
Where is the site of the master circadian clock that entrains with environmental light?
Suprachiasmatic nucleus
What is the function of the arcuate nucleus (a.k.a. infundibulum)
Regulation of feeding and body weight (Neuropeptide Y, agouti-related peptide, and melanocortin)
Neuroendocrine regulation via anterior pituitary (dopaminergic regulation of prolactin, GHRH regulates growth hormone)
What is another name for the arcuate nucleus?
Infundibulum
What is the infundibulum?
Arcuate nucleus
What is the function of the ventromedial nucleus?
Regulates feeding, drinking and body weight (reduces)
Thermoregulation via CNS projections
Sexual behavior
What is the function of the dorsomedial nucleus?
Regulation of feeding, drinking and body weight (reduces)
What is the function of the lateral hypothalamus?
Regulation of feeding and body weight (increases)
Regulation fo seep-wakefulness
What is the function of of the magnocellular neurons in the paraventricular nucleus?
Make oxytocin and vasopressin (ADH)
Project directly to posterior pituitary
Which paraventricular nuclei cells make oxytocin and vasopressin, projecting to the posterior pituitary?
Magnocellular
What is the function of the parvocellular paraventricular nuclei cells?
Make “releasing factors” that go directly to the anterior pituitary
CRH - corticotropin
TRH - thyrotropin
GnRH - gonadotropin
Which paraventricular nucleus cells make the “releasing factors”
Parvocellular
What is the difference between the magno and parvo cellular paraventricular nucleus cells?
Magno - posterior pituitary - oxytocin/vasopressin
Parvo - anterior pituitary - releasing factor
What do magnocellular cells of the hypothalamus make?
Vasopressin - project direclty to hte posterior pituitary
(paraventricular nuclei cells aso make oxytocin; supraoptic nucleus cells only make vasopressin)
What is the function of the paraventricular nucleus?
Magnocellular neurons - oxytocin + vasopressin to posterior pituitary
Parvocellular neurons - releasing factors to anterior pituitary (CRH, TRH, GnRH)
What is the function of the supraoptic nucleus?
Magnocellular neurons make vasopressin, and project to the posterior pituitary
Where do parvocellular cells of the paraventricular nucleus project to?
Anterior pituitary
Where do magnocellular cells of the paraventricular nucleus project to?
Posterior pituitary
What is the function of the mammillary nuclei?
Important in memory - including olfactory memories
Fornix is the major output of the hippocampus
Which brain region is important in memory, particularly olfactory memories?
Mammillary nuclei
What is the function of the tuberomammillary nucleus?
Only source of histamine in the brain
What is the only source of histamine in the brain?
Tuberomammillary nucleus
What are the inputs to the HPA axis?
Hippocampus (negative)
Amygdala (positive)
To parvocellular cells of the paraventricular nucleus - release releasing factors
How does the hypothalamus control the ANS?
Reciprocal connections
Inputs from the nucleus of the solitary tract and the reticular formation
Outputs to medulla (parasympathetic vagal nuclei; preganglionic sympathetics in IML nuclei of spinal cord) from hypothalamus
What are the inputs to the hypothalamus important in controlling the ANS?
Nucleus of the solitary tract
Reticular formation
What are the outputs of the hypothalamus important in controlling ANS?
To medulla including parasympathetic vagal nuclei, preganglionic sympathetic neurons in the IML nuclei of the spinal cord
What nucleus is critical to entrain circadian rhythms in the body to environmental light?
The suprachiasmatic nucleus (SCN)
Innervated by optic nerve directly and indirectly
SCN innervates superior vervical sympathetic ganglia which innervate the pineal gland - releases melatonin
Is melatonin released during light or dark?
Dark only
How is melatonin release achieved?
Information about light travels via the optic nerve and then directly and indirectly activates the suprachiasmatic nucleus.
This innervates the superior cervical sympathetic ganglion, which in turn innervates the pineal gland.
Pineal gland releases melatonin when not inhibited (norepinephrine inhibits pineal gland)
Light results in inactivation of pineal gland and no melatonin release
What is the molecular clock of the circadian rhythms?
Clock/Period/Bmal is the molecular circadian clock found in all cells in the body
Functional endpoint of the suprachiasmatic nucleus cells regulation
This clock will function autonomously even in the absence of SCN entrainment
How does hte molecular clock work?
Clock/Bmal continuously degrades Period/cry and vice versa
How do organs differ with respect to their circadian rhythms?
Specific tissues are differentially sensitive to the regulation of the molecular clock by the suprachiasmatic nuclei
What is orexin/hypocretin?
Expressed solely in lateral hypothalamus
Promotes wakefulness, arousal, and reward; this produces pro-feeding effects
What neurotransmitter produces pro-feeding effects and is important in wakefulness, arousal and reward?
Orexin
What is narcolepsy?
Sleep disorder that features abnormal switches between REM and non-REM sleep, featuring intrusive periods of REM sleep during awake periods
Normal amount of sleep per 24 hours
What is the role of orexin in narcolepsy?
Orexin knockouts are narcolepsy-like
Narcolepsy is associated with a loss of orexin neurons in the hypothalamus
How is temperature associated with sleep/wakefulness/REM/NREM sleep?
Cool during sleep
Warm during wakefulness
Warming induces NREM sleep
How is BMI calculated?
weight (kg)/ (height in m)^2
What is anorexia nervosa?
Syndrome of self-starvation seen much more commonly in females
Body weight 15%+ below normal
Intense fear of being fat
Grossly distorted body image
Often accompanied by amenorrhea
10% mortality
Is anorexia nervosa fatal?
10% mortality
What is bulimia?
Syndrome of binge eating and purging, seen much more commonly in females
Requires recurrent episodes of binge eating (loss of control), with regular purging; persistent over-concern with body weight
Body weight can be normal, high or low
Can be fatal (electrolyte abnormalities)
What percentage of the risk for obesity can be attributed to genetic factors?
70% !!!
What parts of the brain are pro-appetite (orexigenic)?
Lateral hypothalamus
Lesions cause starvation
What parts of the brain are anti-appetite (anorexigenic)?
Medial hypothalamus
Lesions cause hyperphagia and obesity
What would be the result of a lesion to the lateral hypothalamus?
Starvation
What would be the result of a lesion to the medial hypothalamus?
Hyperphagia and obesity
What role does the hypothalamus play in feeding behavior?
Physiological need for food (hunger)
What role does the mesolimbic dopamine system play in feeding behavior?
Desire for food as a rewarding substance
(appetite)
What role does the cerebral cortex play in feeding behavior?
Control over behavior - integration with psychological and social factors
(top-down control)
What is the lipostat model of weight control?
Adipocytes produce leptin in response to weight gain (leptin levels are a relative marker of body adiposity)
Leptin then promotes anorexigenic factors and inhibits orexigenic factors in order to reduce food intake, increase energy use, and increase sympathetic tone
This works backwards in response to weight loss
What is leptin?
Peptide synthesized in adipocytes that is made proportionally to the volume of fat
Acts on hypothalamus to decrease feeding, increase energy utilization, and decrease energy storage
What are the targets for leptin?
Arcuate nucleus of the hypothalamus
Inhibits orexigenic factors (NPY, agouti-related peptdie)
Stimulates anorexigenic factors (α-MSH, aka melanocortin; CART, a.k.a. cocaine- and amphetamine-regulated transcript)
How do we go from leptin to body-wide effects?
Leptin acts on the arcuate nucleus of the hypothalamus, causing neuropeptide Y and agouti-related protein (orexigenic) and melanocortin and CART (anorexigenic) to be released
These act in the lateral and medial hypothalamus to regulate further anorexigenic factors (CRH, TRH - medial) and orexigenic (Melanin concentrating hormone - lateral)
Are neuropeptide Y and agouti-related protein anorexigenic or orexigenic?
Orexigenic
What is neuropeptide Y?
Most prevalent neuropeptide in the brain
Powerfully orexigenic (most powerful)
Gi linked receptor function
Act on medial hypothalamus (paraventricular nucleus), inhibiting anorexigenic peptides; and on lateral hypothalamus where they stimulate orexigenic peptides
What is melanocortin?
Derived from POMC
Expressed in pituitary and in arcuate nucleus
Gs linked
Are anorexigenic peptides generally Gs or Gi linked?
Gs
Are orexigenic peptides usually Gs or Gi linked?
Gi
What is the receptor for melanocortin?
MC4 receptor (Gs linked)
Agouti-related peptide is a natural antagonist (orexigenic)
What is melanin-concentrating hormone?
Expressed in lateral hypothalamus
Major orexigenic peptide (knockouts are lean)
Actions via MCH receptors (Gi linked)
Are CRF and TRF orexigenic or anorexigenic?
anorexigenic
Is CART orexigenic or anorexigenic?
Anorexigenic
cocaine- and amphetamien-regulated transcript
What other peptides (aside from leptin) regulate feeding and satiety?
Insulin, glucose
What is ghrelin?
Peptide secreated by stomach as a function of fasting (more fasting = more ghrelin)
Strongly orexigenic
When is bariatric surgery recommended?
Only for extreme cases of obesity
Are amphetamines appetite suppressants or appetite enhancers?
suppressors
What is the function of agents that enhance serotonin (i.e. SSRIs) with respect to eating?
Appetite suppressants
Are cannabinoids appetite suppressants or enhancers?
Enhancers
CB1 receptor activation stimulates appetitie
What are medical complications of eating disorders?
Gastric reflux, ulcers, dehydration, cardiac arrhtyhmia, constipation, osteoporosis, dental erosion
What is the distinguishing feature of anorexia (with purging) vs bulimia?
Low weight!
What is binge eating disorder?
Recurrent binges (eating larger amount of food than others in period of 2 hours; sense of lack of control)
Associated with eating more rapidly; uncomfortably full; eating when not hungry; eating alone; feeling disgusted with self
Not associated with inappropriate compensatory behaviors
What objectively defines a binge?
Eating an abnormally large amount of food - 3 meals’ worth
What behaviors do individuals with eating disorders exhibit?
Establishment of rigid rules or exercise rituals
Restricting diet , etc
Breaking rules leads to further restrictions
What is the critical period for the development of anorexia nervosa?
Adolesence - has gonadal hormones that affect developing brain. Highly sensitive
What proportion of individuals recover rom anorexia nervosa?
30%
Which has a higher incidence in men, anorexia nervosa or bulimia nervosa?
Bulimia (only 5:1); Anorexia is 10:1
What personality traits do anorexic individuals typically exhibit?
Obsessive, preservative and rigid personality styles with difficulty shifting attention
Do well with goal-directed behavior; Do poorly with incorporating feedback and modifying behviors
What do neurophysiological models suggest for the basis of anorexia nervosa?
Sensitivity of 5-HT system
Neuroendocrine system may fail to adapt back to normal weight during critical window of adaptation (adolescence)
What is the role of 5-HT in bulimia?
Predisposition of 5HT dysregulation can be implicated
Difficulty regulating the internal drive to eat -> binge
What defines sleep?
Normal reversible recurring behavioral state of disengagement and unresponsiveness to the environment that is characterized by typical changes in the EEG
What is the function of sleep?
Ecological/environmental advantage
Physical restoration
Optimization of waking neurocognitive and emotional function
Learning, emotional processing
Health and survival
What are the stages of sleep?
Waking - alpha waves (8-12 Hz)
Stage 1 - light sleep w/ theta waves (4-7 Hz)
Stage 2 - theta waves w/ sleep spindles and K complexes
Stage 3 & 4 - Deep sleep w/ delta waves (0.5-2 Hz)
Which sleep stage do you see sleep spindles and k complexes?
Stage 2 of NREM sleep
What happens to HR during REM sleep?
Increases
What is the sleep cycle?
What is sleep latency?
Time from “lights out” to the first NREM stage 1 (usually 10-20 minutes)
What is REM latency?
Time from sleep onset to ferst REM (usually 90-100 minutes)
Narcolepsy goes right to REM
What is sleep efficiency?
Amount of sleep/amount of time in bed X 100
What is a typical time for sleep latency?
10-20 minutes
What is a typical amount of time for REM latency?
90-100 minutes
How do sleep patterns change with age?
Infants sleep 2/3 of day; 50% REM
Adults sleep 1/3 of day; less REM
What changes do we see in sleep with aging?
Increased sleep latency, awakenings, NREM stage 1
Decreased Delta sleep, REM sleep, REM latency, efficiency
What are dyssomnias?
Too little or too much sleep
What are parasomnias?
Abnormal behaviors or physiologic events that arise during specific sleep stages or during transitions between wakefulness and sleep
What are the primary sleep disorders?
Dyssomnias and parasomnias
What is sleep apnea?
Repetitive episodes of complete or partial cessation of air flow during sleep that often results in oxygen desaturation and terminates with brief arousals
Can be result of reduction of respiratory drive or obstruction
What is central sleep apnea?
Results from reduction of respiratory drive
What is obstructive sleep apnea?
Resulting from upper airway obstruction
How long must airflow be stopped for it to qualify as apnea?
>10 seconds
What is hypopnea?
Reduction of airflow for > 10 seconds
What is a respiratory event-related arousal?
Reduction in ariflow for < 10 seconds that results in arousal
What is the apnea-hypopnea index (AHI)?
Number of apneas and hypopneas per hour
What are signs and symptoms of obstructive sleep apnea?
Excessive daytime sleepiness unexplained by other factors
Also associated with loud, disruptive snoring; choking/gasping while sleeping; pauses in breathing while sleeping
What are the consequences of obstructive sleep apnea?
increase in all-cause mortality (3-6x)
CHF (right sided), stroke, HTN
Increased car accidents
Decreased vigilence, executive functioning, coordination
Which demographics are more likely to get obstructive sleep apnea?
Increasing incidence with age up until 55-65 years old
Males
Obesity is big risk factor
What are therapies for obstructive sleep apnea/
Weight loss
Positional therapy
Surgery
CPAP masks (positive airway pressure)
Exercises
Avoiding alcohol, sedatives
What is different in central sleep apnea from obstructive sleep apnea?
There is no respiratory effort during apneic periods
Seen in patients with lower brainstem lesions
What is the classic tetrad of narcolepsy?
Excessive daytime somnolence, cataplexy, sleep paralysis, and hypnagogic or hypnopompic hallucinatoins
What is sleep paralysis?
Inability to move when falling asleep or upon awakening
What are hypnagogic/hypnopompic hallucinations?
Vivid hallucinations during transitoin between wakefulness and sleep
What is cataplexy?
Sudden intrusions of REM sleep into wakefulness, resulting in emotionally-triggered transient muscle weakness
Who gets narcolepsy?
Male = Female
Usually in teens, but may occur <10 or >50
What is the pathophysiological basis for narcolepsy?
Dysfunction of the hypothalamic neuropeptide orexin (hypocretin) - reduced levels
What is ondine’s curse?
Total loss of automatic breathing, especially during sleep
Apneic periods followed by awakenings
Caused by absent external arcuate nuclei of medulla and depleted neuronal population in medullary respiratiory areas
What is shift-work sleep disorder (SWSD)?
Excessive sleepiness during work hours that are scheduled during usual sleep period
Insomnia when trying to sleep during usual wake period
Commonly seen in night and early morning shift schedules
Decreased total sleep time, poor sleep quality
How do you treat SWSD?
(Shift-work sleep disorder)
Maintenence of regular and comperable sleep-wake schedule during work and non-work days
Exclude other causes
Some people can’t handle such schedules
Phototherapy (expose to light to combat somnolence)
Stimulants
What demographic gets NREM parasomnias more than REM parasomnias?
Children
Older men get REM parasomnias more than NREM parasomnias
What sleep stage are NREM parasomnias present in?
Delta sleep (NREM 3 or NREM 4)
What stage are REM parasomnias present in?
REM
Are patients with NREM sleep disorders dreaming?
NO
Are patients with REM parasomnias dreaming?
Yes!
What are REM parasomnias?
Nightmare disorder, REM behavior disorder
What are NREM parasomnias?
Sleepwalking disorder
Sleep terror disorder
Is sleep walking a REM parasomnia?
NO! NREM
What are LP findings in patients with acute bacterial meningitis?
Elevated opening pressure
Low glucose
Elevated protein
Elevated WBC
Elevated opening pressure on LP. Low glucose, high protein and high WBC. What are you thinking?
Acute bacterial meningitis
What are the most common causes of meningitis in adults?
S. pneumoniae
N. meningitidis - scariest
H. influenzae
What are the most common causes of meningitis in adults 60 yo or older?
S. pneumoniae
L. monocytogenes
What are the most common causes of meningitis in neonates?
Group B Strep
E. coli
Listeria monocytogenes
Other gram-negatives
Not N. meningitidis
What is a serious complication of acute bacterial meningitis?
Secondary vasculitis
Can cause infarcts
What are predisposing factors for meningococcal meningitis?
Close contact
Crowding (college dorms, barracks, etc)
How do you treat meningococcal meningitis?
Rifampin to those exposed
What is this petichial purpura rash indicative of?
Meningococcal septicemia
What is waterhouse-friderichsen Syndrome?
Bleeding into adrenal gland due to severe bacterial infection
Usually N. meningitidis
leads to adrenal failure and hypotension
How can you prevent bacterial meningitis?
Vaccination!
H. flu, N. meningitidis, S. pneumoniae are available
How do you treat bacterial meningitis?
Antibiotics immediately
3rd or 4th gen cephalosporin + ampicillin; PCN
HIV = add RIPE therapy
Meningococcal = Rifampin
Corticosteroids can help vasculitis
Must cross BBB
What signs would you see in a neonate with bacterial meningitis?
Signs may be absent
Can see bulging fontanelles due to elevated ICP
Caused by GBS, E. coli
In which patients would you expect to not see meningeal signs in bacterial meningitis?
Neonates
Alcoholics
Elderly
Immunosuppressed
In a patient with a subacute meningitis, what are you thinking?
Abscess
Atypical infection (syphilis, lyme, TB)
Fungus
Protozoa
parasite
What are the most common causes of viral meningitis?
Coxsackie B
Echovirus (enterovirus)
HIV
HSV-2
West Nile Virus (arbovirus)
What is seen in the CSF of a patient wtih viral meningitis?
Lymphocytes
Glucose and protein are normal / slightly decreased
What do abscesses mimic?
Brain tumors
focal neurological signs
40% don’t present with fever
Obtundation
Herniation
What do you see on LP in tuberculous meningitis?
Very high protein
Very low CSF glucose (extremes)
High WBC
What are the symptoms of neurosyphilis?
Cranial nerve lesions
Peresis with psychological symptoms
What do you see in the CSF of a neurosyphilis patient?
Positive CSF VDRL
Negative VDRL does not rule out
Negative CSF FTA rules out neurosyphilis
Positive CSF FTA doesn’t make diagnosis
What are the primary pathogens that cause fungal infections?
Cyrptococcus neoformans
Histoplasma capsulatum
Coccioides immitis
Paracoccidioides barziliensis
Blastomyces dermatitidis
Apsergillus, candida, mucorales (opportunistic)
When do you see cryptococcal meningitis?
AIDS patients or immunosuppressed
What do you see on CSF of cryptococcal meningitis?
Elevated OP
elevated WBCs
Low glucose
Elevated protein
Budding yeast
What is mucormycosis?
Most aggressive fungal infection
Seen in diabetics: ketoacidosis, not hyperglycemia
Spreads via cavernous sinu
What type of infection would you suspect in a patient with diabetes in ketoacidosis presenting with cavernous sinus thrombosis?
Mucormycosis
What would you suspect in a patient presenting with meningitis/neurological symptoms who had been swimming in warm ponds?
Naegleria fowleri
“Brain Eating Amoeba”
Directly spread from nasal cavity
What infectious agent is associated with transmission from domestic cats and other felines and can present with multiple ring enhancing lesions on CT?
Toxoplasmosis
What are causes of encephalitis?
Virauses
Enterovirus, HSV-1, arbovirus
Does HSV-1 or HSV-2 cause encephalitis?
HSV-1
Does HSV-1 or HSV-2 cause meningitis?
HSV-2
What are signs of herpes simplex encephalitis? What causes it?
Aphasia
Impaired memory
Temporal lobe sharp waves on EEG
Get PCR to confirm
Tx with acyclovir
HSV-1 causes encephalitis
What are localizing symptoms of brain tumors?
Aphasia
Weakness
Visual field cut
Seizures
Hemi-neglect
Gait disturbances
Incoordination
What are non-localizing sympoms of brain tumors?
Headache
N/V
Mental status changes
Caused by increased ICP
What is the location of most adult brain tumors?
Supratentorial
