week 2- neuro Flashcards
(93 cards)
1
Q
• BRAIN =
A
o Cerebrum, Cerebellum, Brain Stem
2
Q
• Cerebrum=
A
o 2 hemispheres: R & L
o 4 lobes: frontal, parietal, temporal, occipital
3
Q
• Frontal Lobe=
A
o principal speech area: Broca’s, motor component of speech
o primary motor area (precentral gyrus): motor homunculus (inverted human: HAL)
4
Q
• Parietal Lobe=
A
o primary sensory area (postcentral gyrus): sensory homunculus
o Major association areas located where lobes meet
5
Q
• Temporal and occipital lobes:
A
o T: auditory area, hearing, superior temporal gyrus; Language: Wernicke’s area: sensory component of speech
o O: vision: primary visual cortex
6
Q
• other subdivisions of cerebrum:
A
o gyri (bulges) o fissures (large indentations) o sulci (small indentations)
7
Q
• Cerebellum:
A
o 2 hemispheres, cortex of gray matter on surface, central masses of motor related nuclei, bands of white matter
o attached to brain stem by 3 cerebellar peduncles
o fxn: equilibrium and position sense (unconscious proprioception); fine movement; control of muscle tone; overall coordination of muscular activity for proprioception, descending traffic from higher centers
o Spinocerebellar tract: receives afferent info from periphery; Tracts come from same side and do not cross
8
Q
• Cerebellar Disorders:
A
o Ataxia: awkwardness of posture and gait
o ↓ tendon reflexes on affected side
o Asthenia: muscles tire easily
o Tremor: usu intention tremor (w purposeful movt)
o Nystagmus
9
Q
• Brain stem:
A
o 3 parts: Midbrain, Pons, Medulla
o Most CNs (except I, II) derived from brain stem (12 pair); 3 sensory, 5 motor, 4 mixed; (CNs actually considered part of PNS)
10
Q
• CNs:
A
o Olfactory (I); sensory; smells o Optic (II); sensory; sees o Oculomotor (III); motor; constricts pupil, accommodates o Trochlear (IV); motor; moves eyes o Trigeminal (V); mixed; chews and feels front of head o Abducens (VI); motor; moves eyes o Facial (VII); mixed; moves the face, tastes, salivates, cries o Vestibulocochlear (VIII); sensory; hears, regulates balance o Glossopharyngeal (IX); mixed; tastes, salivates, swallows, monitors carotid body and sinus o Vagus (X); mixed; tastes, swallows, lifts palate, talks, communication to and from thoraco-abdominal viscera o Spinal Accessory (XI); motor; turns head, lifts shoulder o Hypoglossal (XII) motor; moves tongue
11
Q
• Spinal cord:
A
o enters skull thru foramen magnum to become brain stem
o Central gray matter (neuronal cell bodies and synapses)
o Peripheral white matter (ascending and descending pathways)
o Ascending pathways: sensory info to brain
o Descending pathways: motor instructions down from brain
o Sites of contralateral crossing over of pathways within the white matter is important clinically
12
Q
• Tracts of spinal cord:
A
o Ascending (sensory): Pain-temperature, Proprioception: stereognosis, Light Touch o Descending (motor)
13
Q
• Ascending tracts:
A
o Spinothalamic, posterior columns, spinocerebellar
14
Q
• Spinothalamic Tract
A
o Pain-temperature, some light touch
o Crosses over to other side of spinal cord almost immediately → ascends to thalamus and cerebral cortex on that opposite side
o → a lesion in spinothalamic tract → loss of pain-temperature sensation contralaterally, below level of lesion
15
Q
• Posterior Columns:
A
o conscious Proprioception/stereognosis, vibration, and some light touch
o 2 columns: fasciculus gracilis, fasciculus cuneatus.
o Initially remains on same side of spinal cord. Crosses over at junction of spinal cord and brain stem
16
Q
• Spinocerebellar
A
o unconscious proprioception
o Does not cross spinal cord
o Ipsilateral sxs
17
Q
• Descending Tracts (Motor)
A
o =Corticospinal Pathway
o Extends from motor area of cerebral cortex down thru brain stem, crossing over at medial lemniscus (junction bw brain and spinal cord)
o Synapses in anterior horn (motor grey matter) of spinal cord just prior to leaving cord
o Upper Motor Neuron (UMN): pathway from brain to spinal cord before synapse
o Lower Motor Neuron (LMN): postsynaptic pathway from spinal cord to periphery (peripheral nerve)
18
Q
• Diencephalon
A
o = all the structures w “thalamus” = thalamus, hypothalamus, epithalamus, subthalamus
o Thalamus: Sensory relay and integrative center connects many areas of brain: cerebral cortex, basal ganglia, hypothalamus, brain stem; All sensory pathways synapse in thalamus, then relayed
o Hypothalamus: Contains a few nuclei w variety of functions; Produces hormones that control: body temp, hunger, moods, release of hormones from many glands: pituitary, sex drive, sleep, thirst
o Epithalamus: Main part is pineal gland
o Subthalamus
19
Q
• Basal ganglia
A
o Part of base of brain, 3 clusters of neurons (caudate nucleus, putamen, globus pallidus), responsible for involuntary movements: tremors, athetosis, chorea
20
Q
• Disorders of Basal Ganglia
A
o Parkinsonism: rigidity; slowness; resting tremor; mask-like facies; shuffling gait, assoc w degeneration in basal ganglia, substantia nigra
o Chorea: sudden, jerky, purposeless movements
o Athetosis: slow writhing, snake-like movements, esp. fingers and wrists
o Hemiballismus: sudden wild flail-like movt of one arm
21
Q
• Basic Functional Unit of CNS:
A
o neuron: Info travels down dendrite into neuronal cell body and axon; Information shared bw neurons thru synapses
o pathway= chain of communicating neurons. In CNS a bundle of pathway axons= a tract, fasciculus, peduncle, or lemniscus; Outside CNS (peripheral nerves, which connect CNS with skin, muscles, other organ systems) a bundle of pathway axons = nerves
22
Q
• Blood Supply to brain
A
o 2 main pairs of arteries supply brain
o 2 internal carotid: supply anterior cerebrum: become anterior cerebral a and middle cerebral a
o 2 vertebral arteries: supply posterior cerebrum (vertebral artery changes its name to → Basilar at level of Pons → Posterior Cerebral Artery at Cerebrum)
23
Q
• Meninges
A
o PAD surrounds entire CNS including spinal cord and optic nerve
o Pia mater: thin and vascular, closest to tbrain
o Arachnoid: avascular
o Dura: thick, double layer of CT contiguous w bone with thick venous channels. Dips down bw cerebral hemispheres as false cerebri, bw cerebrum and cerebellum as tentorium cerebelli
24
Q
• Sinuses
A
o Superior Sagittal Sinus: Spinal fluid drains here
o Cavernous Sinus: Drains eye; potential source into brain of infx from eye or face
o Transverse Sinus: Runs by ear: may become involved in inner ear infx
25
• CSF
o Clear colorless fluid secreted by choroid plexus into ventricles
26
• General Organization of PNS
o Spinal Nerves (31 pair)
o Somatic Nervous System: Voluntary control of body via skeletal muscles
o Autonomic or Visceral Nervous System: parasympathetic and sympathetic
27
• Parasympathetic Division
o Synapse very close to or within their end organs
o Anabolic system, conserving energy: Slows heart rate, promotes absorption and digestion of food
o CN 3,7, 9, 10 have parasympathetic components
o CN3: ciliary body of iris→ constriction
o CN7: lacrimal, submandibular, sublingual glands → tearing, salivation
o CN9: parotid → salivation
o CN10: many organs (lungs, heart, stomach, intestines)
28
• Sympathetic Division:
o Motor fibers synapse relatively near spinal cord
o catabolic system, expending energy: fight or flight response to danger
o ↑ HR and contractility of heart, shunting blood to muscles and heart
29
• Neurologic Approach to the Patient
```
o Stepwise Approach:
o Where is the lesion?
o What is the lesion?
o Identify pathophysiology
o Generate DDx
o Select specific tests
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30
• Where is the lesion?
o Location of the lesion(s) causing sxs
o One lesion or multifocal? Multifocal implies metastatic dz, MS, presence of 2 different dzs, malingering, hysteria
o Confined to nervous system or part of systemic do?
o What part of nervous system is affected? Peripheral nerves, spinal cord, brainstem, higher
31
• What is the lesion?
o Tumor, Infection, Hemorrhage?
32
• History
o Essential in order to localize sxs
o May need family member/support person to help corroborate hx
o PHx, FHx, Meds, allergies, environmental exposures, SHx, ROS
33
• PHx
```
o Cardio- HTN? CVD?
o Neuro- Stroke? TIAs? Psychiatric illness?
o Endocrine- DM?
o Hepatobiliary- Liver dz?
o Trauma- TBI? Concussions? MVAs?
o Overall Systemic- CA hx?
```
34
• FHx, SHx
o F: Hx of AD? PD? CVD?
o S: Smoking? ETOH? Drugs? Sexual hx (risk for neurosyphilis?); Diet (gluten?); Hobbies (exposure to heavy metals, solvents)
35
• ROS
o Pain? HEENT- Headache? Visual changes? Dizziness
| o Neuro- Tremor? Weakness or sensory loss? LOC? Motor dysfunction. Speech or swallowing concern
36
• Exams:
```
o MSE
o CNs
o Motor system
o Coordination, stance, gait
o Sensory testing
o Reflex testing
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37
• MSE:
o FOGS; Mini Mental Status Exam (MMSE) or Montreal Cognitive Assessment (MoCA)
o Family Story of Memory Loss
o Orientation: To precise time (month, day, year)
o General Information: e.g. Who are president and vice president of the U.S.?
o Spelling: spell “WORLD” forwards and backward. Forward establishes pt can spell; backward establishes organic mental syndrome, degree further established if pt unable to spell the 5-letter word by attempting 4, 3-letter words (e.g. “HAND”, “CAT”)
38
• Cranial Nerve testing
o CN 1 (Olfactory Nerve): Testing seldom reveals significant pathology, mb confused by nasal obstruction. mb helpful if frontal lobe lesion suspected (change in personality, hemiparesis, unexplained visual loss). Each side with a mild agent (soap or tobacco)
o CN 2 (Optic Nerve): Visual Acuity (near or far). Gross fields. Opthalmoscopic Exam
o CN 3, 4, 6 (Oculomotor, Trochlear, Abducens): Papillary reaction to light (PERRLA). Lateral gaze (X and H in space)
o CN 5 (Trigeminal): Stimulation of nerve distribution with light touch
o CN 7 (Facial): smile
o CN 8 (Vestibulocochlear): hearing fingertips moving
o CN 9, 10 (Glossopharyngeal, Vagus): gag reflex
o CN 11 (Spinal Accessory): shoulder elevation
o CN 12 (Hypoglossal): stick out the tongue
39
• Motor System
o Atrophy? Hypertrophy? Fasciculations or other involuntary movements?
o Key Tests: (tests often invalid if pt cannot perform dt pain)
o Drift of upper extremity (and lower if necessary): Have pt close eyes and hold arms horizontally forward, palm up for 15-30 sec; If +, hand will drop and rotate in (pronate)
o Hand grasp and toe dorsiflexion: Weakness common in UMNL. Cross hands, have pt. grasp index and middle fingers. Move toe and foot against resistance
o Muscle strength
40
• Coordination
o Finger-to-nose and Heel-to-shin; Cerebellar lesions: awkwardness of movt
o Rapid alternating movements: Slowness may result from cerebellar lesion
41
• Balance, gait
o Tandem gait (walk heel to toe)
o Rhomberg:
o We all need 2/3 senses to maintain balance: Vision, Vestibular sense, Proprioception
o (+) test → pt sways when eyes closed; either vestibular or proprioceptive defect
o If pt. sways when eyes open, not (+) → suspect cerebellar lesion
42
• Sensory Testing
o Pain: Sharp and dull testing
o Proprioception, stereogenesis, vibration: pts. eyes closed, bend big toe up and down, test vibration w tuning fork. ↓proprioception in MS. Elderly usu have ↓vibratory sense (does’t necessarily indicate a lesion)
o Light Touch: Double simultaneous stimulation
43
• Reflex Testing
o Major reflexes: Triceps, Biceps, Knee Jerk, Ankle Jerk, Babinski: + (abnormal dorsiflexion of great toe and fanning of other toes)→ UMNL
o Normal responses are symmetrical
o Asymmetry generally more reflective of pathology
o Tests for meningeal irritation (r/o meningitis or subarachnoid hemorrhage). Kernig: (+) →pain in low back on straightened lower extremity). Brudzinski: (+) = flexion of neck → marked neck pain, involuntary flexion of hip and lower extremities
44
• Neurological Diagnostic Procedures
o Basic Labs: CBC, CMP, TSH, Bedside glucose
o Additional testing to consider: Celiac (anti-gluten Abs, TTG); Heavy metal testing (whole blood, hair analysis, urine w & w/o provocation); Environmental testing for solvents, pesticides, etc
o Imaging and further studies: Lumbar Puncture, CT, MRI, MRA, MRV, Echoencephalography, Cerebral Catheter angiography, Duplex Doppler US, Myelography, EEG, Measurement of evoked responses (potentials), EMG and nerve conduction studies, Bx
45
• Cerebrovascular Accident (Stroke)
o sudden interruption of cerebral blood flow → neuro deficit, brain damage. 3rd mc cause death, mc cause of neuro disability
o Involves arteries to brain and subsequent distribution
o Anterior Supply (2/3 of brain): Internal Carotid. Strokes typically have UL sxs
o Posterior Supply (posterior portion of temporal and parietal lobes, brainstem, cerebellum): Vertebrobasilar. Strokes can have UL or BL sxs, more likely to affect consciousness
46
• Risk Factors for stroke
o Prior stroke, ↑ age, FHx stroke, Alcoholism, Male sex, HTN, Cigarette smoking, Hypercholesterolemia, DM, Use of certain drugs (eg, cocaine, amphetamines)
47
• Ssx of Stroke in general
o sxs occur suddenly
o Numbness, weakness, paralysis of contralateral limbs, face
o Aphasia, Confusion, HA
o Visual disturbances in one or both eyes
o Dizziness or loss of balance and coordination
48
• Types of stroke:
Ischemic Stroke (80%): thrombosis, emboli, lacunar, TIA (transient ischemic attack)
Hemorrhagic (20%): intracerebral hemorrhage, subarachnoid hemorrhage (SAH)
49
• Ischemic stroke dt thrombosis
o MC: Atherosclerotic plaques: can occur in any major cerebral artery: mc at sites of turbulent blood flow (branching of vessels)
o Less Common: Vascular inflam dt infx, Hypercoagulability dos, Older OCPs
50
• Ischemic stroke dt emboli:
o May lodge anywhere in cerebral tree
o May originate from Cardiac thrombi: Atrial fibrillation, Rheumatic heart dz (usu mitral stenosis), Post-MI, Vegetations on heart valves in bacterial or marantic endocarditis, Prosthetic heart valves
o Rarely: Fat emboli (from fractured long bones), Air (decompression sickness), Venous clots (pass from R →L heart thru patent foramen ovale
51
• Lacunar and TIA ischemic stroke:
o L: aka small vessel dz; Destruction of small arteries that supply deep structures; Occur more in elderly pts w DM or poorly controlled HTN
o T: Common in pts. w internal carotid artery dz; Sxs last under 1hr; Often do not cause brain damage; Usu precede stroke onset by a few days or mos
52
• Pathophysiology of ischemic stroke:
o Most blood flow, even if inadequate, can be compensated for by collateral arteries. Discompensation of collateral flow → ↑ chance of stroke
o Neurons die if ↓ flow but extent of damage depends on severity of ischemia
53
• ssx of ischemic stroke:
o Depend on part of brain affected: Patterns of neurologic deficit often suggest affected artery (correlation is NOT exact)
o Embolic stroke: Quicker onset of neuro deficit: minutes, Often during day, HA may precede
o Thrombotic stroke: usu at night, noticed on first waking; May have slower onset of sxs: over 24-48hrs (aka “evolving stroke” or “stroke in evolution”); Evolving stroke: UL neuro dysfxn often begins in one arm, spreads ipsilaterally; Extends W/O HA, pain, fever
o Lacunar: Pure motor hemiparesis; Pure sensory hemianesthesia; Ataxic hemiparesis
54
• Dx of ischemic stroke:
o Usu clinical
o Neuroimaging: CT: Done first to exclude intracerebral hemorrhage; MRI: Generally done 2nd; many smaller infarcts may only be found with MRI
o Bedside glucose testing (r/o hypoglycemia)
55
• DDx of ischemic stroke:
o Hypoglycemia, Postictal paralysis, Hemorrhagic stroke, Migraine, Tumor, Syncope, Systemic condition: Guillian Barre, Bell’s Palsy
56
• Hemorrhagic stroke dt Intracerebral Hemorrhage, etio:
o Focal bleeding from blood vessel in brain parenchyma
| o Causes: usu HTN; less common Arteriovenous Malformations (AVMs), Aneurysm, Trauma, Brain tumor, Bleeding do
57
• Ssx of intracerebral hemorrhage:
o Focal neuro deficit w/: HA, Nausea, Impairment of consciousness
o N/V, Delirium, Focalized or generalized seizures
o st dependent on location: Hemisphere (Hemiparesis); Posterior Fossa (Brain stem and cerebellar dysfxn)
58
• Dx and ddx of intracerebral hemorrhage:
o Dx: CT or MRI; Bedside blood glucose
| o DDX: Ischemic stroke, Subarachnoid hemorrhage, Hypoglycemia, seizure
59
• Subarachnoid Hemorrhage (SAH) stroke:
o sudden bleeding into subarachnoid space
o Etio: mc ruptured aneurysm
o Sxs: Sudden severe HA w LOC, HA peaking in seconds. Severe neuro deficits. Seizures possible. No neck stiffness initially but chemical meningismus may appear with vomiting
o Dx: Non-contrast C; if negative, lumbar puncture; blood in CSF
60
• Delirium and Dementia
o mc causes of cognitive impairment
o Delirium and Dementia are very similar, often hard to distinguish. Both have disordered cognition but:
o Dementia affects mainly memory
o Delirium affects mainly attention
61
• Key features of delirium:
o Onset: sudden, definite beginning pt
o Duration: days to weeks, mb longer
o Cause: almost always another condition (eg infx, dehydration, use or w/d of certain drugs)
o Course: usu reversible
o Effect at night: almost always worse
o Attention: greatly impaired
o Level of consciousness: variably impaired
o Orientation to time and place: varies
o Use of language: slow, often incoherent, inappropriate
o Memory: varies
o Need for medical attention: immediate
62
• Key features of dementia:
o Onset: Slow and gradual, with uncertain beginning point
o Duration: Usu permanent
o Cause: Usu chronic brain do (eg, AD, Lewy body dementia, vascular dementia)
o Course: Slowly progressive
o Effect at night: Often worse
o Attention: Unimpaired until dementia has become severe
o Level of consciousness: Unimpaired until dementia has become severe
o Orientation to time and place: Impaired
o Use of language: difficulty finding right word
o Memory: Lost, especially for recent events
o Need for medical attention: Required but less urgently
63
• Delirium:
o Usu caused by acute illness or drug toxicity; Often reversible
o Can occur at any age; mc in elderly; If younger: usu dt drug use or life-threatening systemic do
o Etio: Extensive, but mc are: Drugs, esp anticholinergics, psychoactive drugs, opioids; Dehydration; Infection; Idiopathic in 10-20%
64
• Delirium Pathophysiology
o Mechanism not fully understood but may involve: Reversible impairment of cerebral oxidative metabolism; Multiple neurotransmitter abnormalities; Generation of cytokines.
o Stress ↑ sympathetic tone, ↓parasympathetic tone which impairs cholinergic function and contributes to delirium
65
• Delirium ssx:
o Difficulty focusing, maintaining or shifting attention
o Fluctuating consciousness
o Disorientated to time and sometimes to place. May have hallucinations, delusions, paranoia
o Confusion
o Changes in personality or affect
66
• Delirium hx:
o Careful hx (interview family members, caregivers, friends), thorough review of medications, medical records. Alcohol use? Illicits? OTC and Rx meds?
o MSE
67
• Required for Dx of delirium:
```
o Acute change in cognition that fluctuates during day
o Inattention (eg, difficulty focusing or following what is said)
o Plus 1 of following: Disturbance of consciousness (i.e., reduced clarity and awareness of environment) with DSM; An altered level of consciousness (eg, hyperalert, lethargic, stuporous, comatose) or disorganized thinking (eg, rambling, irrelevant conversation, illogical flow of ideas) w CAM
```
68
• PE for delirium:
o Vital signs: Fever, meningismus, or Kernig and Brudzinski signs suggest CNS infx
o Hydration status
o Potential foci for infx: Tremor and myoclonus suggest uremia, liver failure, drug intoxication, certain electrolyte dos (eg, hypocalcemia, hypomagnesemia). Ophthalmoplegia and ataxia suggest Wernicke-Korsakoff syndrome
o Skin, head, neck: Scalp or facial lacerations, bruising, swelling, other findings suggest head trauma.
o Neuro exam: Focal neuro abnormalities (eg, cranial nerve palsies, motor or sensory deficits) or papilledema suggests a structural CNS do
69
• Labs/Imaging for delirium:
o First Set: CT or MR, Tests for suspected infx (CBC, Blood Cultures, UA, Chest film), Electrolytes, BUN, Creatinine, Plasma glucose, Blood levels of any drugs, Urine drug screen
o If Dx still unclear, may consider: LFTs, serum Ca, albumin, TSH, vit. B12, ESR, ANA, testing for syphilis (RPR or VDRL)
o If Dx remains unclear, may need further tests: CSF, serum NH3, heavy metal testing
70
• Delirium px:
o Morbidity and mortality higher in hospitalized patients
o Delirium dt certain conditions usu resolves w tx but mb slow
o For up to 2 yr after a delirium event: ↑ risk of further decline
71
• Dementia, etio:
o Usu dt anatomic changes in brain, primary dz of brain or other causes
o Slower onset; usu irreversible
o mc: AD, Vascular Dementia, Lewy Body Dementia and PD Dementia, HIV-associated Dementia, Frontotemoral Dementia, normal pressure hydrocephalus
o Also: HD, Progressive supranuclear palsy, CJD, Gerstmann-Sträussler-Scheinker syndrome, Other prion dos, neurosyphilis
72
• “Reversible Dementia”?
o w tx, these dos may clear signs of dementia (some experts reserve term dementia for those with only irreversible causes)
o Structural Brain Dos: Normal Pressure Hydrocephalus
o Metabolic Dos: Hypothyroidism, B12 def
o Toxins: Lead
73
• Ssx of dementia:
o Impairs cognition globally
o Onset is gradual
o Short-term memory loss may be 1st sign
o Personality and behavioral disturbances may develop early or late
o Motor and other neuro deficits (occur at different stages depending on type of dementia)
o ↑ Incidence of seizure
o Psychosis in 10%
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• Stages of Dementia
o Early: Recent memory impaired, mb progressive difficulty w independently doing ADLs (balancing checkbook, remembering where they put things, etc.); mbagnosia, apraxia, aphasia; mb beginning of personality changes
o Intermediate: Inability to learn and recall new info; Memory of remote events reduced but not lost; May need help with basic ADLs (bathing, eating, dressing, toileting); Loss of sense of time and place (ambulatory but often get lost, at risk of falls dt confusion)
o Late: Cannot walk, feed themselves, or do any other ADLs; mb incontinent, unable to swallow; End-stage usu → coma or death, usu from infx
75
• Hx, PE, Labs, ddx, px of dementia:
o Hx (w pt and someone who knows pt): MSE
o PE: Complete neuro
o Neuropsychological Testing: if hx and bedside MMSE are inconclusive
o Labs: TSH, B12, CBC, LFTs, Consider HIV or RPR if (syphilis?) suspected
o Imaging: CT or MRI
o Ddx: Delirium, Age-associated memory impairment, Mild cognitive impairment, Cognitive sxs related to depression
o Px: Generally a progressive dz, shortens lifespan but course depends on cause and tx options
76
• Required to dx dementia:
o Cognitive or behavioral (neuropsychiatric) sxs interfere w ability to function at work or ADLs
o Ssx= decline from previous levels of functioning; not explained by delirium or major psychiatric do
o And cognitive or behavioral impairment should have 2+ of following:
o Impaired ability to acquire and remember new info (amnesia)
o Language dysfxn (aphasia)
o Visuospatial dysfxn (agnosia; eg, inability to recognize faces or common objects)
o Impaired executive function, including reasoning, handling of complex tasks, and/or judgment (apraxia)
o Changes in personality, behavior, comportment
77
• AD, incidence
o Progressive cognitive deterioration dt B-amyloid deposits and neurofibrillary tangles in cerebral cortex and subcortical gray matter
o mc cause of dementia (60-80% of dementia in elderly)
o In US 13% of people > 65, 45% of people > 85 have AD
o F:M 2:1 (partly b/c F have greater life expectancy)
o Early-onset (presenile) forms of AD are rare ( > 5% of cases worldwide)
78
• AD etio:
o usu sporadic w late onset ( > 65), unclear etio
o Best predictor is age
o Genetic component: 5-15% are familial; At least 5 distinct genetic loci on chromosomes 1, 12, 14, 19, 21 influence initiation and progression of AD; Mutations in amyloid precursor protein; Mutations in Apolipoprotein E alleles
o No definite links but under study: ↑ hormone levels; Metal exposure
79
• AD Pathophysiology:
o Neurodegeneration dt inappropriate deposition of protein -amyloid in brain, formed during processing of amyloid precursor protein (APP) (extracellularly). APP encoded on chromosome 21; trisomy 21 will all develop AD by a35. 2 known membrane-bound proteins called presenilins also contribute to APP processing: PS 1 & 2
o Neurofibrillary tangles. Number and distribution of tangles directly related to severity of dementia. Formed intracellularly and consist of a microtubule-associated protein, tau, has vital role in maintenance of neuronal cytoskeleton structure and function. Tau is hyperphosphorylated in AD.
o Gradual loss of specific neurotransmitters. Acetylcholine is earliest and most prominent
80
• AD Risk Factors
o Most consistent: ↑ age, FHx (esp. if 1st deg relatives); ApoE genotype; Trisomy 21 (AD develops in all by 35 dt ↑ deposition of B-amyloid)
o Others: HTN, Stroke, ↑fasting homocysteine levels
81
• AD ssx:
o Early, intermediate and late stages (see Dementia in general)
o Loss of short term memory usu 1st sign
o ↑ forgetfulness (can’t remember words, names, disorganization of bills and meds, burnt pots on stove)
o ↑ repetitiveness: Ask same question over and over; have same conversation minutes after it was completed
o Behavioral sxs become common: Suspicious or paranoid behavior; Agitation, yelling, wandering
82
• AD ddx:
o absence of motor deficits helps to differentiate AD from most other dementias
o However, as AD progresses, Parkinsonism can become evident making differentiating AD from Lewy body dementia more difficult
o Use of Modified Hachinski Score can help differentiate from Vascular dementia
83
• AD hx:
o Subjective complaint of memory loss not useful since common in elderly individuals
o Traditional Criteria for Dx includes all of following:
o Dementia established clinically and documented by formal MSE
o Deficits in 2+ areas of cognition
o Gradual onset and progressive worsening of memory and other cognitive functions
o No disturbance of consciousness
o Onset > 40, usu > 65
o No systemic or brain dos that could account for progressive deficits in memory and cognition
84
• AD MSE, PE, work-up, px:
o MMSE somewhat insensitive to milder stages of AD; Impaired encoding of info, poor naming, construction impairment, disorientation characterize memory loss in AD
o PE: Complete neuro exam
o Labs: No standard panel to dx AD but consider basic labs mentioned above (Dementia in General); Apo E genotyping is NOT dx of AD, should not be used (May only heighten anxiety unnecessarily); CSF (B-amyloid or tau protein in CSF)
o Imaging: MRI or CT; May show ↓ volume
o Px: Avg survival from Dx is ~ 7 yrs, varies, st 20 yrs
85
• Vascular dementia:
o Acute or chronic cognitive deterioration dt diffuse or focal cerebral infarction usu related to cerebrovascular disease (CVD); mb single or a series of episodes
o 2nd mc dementia in elderly
o mc w vascular risk factors: HTN, DM, Hyperlipidemia, Smoking, Several strokes
o Types: Multiple lacunar infarction, Multi-infarct dementia, Strategic single-infarct dementia, Binswanger dementia (subcortical arteriosclerotic encephalopathy)
86
• Vascular dementia ssx, dx, px:
o Similar to other dementias; As progresses may show focal neuro deficits: Exaggeration of DTRs; Extensor plantar response; Gait abn; Weakness of an extremity; Hemiplegias; Pseudobulbar palsy w pathologic laughing and crying; Other signs of extrapyramidal dysfx
o Dx: Hx: Reveals hx of a stroke; Can use Hachinski Ischemic score to differentiate from AD; Imaging: CT and MRI may show multiple BL infarcts
o Px: 61% 5 yr mort rate
87
• Lewy Body Dementia and PD Dementia
o Lewy Body Dementia: characterized by cellular inclusions, called Lewy bodies, in cytoplasm of cortical neurons
o PD Dementia: a movt do, but dementia can form late in dz. Dementia is from Lewy bodies in substantia nigra
o 3rd mc dementia
o Age of onset: > 60
88
• Ssx of LBD, PD
o L: Cognitive and extrapyramidal sxs usu begin within 1 yr of each other (unlike Parkinson Dementia): Tremor occurs late; Rigidity of axial muscles w gait instability occurs early; Deficits tend to be symmetric
o Fluctuating Cognitive Function: Short term recall affected less than digit span memory; Visual Hallucinations; Sleep Dos
o P: Cognitive sxs don’t begin until 10-15 yrs after motor sxs; Psychiatric sxs (hallucinations, delusions) less frequent than LBD
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• Sx of LBD/PD. Px:
o Dx is clinical but sensitivity and specificity poor; Neuroimaging ; CT and MRI show no characteristic changes but done to r/o other factors
o L: Probable if 2/3 are present: Fluctuations in cognition, Visual hallucinations, Parkinsonism
o P: More probable if motor sxs are more severe and precede cognitive sxs; Definitive dx requires autopsy samples of brain tissue
o For both: course is progressive and px is poor
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• HIV-associated Dementia
o Chronic cognitive deterioration dt brain infx by HIV; Unlike almost all other forms of dementia, usu in younger people; mb dt HIV virus itself or other opportunistic infx
o Ssx: Similar to other forms of dementia
o Dx: Initial work-up similar to other dementia; CT or MRI to check for signs or CNS infx
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• Frontotemporal Dementia, path, types:
o sporadic, hereditary dos affect frontal and temporal lobes, including Pick Dz
o 10% of all dementias; usu younger (avg 55-65); M=F, FHx in 50% of cases
o Pathogenesis: 1) Gliosis, neuronal loss, spongioform degeneration in superficial layers of frontal and temporal lobes; 2) Pick cells (large ballooned neurons) in under 25% of cases. Pick bodies= round cytoplasmic inclusions, form in small neurons, pathognomonic for Pick Dz if in dentate gyrus
o Subtypes: Frontal Variant FTD, Primary Progressive Aphasia (PPA), Semantic Dementia
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• Ssx, dx, px of frontotemporal dementia:
o Ssx: Affects personality, behavior, usu language function more and memory less than AD (striking behavioral and personality changes). Major breakdown in social behavior, personal hygiene and affect
o Dx: suggested by clinical findings ; Blood work and CSF not particularly helpful; MRI May show severely thin atrophy in frontal and temporal lobes (st not until late in dz)
o Px: Usu. gradual progression but can vary; Median illness duration is 8 yrs (range 2-20)
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• Normal Pressure Hydrocephalus
o thought to result in a defect in CSF resorption by arachnoid granulations
o ssx: Gait disturbance (Non-specific unsteadiness and impaired balance), Urinary incontinence, Dementia (mb not until late), Enlarged brain ventricles, Normal or slightly ↑ CSF pressure; Magnetic gait (feet appear stuck to floor) is characteristic
o Dx: Clinical Eval, Neuroimaging, CSF Reveals normal to slightly ↑ pressure
