Exam 6 (no drugs) Flashcards
Demyelination causes clinical symptoms because of?
Conduction block
Guillain-Barre syndrome
- describe presentation
- diagnosis
- treatment
- can cause death due to to
DEMYELINATING PERIPHERAL NEUROPATHY
- Presentation
- ascending paralysis
- loss of reflexes - CSF Findings
- elevated protein - Treatment
- IVIG
- mechanical ventilation if required - Death due to respiratory failure
Multiple sclerosis epidemiology
- age group
- gender
- hereditary?
- latitude
- 95% in ages 15-50
- 2nd most common cause of neurological deficit in the age group - 2/1 = female/male
- Yes there’s a hereditary component
- Higher risk if spend adolescence in temperate zone
MS lesions tend to cluster in which areas? significance?
Where white matter is in direct contact w/ CSF
Explains the vision loss, walking issues (cerebellum) and bladder dysdx
Why are psychiatric and behavioral changes associated w/ MS?
B/c it hits the frontal lobe
Compare old vs new MS lesions on MR
New/active lesions - contrast enhancement
Old lesions - increased signal on T2 w/out enhancement
Explain internuclear ophthalmoplegia
Bilateral INO pathognomonic for?
Damage to the MLF
-nystagmus when abducting eye on affected side and unable to adduct the opposite eye
Bilateral INO seen in MS due to demyelination of the MLF
List 8 clinical findings associated with MS. (Goljan)
- Sensory dysfx
- UMN dysfx
- including babinski - Autonomic dysfx
- urge incontinence
- sexual dysfx
- bowel motility problems - Optic neuritis
- inflammation of optic nerve
- blurry or sudden loss of vision - Cerebellar ataxia
- Scanning speech (sound drunk)
- Intention tremor (nystagmus)
- Bilateral INO
What test can be used to assess for evidence of primary demyelination/remyelination pathophysiology?
Visual evoked potentials
-delay after remyelination occurs
CSF findings in MS
ALWAYS IMAGE FIRST
- slight pleocytosis (10-15 lymphocytes)
- Elevated CSF index (>0.6) -> too much IgG present in CSF relative to plasma
- Oligoclonal bands
- measure IgG spikes
- compare to serum
- allowed to have one more than what is present in the serum
What’s one thing you should always check for when MS exacerbation is suspected?
INFECTION
Central pontine myelinolysis
- pathophys
- cause by
- increased risk from
- clinical presentation
- imaging
- Path - demyelination of ventral pons
- Caused by rapid correction of hyponatremia
- Increased risk from malnutrition and alcohol
- Locked in state, quadriplegia or even coma
- Imaging
- Increased T2 signal in the pons
- trident sign
PML tends to attack which area of the brain? What sxs are seen? What is the time course?
Posterior areas
Aphasia, visual defects and hemiparesis
Subacute to chronic onset
Diagnosis for PML
- MRI
- CSF
- Serum
- MRI
- non-enhancing
- no mass effects - CSF
- pcr for JCV virus - Serum
- Serum JC antibodies (found in 60-80% of population)
What is IRIS and it’s association with PML?
- Reconstituting immune system leading to intense inflammatory reaction in region of PML
- Can cause herniation
- Seen when AIDS patients put on triple therapy (HAART)
Acute Disseminated Encephalomyelitis
- onset time course
- Follows what?
- how can it lead to death
- MRI findings
- CSF
- Treatment
- Onset
-rapid (hours to days)
headache -> lethargy -> coma - Follows viral infection or vaccination
viral -> express Ag that cross reacts w/ myelin
vaccination -> measles - Death due to cerebral edema and mass effect if not txed
- MRI
- Gadolinium enhancement of white matter
- remember PML is non-enhancing - CSF
- moderate lymphocytic pleocytosis (50-100 cells)
- elevated protein
- oligoclonal bands (less common) - Treatment
- IV methylprednisolone (1000 mg)
- hemicraniectomy may be necessary
Charcot Marie Tooth Disease
- which type of neuropathy?
- progression time?
- rarely complain of?
- inheritance?
- length dependent sensorimotor peripheral neuropathy
- progresses over years to decades
- rarely complain of numbness or tingling
- autosomal dominant
CMT-1 conduction velocity (slow or fast)
compare the 3 types of CMT-1
CMT1 has very slow conduction velocities (dysmyelinating)
CMT1A
- PMP22 duplication
- 75% of all CMT1
CMT1B
-myelin protein zero
20% of all CMT1
CMT1X
- looks like CMT1 but never has male to male inheritance
- connexin 32
CMT-2 conduction velocity (slow or fast)
normal motor conduction velocity
What is the most common hereditary ataxia?
Friedreich’s ataxia
Friedreich’s ataxia
- inheritance
- gene involved and what does it code for
- age group
- sx triad
- other systems associated
- tx
- autosomal recessive
- Frataxin gene deficiency (9q13)
- trinucleotide repeat disorder
- deficiency leads to impaired mitochondrial iron homeostasis
- cells are more prone to apoptosis - Adolescent and young adults - slow onset
- Triad
- absent ankle reflexes (peripheral neuropathy)
- bilateral babinski
- dysmetria (ataxia) - Multisystems
- hypertrophic cardiomyopathy (major)
- diabetes (1:4)
- scoliosis (1:4)
6. Tx –Treat diabetes –Correct scoliosis –Manage hypertrophic cardiomyopathy • vigilant blood pressure control
Suspicion for Huntington’s based on?
Age of onset?
Huntington gene?
MRI findings?
Best test to dx?
How do you tx?
Triad
- psychiatric/cognitive probs
- chorea
- dominant inheritance
Age
5-70 (usually 25-45)
Huntington gene (expanded GAG repeats; chromosome 4)
MRI - caudate atrophy/diffuse atrophy
-these occur later
GENETIC TESTING IS BEST
Treatment
-Atypical and traditional antipsychotics can help
psychosis, SSRIs depression, anxiolytics for anxiety
-No treatment effective for primary process
ALS
- clinical presentation
- what’s spared
- inheritance?
- cognition?
- pathogenesis
- dx
- treatment
- clinical presentation
- UMN and LMN signs
- usually starts in intrinsic muscles of the hands - sensation, bladder/bowel fx and eye control are spared!
- 5-10% dominantly inheritance
- Cognition spared but subset have frontotemporal dementia
- Mutated or misfolded SOD1 leading to apoptosis of neurons
- Dx of exclusion
- MRI
- EMG
- FVC - Treatment
Riluzole - glutamate antagonist
What is the safety margin percentage beyond which patients with alzheimer’s start to display symptoms
20%
List all the histological changes associated with Alzheimer’s. What location do you expect these changes to occur? (be able to recognize the image)
Cerebral cortex and hippocampus
- neuritic plaques
- neurofibrillary tangles
- granulovacuolar degeneration
- congophilic angiopathy: beta amyloid
- Hirano bodies
The Pittsburgh compound binds to what? How is it visualized?
Binds to amyloid deposits
Visualized on PET scan
Frontotemporal lobar degeneration often initially presents with what? Often misdxed as?
Late stage sxs?
EARLY
Personality and behavior changes
-Misdxed as psychiatric disorder
LATE
- gradual reduction in speech
- akinesia and rigidity
Highlight some of the differences b/w (there are 2)
FTD
- earlier onset compared to AD
- at an early stage, do not cause the memory loss and visuo-spatial disorientation that are so characteristic of AD
What cortical areas are affected with FTD (there are 5)
- ACC
- Frontal insula
- Frontal pole
- Orbitofrontal cortex
- Temporal pole
Pick’s disease
- age of onset
- inheritance
- clinical course
- area of brain affected
- compensatory mechs
- tx
- age around 60
- sometimes autosomal dominant
- clinical course 2 - 5 years (dead)
- Extreme frontotemporal atrophy (knife like gyria)
- compensatory hydrocephalus
- no tx
Huntington’s disease
- inheritance
- age range
- late manifestations (decade of life)
- early changes
- late changes
- Inheritance
- autosomal dominant - Age range
- 20 to 50 - Late manifestations
- 4th to 5th decades - Early changes
- personality and depression - Choreiform movements, jerking and dementia
Huntington’s genetics
- which chromosome affected
- type of mutation
- chromosome 4
- expanded unstable trinucleotide (CAG) repeat -> more repeats = earlier onset of disease
Which regions of the brain are damaged in Huntington’s?
What’s the structural consequence of these changes?
Marked atrophy of the caudate nucleus
- loss of small to medium sized neurons
- fibrillary gliosis (astrocytosis)
Putamen and cortical atrophy
-variable
Ex vacuo dilations of the anterior horns of lateral ventricles
ALS
- UMN or LMN?
- Males vs females
- age
- breakdown of sporadic vs familial
- Which chromosome (what does it code for)
- Both UMN and LMN
- UMN -> prefrontal cortex
- LMN -> CN nuclei and anterior horn cells of SC - Males > females
- Age > 40
- 90% sporadic; 10% familial
- Chromosome 21q
- codes for superoxide dismutase
- toxic action of mutated enzyme -> decreased zinc binding capacity
ALS clinical presentation
Initial presentation - asymmetrical weakness
LMN: muscle atrophy, weakness, fasciculations
UMN: weakness and spasticity
Progressive w/ loss of all voluntary movement; death from respiratory failure or sepsis
Intellect unimpaired
ALS variants
- progressive bulbar palsy
- progressive muscular atrophy
- primary lateral sclerosis
- Cranial nerve involvement
- dysarthria, dysphagia and respiratory compromise - Predominant LMN involvement
- spinal cord anterior horn involvement - Confined to the corticospinal tract
- UMN
Friedreich’s ataxia
- inheritance
- mutation (which chromosome/type)
- function of the gene
- autosomal dominant
- Chromosome 9
- trinucleotide (GAA) expansion on gene coding for frataxin
- results in low levels of the protein
- frataxin plays a role in iron homeostasis in the mitochondria
- get mitochondrial iron accumulation
- cells are more prone to apoptosis
Friedreich’s ataxia
-sites of degeneration (from goljan = 5)
- DRG
- Posterior columns
- Spinocerebellar tracts
- lateral corticospinal tracts
- large sensory peripheral neurons
Friedreich’s ataxia
-clinical findings (5)
- progressive
- gait ataxia to ataxia of all extremities
- loss of tendon reflexes, cerebellar dysarthria
- impaired joint position, vibration
- pes cavus: arches feet, claw toes
Friedreich’s ataxia
-associated with (from goljan = 2)
- hypertrophic cardiomyopathy
- DM1 (10%)
What is the most useful diagnosis for CJD?
EEG - Slow (1-2 cycles/sec) generalized triphasic periodic sharp wave complexes
How does FLAIR MRI work? What is it good for?
- facilitates the visualization of ABNORMAL parenchymal water content resulting from pathology
- great for edema generating pathology and white matter lesions (such as MS)
What is the signature feature seen on microscopy with acute disseminated encephalomyelitis (ADEM)
- what’s lost?
- infiltrates?
narrow cuffs or sleeves of myelin loss around small veins
-cellular infiltrates in demyelinated areas are composed of macrophages
Is level of consciousness affected with dementia?
NOOOOOO
What’s the single most important treatable cause of dementia?
Pseudo-dementia secondary to DEPRESSION
Peripheral neuropathy with myelopathy suggests?
B-12 deficiency
-combination of increased and absent reflexes
Risk 3 causes of metabolic dementia
- Hypothyroidism
- DM
- repeated episodes of hypoglycemia
- risk factor for multi-infarct dementia - B-12 deficiency
- surgery
- anemia
Describe the spontaneous movements seen with the following diseases?
- Parkinsons
- Huntingtons
- Prions
- Tremors
- Chorea
- Myoclonus
Triad for normal pressure hydrocephalus
Describe the CSF
Triad
-dementia, gait apraxia, incontinence
CSF is normal (including pressure)
-no papilledema
List 4 risk factors for multi-infarct dementia
- HTN
- diabetes
- cardiac disease
- age
Nucleus basalis of Meynert
- affected in which disease?
- which NT produced here?
- Alzheimer’s
- cholinergic
List 3 brain pathologies that are more likely to occur in alcoholics
- subdural hematoma
- closed head injuries
- chronic meningitis
Which drug sometimes given to Parkinson’s disease patients causes dementia?
Cogentin (benztropine) -> anticholinergic
What are the initial sxs seen with dementia w/ Lewy bodies
what’s spared initially?
what follows the cognitive changes?
- visual hallucinations
- REM sleep disorders
- delirium
- memory initially spared (frontal and executive fxs affected)
- Parkinsonism follows
Frontotemporal dementia
- common as Alzheimer’s in which age group?
- what precedes memory probs?
- extrapyramidal findings?
- sparing of?
- 50 - 70
- Frontal lobe dysfx
- disinhibition, apathy, compulsion
- impaired judgement, planning and lack of insight - axial rigidity and dystonia
- Sparing of cholinergic system
DSM-IV classification for mental illness requires what 3 conditions?
- present distress
- disability
- increased risk of pain, death, disability or an important loss of freedom
Define the five axes used to classify diagnoses in the DSM-IV
What needs to be ruled out before axis I dx can be made?
Which one doesn’t have a pharmacological intervention?
Axis I - diagnoses for all major psychiatric disorders
-axis III must be ruled out first
Axis II - Diagnoses of personality or developmental disorders
-no pharm intervention
Axis III - diagnoses of other medical illnesses
Axis IV - current stresses
Axis V - level of functioning
Diagnostic criteria for major depressive disorder
SIG E CAPS
Episodes lasting 6-12 months.
Episodes = 5/9 of the following sxs for at least 2 weeks
- Sleep disturbance
- Loss of Interest (anhedonia)
- Guilt or feelings of worthlessness
- Loss of Energy
- Loss of Concentration
- Appetite/weight changes
- Psychomotor retardation or agitation
- Suicidal ideations
- Depressed mood
What are 4 key domains of development?
- gross motor
- fine motor
- speech
- social
Childhood febrile seizures - key points
- Age
- how common
- recurrence risk
- epilepsy risk
Age -> 6 months to 5 years
Fairly common
Recurrence risk - 1/3
Epilepsy risk - 2%
What’s an important difference b/w workup of simple febrile seizure vs non-fibrile seizure
Do imaging and get EEG with non-febrile
2 lesion causes that may cause focal seizures
Cysticercosis and AVM
Non-febrile seizures in children - key points
- Common
- Recurrence risk idiopathic
- Recurrence risk symptomatic
- Treat
- Safety
- Common - yes
- Recurrence risk idiopathic - 30%
- Recurrence risk symptomatic(e.g. lesion) - 70%
- Treat - not if it’s there first
- Safety
Describe focal seizure presentation
staring seizure w/ automatic behaviors (e.g. lip smacking) followed by ictal phase
Offset seen with absence epilepsy
Abrupt - child returns to normal awareness and activity
The term developmental delay is reserved for kids up until what age?
5 or 6
Head circumference in child indicative of CNS prob
2 SD below normal
CHECK IN KIDS UNDER 3
Diagnosis of delirium
Confusion assessment method
-requires 1 AND 2 and either 3 OR 4
○ #1 Acute and Fluctuating course ○ #2 Inattention ○ #3 Disorganized thinking ○ #4 Altered L.O.C. 
3 regions of the brain involved with delirium
- Prefrontal cortex
- anterior thalamus
- nondominant parietal and fusiform cortex
Mechanism of delirium
- cholinergic deficiency
- serotonin deficiency
- GABA and DA
- inflammation via cytokines (IL-2 or TNF)
List 4 predisposing risk factors for delirium
- Advanced age
- Preexisting dementia
- Functional impairment in ADL
- High medical comorbidities
- sever heart failure
Precipitating risk factors for delirium
I WATCH DEATH
• Infection:
-especially urine and respiratory tract
• Withdrawal:
-benzodiazepines, alcohol, lack of sensory input (poor vision, hearing)
• Acute metabolic:
-medication side effects, especially sedating or anticholinergics
• Trauma:
• CNS Pathology:
-intracranial hemorrhage, stroke, tumor
• Hypoxia:
-Acute myocardial infarction, pulmonary embolism, CHF or COPD exacerbation
• Deficiencies:
-B12, folate
• Endocrinopathies:
• Acute Vascular:
-stroke
• Toxins
• Heavy Metals (lead, mercury)

Identify 4 key steps in the management of delirium
- Identify and treat reversible contributors
- Maintain behavioral control
- Anticipate and prevent or manage complications
- Restore function in delirious pts.
2 drugs most likely to be the cause of delirium?
Alcohol and benadryl
Autonomic system activated in appetitive vs consummatory phases
Appetitive
-activation of motor behavior and sympathetic nervous system
Consummatory
-involves rest, sedation and activation of the parasympathetic nervous system
What is the pleasure center in the brain
- integration site for what structures?
- interface b/w which systems?
NUCLEUS ACCUMBENS (Pleasure center)
• Integration site for cortical (prefrontal cortex) and subcortical (VTA, amygdala) input
• Critical interface between limbic and motor
systems thus linking motivation and action
Common output pathway for drug reward is from nucleus accumbens to motor areas via the?
Ventral pallidum
Reward deficiency syndrome cause?
- due to a genetic deficiency in D2 DA receptor
- A1 allele carries -> 74% of developing on the the disorders associated with this syndrome
2 mechanisms through which alcohol mediates its effects?
-which receptor systems
Enhances action of inhibitory GABA receptor complex
DECREASES the actions of the excitatory NMDA receptor
Alcohol pharmacokinetics
- absorption
- metabolism
- elimination
ABSORPTION
- 1/4 through stomach
- rest through small intestines
METABOLISM
-liver
ELIMINATION
- 90% by oxidation in the liver
- 10% through lungs and kidneys
Alcohol pharmacodynamics
- basic MoA
- list the neurochemical targets
Basic MoA
-acts on membrane proteins and disrupts membrane functioning at high doses
Neurochemical targets
- GABA
- GLUTAMATE
- DA
- 5-TH
- OPIOIDS
Alcohol use disorder genetics
- how much do genetics play a role?
- number of genes involved?
- inheritance pattern
- 50%
- multiple
- male to male
Alcohol w/drawal
-time frame for seizures and delirium tremens
SEIZURES
- first 48 hours
- need to admit and tx
DELIRIUM TREMENS
- highest risk on days 3 to 5
- Symptoms in order of appearance: autonomic system hyperactivity (tachycardia, tremors, anxiety, seizures), psychotic symptoms (hallucinations, delusions), confusion.
- Treatment: benzodiazepines.
Acute vs chronic tolerance with nicotine use
Acute - activation and desensitization of NAChRs in CNS
Chronic - upregulation of NAChRs
5 A’s for brief intervention in nicotine users
-effect on quit rate?
• ASK-identify all nicotine users at every visit
• ADVISE-urge all nicotine users to quit
• ASSESS-determine willingness to make a
quit attempt
• ASSIST-Aid the patient in quitting
• ARRANGE-Schedule follow-up contact
• Repeated use → doubles quit rate
5 R’s to motivate nicotine users to quit
RELEVANCE
RISKS
REWARDS
ROADBLOCKS
REPETITION
Test for detecting heavy alcohol use in the past 4-7 days
Carbohydrate deficient transferrin (CDT)
Most sensitive way to determine alcohol in system
CDT + GGT
Probs with urinary drug screen when checking for opioid use
• Might not catch the synthetics – oxycodone, hydromorphone
• Fentanyl and methadone don’t show up typically
-May need to do an assay
craniosynostosis
-premature closure causes abnormal shape in skull as underlying brain grows
Muscles derived from the pharyngeal arches and nerves
Arch 1
- muscles of mastication
- V
Arch 2
- muscles of facial expression
- VII
Arch 3
- stylopharyngeus
- IX
Arch 4
- muscles of pharynx
- X (superior laryngeal nerve)
Arch 6
- muscles of larynx
- X (recurrent laryngeal nerve)
Sensory innervation for:
- oral and nasal cavities
- pharynx
- larynx
(think cranial to caudal)
- -CN V is GSA for oral and nasal cavities
- -CN IX is GVA for pharynx
- -CN X is GVA for larynx
Physical signs of first arch syndromes
which syndrome included?
Low set ears and small jaw
Treacher Collins
Tongue develops from which arches?
Parts of 1 - distal tongue bud
3 and 4 - hypopharyngeal eminence
Sensory innervation to mucosa of the tongue
- -CN V supplies sensory for anterior 2/3 of tongue (GSA)
- -CN IX supplies posterior 1/3 (GVA)
- -CN X supplies epiglottis (GVA)
Which tongue skeletal muscle is not innervated by hypoglossal?
Palatoglossus (CN X)
Thyroid gland develops as growth from
foramen cecum
Thyroglossal cyst
–cysts are remnants of thyroglossal duct
–on midline, associated with hyoid bone
–surgical removal includes removal of midline hyoid bone (Sistrunk procedure)
Derivatives of pharyngeal pouches
1st - middle ear
2nd - palatine tonsils
3rd - Thymus and inferior parathyroid gland
4th - superior parathyroid gland
C-cells of thyroid gland formed from
ultimobranchial body (neural crest)
DiGeorge syndrome
- signs
- which pouches
- organ systems
- defect in
- micrognathia (small jaw)
- agenesis of 3rd and 4th pouch derivatives (no thymus or PTHs)
- cardiovascular anomalies
- caused by defect in, or abnormal migration of, neural crest cells
Holoprosencephaly
syndrome resulting from improper development of the forebrain, causes facial anomalies
Fetal alcohol syndrome
Embryological separation of primary and secondary palate
incisive fossa
Pierre robin syndrome
3 things
micrognathia, cleft palate, glossoptisis
foster kennedy syndrome
- most common cause
- signs and sxs
-meningioma
signs and sxs
- ipsilateral anosmia -> olfactory bulb
- ipsilateral optic atrophy -> optic nerve
- contralateral papilledema -> inc ICP
Medial medullary syndrome
- infarct of which artery
- causes
- penetrating branches of anterior spinal artery
- alternating hypoglossal hemiplegia
