Steve Nash's Neuro Assists Flashcards
Where does Herpes labialis go dormant
Trigeminal ganglia
HSV-1
Where does Herpes genitalis go dormant
sacral ganglia
HSV-2
Where does Herpes zoster go dormant
Dorsal root or trigeminal ganglia
Which elements of the neural cytoskeleton form neurofibrillary tangles in alzheimer’s disease
Microtubules
Notochord induces what
Induces overlying ectoderm to differentiate into neuroectoderm and form the neural plate
Neural plate gives rise to the
neural tube and neural crest cells;
Notochord becomes what
Notochord becomes nucleus pulposus of the intervertebral disc in adults;
Alar plate
Dorsal spinal cord;
gives to sensory
Basal plate
Ventral spinal cord;
Gives rise to motor
Prosencephalon develops into
Telencephalon and diencephalon;
Mesencephalon develops into
Mesencephalon;
Rhombencephalon develops into
Metencephalon and myelencephalon;
Telencephalon gives rise to
Cerebral hemispheres;
Lateral ventricles
Diencephalon gives rise to
Thalamus;
Third ventricles
Mesencephalon gives rise to
Midbrain;
Aqueduct
Metencephalon gives rise to
Pons and cerebellum;
Upper part of fourth ventricle
Myelencehalon gives rise to
Medulla;
Lower part of fourth ventricle
In the brain, what does the neuroectoderm give rise to
CNS neurons;
ependymal cells (inner lining of ventricles, make CSF);
oligodendroglia;
astrocytes
In the nervous system, what does the neural crest give rise to
PNS neurons;
Schwann cells
In the nervous system, what does the mesoderm give rise to
Microglia (like macrophages, originate from mesoderm)
Neural tube defects: when do they happen, what are the findings
neuropores fail to fuse (4th week);
Elevated alpha fetoprotein (AFP) in amniotic and maternal serum;
increased AChE in amniotic fluid confirms (fetal AChE in CSF transudates across defect into amniotic fluid)
Spina bifida occulta
Failure of bony spinal canal to close, but no structural herniation;
Dura is intact;
associated with tuft of hair or skin dimple at level of bony defect
Meningocele
Meninges (but not the spinal cord) herniate through spinal canal;
normal AFP
Meningomyelocele
Meninges and spinal cord herniate through spinal canal defect
Spina bifida with myeloschisis
Spinal cord visibly seen;
increased AFP
Anencephaly
Malformation of the anterior neural tube resulting in no forebrain, open calvarium (frog like appearance);
Findings: increased AFP, polyhydramnios (no swallowing);
associated with maternal diabetes type I;
maternal folate intake decreases chances
Holoprosencephaly
Failure of left and right hemispheres to separate;
Usually occurs during weeks 5 and 6;
complex multifactorial etiology that may be related to mutations in sonic hedgehog signaling pathway;
Moderate form has cleft lip/palate, most sever form results in cyclopia;
Associated with Patau
Lissencephaly
smooth brain with no gyri;
lack of hemisphere sulci;
severe neurologic impairment
Chiari II (arnold chiari malformation)
Significant herniation of cerebellar tonsils and vermis through foramen magnum with aquaductal stenosis and hydrocephalus;
Often presents with lumbrosacral myelomeningiocele and paralysis below the defect
Dandy Walker
Agenesis of cerebellar vermis and cystic enlargement of 4th ventricle (fills the enlarged posterior fossa);
Associated with hydrocephalus and spina bifida;
Chiari I malformation
Usually seen in adults;
less significant herniation of cerebellar tonsils into magnum foramen;
Valsalva makes worse;
Usually asymptomatic
Syringomyelia
Cystic cavity (syrinx) within the spinal cord (if central then it is called hydromyelia);
Crossing anterior spinal commissural fibers are typically damaged first leading to cape like bilateral loss of pain and temperature sensation in upper extremities;
Mostly at C8 T1 level;
Associated with Chiari 1 malformation;
Tongue development
1st and 2nd branchial arches form the anterior 2/3 (taste is CN 7 and sensation is CN V3);
3rd and 4th give rise to posterior 1/3 (taste and sensation is CN 9, very posterior taste is 10);
motor is CN12;
Muscles of the tongue are derived from occipital myotomes
Stain used for neurons
Nissl Substance (Stains RER, which is only present in dendrites and cell bodies, NOT axons)
If an axon is injured it undergoes what
Wallerian degeneration;
degeneration distal to injury and axonal retraction proximally;
allows for potential regeneration of axon if in PNS (CNS will never regenerate unless it is the olfactory nerve)
Astrocyte
Physical support, repair, K metabolism, removal of excess neurotransmitter, foot process are component of the BBB, glycogen fuel reserve buffer;
Reactive gliosis in response to neural injury;
Astrocyte marker is GFAP;
Derived from neuroectoderm
Microglia
CNS phagocytes;
derived from bone marrow bone monocytes (mesodermal origin);
not readily seen in Nissl stains;
Have small irregular nuclei and relatively little cytoplasm;
Scavenger cells of CNS;
respond to tissue damage by differentiating into large phagocytic cells;
Is an Antigen presenting cell;
Secretes free radicals;
HIV infected microglia fuse to form multi-nucleated giant cells
Oligodendroglia
Myelinates neurons of the CNS;
1 oligodendroglia can myleniated around 30 to 50 nerves;
Derived from neuroectoderm;
fried egg appearance;
MS, progeressive multifocal leukoencephalopathy, and leukodystrophies attacks this cell type;
Glial cells
Supporting cells of the CNS;
capable of cell division
Schwann cells
myelinates PNS in a 1:1 ratio;
promotes axonal regeneration;
Derived from neural crest;
destroyed in Guillain-Barre;
Acoustic neuroma
type of schwannoma;
Typically located in internal acoustic meatus (CN 8);
If bilateral think NF2 (on gene 22, affecting 2 ears)
Sensory: Free nerve endings
C fibers: slow unmyelinated fibers;
A delta fibers: fast, myelinated fibers;
Located on all skin;
conveys pain and temperature
Sensory: Meissner corpuscles
Large, myelinated, and adapt quickly;
Found in glabrous (hairless) skin;
Senses dynamic, fine/light touch and position sense
Sensory: Pacinian corpuscles
Large, myelinated and adapt quickly;
Found in Deep skin layers, ligaments, and joints;
Senses vibration and pressure sensation
Sensory Merkel discs
Large, myelinated and adapt slowly;
Found in the basal epidermal layer and in hair follicles;
Sense pressure, deep static touch (e.g. shapes, edges), and position sense
What are the different layers/parts to a peripheral nerve and important info about them
Endoneurium- invests single nerve fiber layers (inflammatory infiltrate in guillain Barre syndrome);
Perineurium (permeability barrier)- surrounds a fascicle of nerve fibers, must be rejoined in microsurgery for limb reattachment;
Epineurium- dense connective tissue that surrounds entire nerve (fascicle and bleed vessels)
Ependymal cells
Line ventricles of brain;
some differentiate into choroid epithelial cells;
cilia assist in CSF circulation
Tanycytes
Specialized type of ependymal cells;
basal cytoplasmic processes contact CNS blood;
thought to aid in blood-CSF transport
NE: where is it made, what disorders alter its levels
Made in Locus Ceruleus in pons;
increased in anxiety;
decreased in depression
Dopamine: where is it made, what disorders alter its levels
Made in ventral tegmentum and SNc (midbrain);
increased in Huntington;
decreased in Parkinson;
Decreased in Depression
5-HT: where is it made, what disorders alter its levels
Made in Raphe nucleus (pons, medulla, midbrain);
Increased in parkinson;
decreased in anxiety;
decreased in depression
ACh: where is it made, what disorders alter its levels
Made in basal nucleus of Meynert;
Increased in Parkinson;
decreased in Alzheimer;
Decreased in Huntingtons
GABA: where is it made, what disorders alter its levels
Decreased in Anxiety;
Decreased in Huntington;
Made in nucleus Accumbens
Locus ceruleus is activated by what emotion
stress and panic
Nucleus Accumbens and septal nucleus are know for being what
the reward center, pleasure, addiction, and fear
Blood-Brain Barrier: made from
Foot process of astrocytes, tight junctions in non fenestrated capillary endothelial cells, and a Basement membrane;
Blood-Brain Barrier: what crosses it
Glucose and amino acids cross slowly via carrier mediated transport;
Nonpolar/lipid soluble cross rapidly via diffusion;
Area postrema has no BBB (vomiting center, OVLT-osmotic sensing);
Function of Hypothalamus
Hypothalamus wears TAN HATS; Thirst and water balance; Adenohypophysis control (regulates anterior pituitary), Neurohypophysis releases hormones produced in the hypothalamus; Hunger; Autonomic Regulation; Temperature Control; Sexual urges
what is the OVLT
Part of hypothalamus;
not covered by BBB;
Organum vasculosum of the lamina terminalis-senses change in osmolarity)
Area postrema responds to
responds to emetics
What nucleus makes ADH
Supraoptic nucleus
What nucleus makes oxytocin
Paraventricular nucleus
Lateral area of the hypothalamus
Hunger;
Destruction leads to anorexia and failure to thrive in kids;
Inhibited by leptin;
If you zap you lateral nucleus you shrink laterally
Ventromedial area of the hypothalamus
Satiety;
Destruction (e.g. craniopharyngioma) leads to hyperphagia;
stimulated by leptin;
If you zap your ventromedial nucleus, you grow ventrally and medially
Anterior hypothalamus
Cooling and parasympathetics;
Anterior Nucleus=Cooling off (A/C=anterior cooling)
Posterior hypothalamus
Heating, sympathetics;
Posterior nucleus=get fired up (heating and parasympathetics)
Suprachiasmatic nucleus of the hypothalamus
Circadian rhythm;
SCN releases NE on the pineal gland leading to melatonin;
SCN responds to light (or lack there of)
Rapid Eye movement in REM sleep is caused by the
PPRF paramedian Pontine Reticular Formation
Drugs that decrease REM
Alcohol, Benzodiazepines, and barbiturates all decrease REM and delta wave sleep as well;
NE also decreases REM
How do you treat enuresis
bedwetting treated with oral desmopressin acetate (DDAVP), which mimics ADH;
Preferred over imipramine due to side effects
What can treat night terrors and sleep walking
Benzodiazepines
Awake (eyes open) what is the EEG look like
Beta waves (highest frequency, lowest amplitude)
What is the EEG look like in Awake stage with eyes closed
Alpha waves
Stage N1 of sleep
light sleep, theta wave
Stage N2 of sleep
Deeper sleep;
when bruxism occurs;
Sleep spindles and K complexes
Stage N3 of sleep
Deepest sleep that is non-REM;
sleepwalking, night terrors, and bedwetting occur;
delta waves (lowest frequency, highest amplitude)
REM sleep
Loss of motor tone, increased Brain O2 usage, increase and variable pulse and blood pressure; When dreaming and penile/clitoral tumescence occur; may serve a memory processing function; Beta waves (live awake with eyes open stage)
Posterior pituitary
Receives hypothalamic axonal projections from supraoptic (ADH) and paraventricular (oxytocin) nuclei;
input, information, destination of the VPL of the thalamus
Input is the spinothalamic and dorsal column/medial lemniscus;
Info is pain and temp, pressure, touch, vibration and proprioception;
destination is the primary somatosensory cortex
input, information, destination of the VPM
Trigeminal and gustatory pathway;
info is Face sensation and taste;
destination is the primary somatosensory cortex;
Makeup goes on the FACE (vpM)
input, information, destination of the LGN
Input is CNII;
Info is vision;
destination is the Calcarine sulcus;
Lateral=Light
input, information, destination of the MGN
input is the Superior olive and inferior colliculus of tectum;
info is hearing;
Destination is the auditory cortex of the temporal lobe;
Medial=music
input, information, destination of the VL
Input is the basal ganglia and cerebellum;
Info is motor;
Destination is the Motor Cortex
Limbic system
Involved in emotion, long-term memory, olfaction, behavior modification, and autonomic nervous system function;
Structures include hippocampus, amygdala, fornix, mammillary bodies, and cingulate gyrus;
5 F’s-Feeding, Fleeing, Fighting, Feeling, Sex
Cerebellum
Aids in coordination and balance;
Control ipsilateral side (outputs go to contralateral motor cortex, then that crosses when going down the corticospinal tract)
Inputs into the Cerebellum
Contralateral cortex via the middle cerebellar peduncle;
Ipsilateral proprioceptive information via inferior cerebellar peduncle from the spinal cord (inputs nerves=climbing and mossy fibers)
Outputs from the Cerebellum
Sends info to contralateral vortex to modulate movement;
Output is the purkinje cells to the deep nuclei of the cerebellum to the contralateral cortex via the superior cerebellar peduncle;
What are the deep nuclei of the Cerebellum
Lateral to medial they are the Dentate, Emboliform, Globose, Fastigial (don’t eat greasy foods);
Lateral lesions in the Cerebellum
Voluntary movement of the extremities;
when injured, you tend to fall toward injured (ipsilateral) side
Medial lesions in the cerebellum
Lesions involve midline structures (vermal cortex, fastigial nuclei) and/or the flocculonodular lobe result in truncal ataxia, nystagmus, and head tilting;
These patients also may have a wide-based gait and deficits in truncal coordination;
Usually midline lesions result in bilateral motor deficits in axial and proximal limb muscles
What does dopamine do in the basal ganglia
Binds D1 in the excitatory pathway, and to D2 in the inhibitory pathway which leads to increased motion
Parkinson Disease
Degenerative disorder of CNS associated with Lewy Bodies (composed of alpha-synuclein- intracellular eosinophilic inclusion) and loss of dopaminergic neurons (i.e. depigmentation) of the substantia nigra pars compacta
Huntington Disease
Autosomal dominant trinucleotide repeat (CAG) disorder on chromosome 4;
symptoms manifest between 20 and 40;
Choreiform movements, aggression, depression, dementia;
Decreased levels of GABA and ACh in the brain;
Neuronal death via NMDA-R binding and glutamate toxicity;
Atrophy of the caudate nuclie can be seen on imaging;
CAG=Caudate loses Ach and Gaba
Hemiballismus
Sudden, wild flailing of 1 arm with or without leg;
Contralateral subthalamic nucleus injury (e.g. lacunar infarct);
Chorea
Sudden, jerky, purposeless movements;
Lesion in the basal ganglia (think Huntington)
Athetosis
Slow, writhing movements, especially seen in fingers;
lesion to the basal ganglia (think Huntington)
Myoclonus
Sudden, brief, uncontrolled muscle contraction;
Jerks, hiccups;
Common in metabolic abnormalities such as renal and liver failure
Dystonia
Sustained, involuntary muscle contractions;
Writer’s cramp;
blepharospasm (sustained eyelid twitch)
Essential tremor
Action tremor; exacerbated by holding posture/limb position;
Genetic predisposition;
Patients often self-medicated with EtOH, which decreases tremor amplitude;
Treat using beta blockers, primidone
Resting tremor
Uncontrolled movement of distal appendages (most noticeable in hands);
tremor goes away with purposeful movement;
Think Parkinson disease;
Intention tremor
Slow, zigzag motion when pointing/extending arm towards target;
Cerebellar dysfunction
Internal Capsule: what are the 3 areas and what 3 tracts go through each
Anterior Limb that carries the Frontopontine and thalamicortico fibers;
Genu which carries the Corticobulbar fibers;
Posterior limb which carries the Corticospinal and some corticobulbar tracts
Lesion to the amygdala
Kluver-Bucy Syndrome (hyperorality, hypersexuality, disinhibited behavior);
Associated with HSV-1 infection
Lesion to the Frontal lobe
Disinhibition and deficits in concentration, orientation, and judgment;
May have reemergence of primitive reflexes
Lesion to the Right parietal-temporal cortex
Spatial neglect syndrome (agnosia of the contralateral side of the world);
This is the non-dominant side in most people
Lesion to the left parietal-temporal cortex
Agraphia, acalculia, finger agnosia, and left-right disorientation;
Called Gerstmann syndrome
Lesion to the Reticular activating system
found in the midbrain;
Reduced levels of arousal and wakefullness (e.g. coma)
Lesion to the Mammilary bodies
Wernicke-Korsakoff syndrome;
Confusion, opthalmoplegia, ataxia;
memory loss (anterograde and retrograde amnesia), confabulation, personality changes;
associated with thiamine B1 deficiency, EtOH abuse;
can be precipitated by giving glucose to a B1 deficient patient;
Wernicke likes a CAN of beer (Confusion, Ataxia, Nystagmus)
Lesion to the basal ganglia
May result in tremor at rest, chorea, or athetosis;
Think Parkinson
Lesion to the Cerebellar hemispheres
Intention tremor, limb ataxia, and loss of balance;
damage to the cerebellum leads to ipsilateral deficits;
Fall toward side of lesion;
Cerebellar hemispheres are lateral and affect lateral limbs
Lesion to the cerebellar vermis
Truncal ataxia;
Dysarthria;
Vermis is medial so it affects medial structures
Lesion to the Subthalamic nucleus
Get a contralateral hemiballismus
Lesion to the bilateral hippocampus
Anterograde amnesia-inability to make new memories
Lesion to the Paramedian Pontine Reticular Formation
Eyes look away from side of lesion
Lesion to the Frontal Eye Fields
Eyes look toward the side of lesion
Lesion to the temporo-occipital association cortex
Get visual agnosia (see an object, but you can’t recognize it)
Central Pontine Myelinolysis
A variant of osmotic demyelination syndrome;
Acute paralysis, dysarthria, dysphagia, diplopia, and loss of consciousness;
Can cause locked in syndrome;
Massive axonal demyelination in pontine white matter tracts secondary to osmotic forces and edema;
Usually caused by overly rapid correction of hyponatremia;
From low to high you pons will die, from high to low your brain will blow (cerebellar edema/herniation)
Aphasia
Higher order inability to speak
Dysarthria
motor inability to speak
Broca aphasia
non-fluent aphasia with intact comprehension;
broca area is in the inferior frontal gyrus of frontal lobe;
Broca Broken Boca (mouth in spanish)
Wernicke aphasia
Fluent aphasia with impaired comprehension and repetition;
Wernicke area is in the superior temporal gyrus of temporal lobe;
Wernicke is Wordy by makes no sense
Global aphasia
Non-fluent with impaired comprehension;
both broca and wernicke areas affected
Conduction aphasia
Poor repetition but fluent speech and intact comprehension;
Can be caused by damage to the superior temporal gyrus and/or left supramarginal gyrus;
Can’t repeat phrases
Transcortical motor aphasia
Non-fluent aphasia with good comprehension and repetition
Transcortical sensory aphasia
Poor comprehension with fluent speech and repetition
Mixed transcortical aphasia
non-fluent speech, poor comprehension, good repetition
Middle Cerebral Artery lesions can affect what areas
Motor cortex (contralateral upper limb and face paralysis); Sensory cortex (contralateral loss of sensation of upper and lower limbs and face); Temporal lobe (Wernicke and Broca; See aphasia if dominant side (left), See hemineglect if lesion is nondominant (right) side)
Anterior Cerebral Artery lesion can affect what areas
Motor cortex (lower limb contralateral paralysis); Sensory Cortex (Contralateral lower limb loss of sensation)
Lenticulo-Striate Artery lesion can affect what areas
Striatum and internal capsule (contralateral hemiparesis/hemiplegia)
Anterior spinal artery lesion can affect what areas
Lateral corticospinal tract (contralateral hemiparesis of upper and lower limbs; Medial lemniscus (decreased contralateral proprioception); Caudal medulla/hypoglossal nerve (ipsilateral hypoglossal dysfunction and tongue deviates ipsilaterally)
Medial Medullary Syndrome
Caused by infarct of paramedian branches of the ASA and vertebral arteries;
Posterior Inferior Cerebellar Artery lesion affects what areas
Lateral Medullary (Wallenberg) syndrome
Lateral medulla;
Vestibular nuclei (vomiting, vertigo, nystagmus);
Lateral spinothalamic and spinal trigeminal nucleus (decreased pain and temp from ipsilateral face and contralateral body);
Nucleus ambiguus (dysphagia, hoarsenss, decreased gag reflex);
Sympathetic fibers (ipsilateral horners syndrome);
Inferior cerebellar peduncle (ataxia, dysmetria)
Anterior inferior Cerebellar artery lesion affects what areas
Lateral pontine syndrome;
Facial nucleus are specific to AICA;
Lateral pons, cranial nerve nuclei, vestibular nuclei, facial nucleus, spinal trigeminal nucleus, cochlear nuclei, sympathetic fibers;
Symptoms are vomiting, vertigo, nystagmus, Paralysis of the face, decreased lacrimation and salvation, decreased taste from ant. 2/3 tongue, decreased corneal reflex, decreased facial pain and temp, ipsilateral decreased hearing, ipsilateral horners ,ataxia and dysmetria
Posterior Cerebral Artery lesion affects what
Occipital cortex and visual cortex;
contralateral hemianopia with macular sparing (visual acuity is fine, but decreased visual field)
Basilar artery lesion affects what areas
Pons, medulla, lower midbrain, corticospinal and corticobulbar tracts, ocular cranial nerve nuclei, PPRF;
Symptoms are preserved consciousness and blinking with quadraplegia, loss of voluntary facial, mouth, and tongue movements (locked in syndrome where you can do vertical eye movements and blink)
Anterior Communicating artery lesion
Most common lesion in aneurysm;
can lead to stroke;
Saccular (berry) aneurysm can impinge cranial nerves;
Symptoms are visual field defects;
Lesions are typically aneurysms not strokes!
Posterior Communicating artery lesions
Common site for saccular aneurysms;
CN III palsy where eye is down and out with ptosis and pupil dilation;
Lesions are typically aneurysms not strokes!
Berry Aneurysms
Occur at bifurcations in the circle of willis;
Mostly at the junction of the Acom and ACA;
Rupture leads to subarachnoid hemorrhage (worst headache ever) or hemorrhagic stroke;
can compress optic chiasm;
Associated with ADPKD, Ehlers-Danlos, Marfan;
Risk factors are old age, HTN, smoking, being black
Charcot-Bouchard microaneurysm
Associated with chronic HTN;
affects small vessels (mostly basal ganglia and thalamus)
Central post stroke pain syndrome
Neuropathic pain due to thalamic lesions;
Initial sensation of numbness and tingling followed by weeks to months of allodynia (normal stimuli cause pain) and dysaesthesia;
occurs in 10% of stroke patients
Epidural Hematoma
Rupture of the middle meningeal artery (branch of the maxillary artery), often secondary to fracture of the temporal bone;
Lucid Interval;
Rapid expansion of blood since it is arterial leading to transtentorial herniation and CN III palsy;
CT shows lens like lesions, hyperdense blood collection that does NOT cross suture lines (Can cross falx, tentorium)
Subdural Hematoma
Snaking Subdural;
Rupture of bridging veins;
slow venous bleeding so it takes longer;
seen in elderly individuals, alcoholics, blunt trauma, shaken baby;
Can cross suture lines but cannot cross falx or tentorium
Subarachnoid hemorrhage
Rupture of an aneurysm or an AVM;
rapid time course;
Patient complains of worst headache of my life;
bloody or yellow (xanthochromic) spinal tap;
2-3 days afterward, risk of vasospasm due to blood breakdown (not visible on CT, treat with nimodipine) and rebleeding (seen on CT)
Intraparenchymal hemorrhage
AKA Hypertensive hemorrhage;
Most commonly caused by systemic HTN;
Also seen with amyloid angiopathy, vasculitis, and neoplasm;
Typically occurs in the basal ganglia and internal capsule (charcot-bouchard aneurysm of lenticulostriate vessels), but can be lobar
What is the time table of histologic events after a ischemic stroke
12-48 hours you get Red neurons;
24-72 hours you get necrosis + neutrophils;
3-5 days you get macrophages;
1-2 weeks you get reactive gliosis + vascular proliferation;
>2 weeks you get glial scars
Ischemic stroke: what areas are susceptible to damage
irreversible damage starts at 5 minutes;
most vulnerable areas are the hippocampus, neocortex, cerebellum, watershed areas;
Hemorrhagic stroke
Intracerebral bleeding, often due to HTN, anticoagulation, and cancer (abnormal vessels can bleed);
may be secondary to ischemic stroke followed by reperfusion (increased vessel fragility);
Basal ganglia are most common site of intracerebral hemorrhage
Ischemic Stroke: what is it
Acute blockage of vessels leading to disruption of blood flow causing ischemia;
results in liquefactive necrosis;
How do you treat ischemic strokes
Treatment- tPA (if within 3 to 4.5 hr of onset and no hemorrhage/risk of hemorrhage). Reduced risk with medical therapy (e.g. aspirin, clopidogrel)
What are the types of ischemic strokes
1) Thrombotic-due to a clot forming directly at the site of infarct (commonly at MCA);
2) Embolic-an embolus from another part of the body obstructs a vessel, can affect multiple vascular territories, often cardioembolic;
3) Hypoxic-due to hypoperfusion or hypoxemia, common during cardiovascular surgery, tends to affect watershed areas;
Transient ischemic attacks
Brief, reversible episode of focal neurologic dysfunction
Ventricular system: the flow of CSF
Lateral ventricle dumps into the 3rd ventricle via right and left interventricular foramina of Monro;
3rd vent. dumps into 4th vent via cerebral aqueduct of Sylvius;
4th dumps in to subarachnoid space via 2 foramina of Luschka (Lateral) and 1 foramen of Magendie=Medial;
How is CSF made and reabsorbed
Made by the ependymal cells of the choroid plexus;
reabsorbed by arachnoid granulations in the superior sagittal sinus
Communicating Hydrocephalus
decreased CSF absorption by arachnoid granulations, which can lead to increased intracranial pressure, papilledema, and herniation (e.g. arachnoid scarring post meningitis)
Normal pressure hydrocephalus
Does not result in increased subarachnoid space volume;
Expansion of ventricles distorts the fibers of the corona radiata and leads to clinical triad of urinary incontinence, ataxia, and cognitive dysfunction (wet, wobbly, and wacky);
treat with ventricle shunt
Hydrocephalus ex vacuo
Appearance of increased CSF in atrophy (Alz, advanced HIV, Huntington, Pick disease);
Intracranial pressure is normal;
triad not seen;
Apparent increase in CSF observed in imaging is actually result of decreased neural tissue due to atrophy
Noncommunicating hydrocephalus
Caused by structural blockage of CSF circulating within the ventricular system (e.g. stenosis of the aqueduct of Sylvius) leading to increased intracranial pressure leading to bilateral papilladema, nausea/vomiting, nuchal rigidity, mental status change
How many spinal nerves do we have
31 spinal nerves;
8 cervical, 12 thoracic, 5 lumbar, 5 sacral, 1 coccygeal;
C1-C7 exit at corresponding vertebra, all others go out one vertebra below
Vertebral disc herniation
Nucleus pulposus (soft central disc) herniates though the annulus fibrosus (outer ring); usually occurs posterolaterally at L4-L5 or L5-S1
Dorsal column sense what
sends ascending pressure, vibration, fine touch, and proprioception;
Dorsal column first order neurons
1st order neurons: sensory nerve endings to the cell bodies in the dorsal root ganglia, enters the spinal cord, ascends ipsilaterally in dorsal column;
1st synapse: ipsilateral cuneatus (upper body, arms) or gracilis (lower body, legs) in medulla
Dorsal column second and third order neurons
from ipsilateral cuneatus (upper body, arms) or gracilis (lower body, legs) it decussates in medulla then ascends contralaterally in medial lemniscus;
second synapse is in the VPL of the thalamus;
3rd order neuron goes to sensory cortex
Spinothalamic tract: senses what
Sends ascending-lateral: pain, tempurature and medial: crude touch and pressure;
Spinothalamic tract: 1st order neurons
1st order neurons are sensory nerve endings (Adelta and C fibers) to the cell body in dorsal root ganglia where it enters the spinal cord;
1 synapse is in the ipsilateral gray matter of the spinal cord (dorsal horn)
Spinothalamic tract: 2nd order neurons
from the synapse in the ipsilateral dorsal horn the 2nd order neuron decussates at the anterior white commissure and ascends contralaterally to the VPL thalamus where it synapses and a 3rd order neuron goes to the sensory cortex
Lateral corticospinal tract: sends what
Sends descending voluntary movement of contralateral limbs
Lateral corticospinal tract: first order neurons
UMN: cell body in primary motor cortex where it descends ipsilaterally (through internal capsule), most fibers decussate at caudal medulla (pyramidal decussation) where it descends contralaterally;
First synapse is in the cell body of the anterior horn in the spinal cord
Lateral corticospinal tract: second order neurons
from the anterior horn the LMN (2nd order) leaves the spinal cord and goes to the NMJ
Romberg test looks at what
unconscious proprioception;
tests the spinocerebellar and dorsal column pathways
Multiple sclerosis is destruction of what in the spinal cord
Due to demyelination;
mostly white matter of cervical region;
random and asymmetric lesions, due to demyelination;
scanning speech, intention tremor, nystagmus
Amyotrophic lateral sclerosis: is damage to what
Combined UMN and LMN deficits with NO sensory, cognitive, or oculomotor deficits;
Can be caused by defect in superoxide dismutase 1;
Commonly presents as fasciculations with eventual atrophy and weakness of hands;
fatal;
RiLUzole (Lou Gerhrig) is given to decrease presynaptic glutamate release;
Complete occlusion of the anterior spinal artery damages what parts of the spinal cord
Spares the dorsal columns and lissauer tract;
Every other tract is lesioned at and below the area of the occlusion;
The upper thoracic ASA territory is a watershed area, as artery of Adamkiewicz supplies ASA below T8
Tabes dorsalis affects what
Caused by tertiary syphilis;
Results from degeneration (demyelination) of dorsal columns and roots leading to impaired sensation and proprioception and progressive sensory ataxia leading to poor coordination;
associated with Charcot joints, shooting pain, Argyll Robertson pupils;
See absent DTRs and + romberg
Syringomyelia
Syrinx expands and damages anterior white commissure of spinothalamic tract (2nd order neurons) leading to bilateral loss of pain and temp sensation (usually C8 to T1);
Seen with Chiari 1 malformations;
can expand and affect other tracts
Vitamin B12 or Vitamin E deficiency leads to problems with what parts of the spinal cord
Get subacute combined degeneration which is demyelination of dorsal columns, lateral corticospinal tracts, and spinocerebellar tracts;
see ataxic gate, paresthesia, impaired position and vibration sense
Poliomyelitis;
Cause by polio virus (Fecal-oral);
replicates in the oropharynx and small intestine before spreading via blood to the CNS;
Infection causes destruction of cells in the anterior horn of the spinal cord (death of LMNs);
Symptoms are LMN signs and general infection signs;
Findings: CSF with increased WBCs and slight increase of protein (no glucose change);
Virus can be found in stool or throat;
Werdnig Hoffmann Disease
AKA spinal muscular atrophy;
Congenital degeneration of the anterior horns of the spinal cord leading to LMN lesions;
Floppy baby with marked hypotonia and tongue fasciculations, starts eating then gets tired;
infantile type has median age of death of 7 months (corticobulbar tract damage leads to respiratory failure);
Autosomal recessive
Friedreich Ataxia
Autosomal recessive trinucleotide repeat disorder (GAA) on chromosome 9 in gene that encodes frataxin (iron binding protein);
leads to impairment in mitochondrial function;
degeneration of multiple spinal tracts leads to muscle weakness and loss of DTRs, vibratory sense, proprioception;
Friedreich is Fratastic (frataxin): he is your favorite FRAT brother, always STUMBLING, STAGGERING, and FALLING, but has a big heart (hypertrophic cardiomyopathy cause of death);
Present in child with kyphoscoliosis
Brown Sequard syndrome
Hemisection of spinal cord;
Ipsilateral UMN signs below level of the lesion (corticospinal damage);
Ipsilateral loss of tactile, vibration, proprioception sense 1-2 levels below lesion (dorsal column damage);
Contralateral pain and temp loss below level of lesion (spinothalamic damage);
Ipsilateral loss of all sensation at level of lesion;
Ipsilateral LMN at level of lesion;
If at level T1 will get Horners due to damage of the oculosympathetic pathway
Horner Syndrome
Sympathectomy of face;
Ptosis (slightly drooping eyelid; superior tarsal muscle);
Anhidrosis (absent sweating) and flushing of affected side;
Miosis (pupil constriction);
Associated with lesion at T1;
PAM is horny
Track the oculosympathetic pathway
starts in hypothalamus descends with 1st neuron to the lateral horn in T1 where it synapses on 2nd order;
2nd order leaves spinal cord and goes to sympathetic chain where it rises to C2 (at bifercation of common carotid) and synapses on 3rd order;
Exits at C2 and innervation of sweat tracts with the external carotid and innervation of eye tracts the internal carotid
Notable Dermatomes
C2 is back of head (skull cap) but not face;
C3 is the turtleneck;
C4 is the low collar shirt;
T4 is nipples;
T7 is the xiphoid process;
T10 is the umbilicus;
L1 is inguinal ligament;
L4 wraps lateral thigh and covers knee cap;
S2, 3, 4; erection and sensation of penile and anal zones
Clinical Reflexes
Biceps=C5; Triceps=C7; Patella=L4; Achilles=S1; Cremaster reflex=L1, L2; Anal wink=S3, S4
Moro reflex
Hang on for life reflex;
abduct/extend limbs when startled, and then draw together
Rooting reflex
Movement of head toward one side if cheek or mouth is stroked;
nipple seeking
Sucking reflex
sucking response when roof of mouth is touched
Palmar reflex
Curling of fingers if palm is stroked
Galant reflex
Stroking along one side of the spine while newborn is face down;
causes lateral flexion of lower body toward stimulated side
Pineal gland function
Melatonin release;
Circadian rhythms
Superior colliculi
Conjugate vertical gaze center;
Remember that your eyes are SUPERIOR to your ears
Inferior Colliculi
Auditory;
Remember that your eyes are SUPERIOR to your ears
Parinaud syndrome
Paralysis of conjugate vertical gaze due to lesion in superior colliculi (e.g. pinealoma)
CN III does what
Oculomotor nerve; Eye movement; pupillary constriction (sphincter pupillae: Edinger-Westphal nucleus, muscarinic receptors); Accommodation, Eyelid opening (levator palpebrae)
Cranial nerve reflexes: Corneal reflex
Afferent: V1 ophthalmic (nasociliary branch);
Efferent: VII (temporal branch: orbicularis oculi)
Cranial nerve reflexes: Lacrimation
Afferent is the V1 (loss of reflex does not preclude emotional tears);
Efferent: VII
Cranial nerve reflexes: Jaw Jerk
Afferent is V3 (sensory- muscle spindle from masseter);
Efferent is V3 (motor-masseter)
Cranial nerve reflexes: Pupillary
Afferent is II;
Efferent is III
Cranial nerve reflexes: Gag
Afferent is IX (ipsilateral);
Efferent is X (bilateral)
CN VII innervates what muscles
Facial movement;
Orbicularis oculi (eye closing);
Stapedius of ear
What muscles doe CN IX innervate
Swallowing, Stylopharyngeus (elevates pharynx, larynx)
Nucleus Solitaris
Visceral Sensory information which is taste, baroreceptors and gut distention;
Sensory=Solitaris
CN VII, IX, and X
Nucleus Ambiguus
Motor innervation of pharynx, larynx, and upper esophagus (e.g. swallowing, palate elevation);
CN IX, X, XI (cranial portion);
aMbiguus=Motor
Dorsal motor nucleus
Sends autonomic (parasympathetic) fibers to heart, lungs, and upper GI; CN X
How does this structure exit the Skull: CN I
cribiform plate
How does this structure exit the Skull: CN II
Through sphenoid bone (optic canal)
How does this structure exit the Skull: ophthalmic artery
Through sphenoid bone (optic canal)
How does this structure exit the Skull: Central retinal vein
Through sphenoid bone (optic canal)
How does this structure exit the Skull: CN III
Superior Orbital fissure of the sphenoid bone
How does this structure exit the Skull: CN IV
Superior Orbital fissure of the sphenoid bone
How does this structure exit the Skull: V1
Superior Orbital fissure of the sphenoid bone
How does this structure exit the Skull: VI
Superior Orbital fissure of the sphenoid bone
How does this structure exit the Skull: ophthalamic vein
Superior Orbital fissure of the sphenoid bone
How does this structure exit the Skull: parasympathetic fibers
Superior Orbital fissure of the sphenoid bone
How does this structure exit the Skull: CN V2
Foramen Rotundum in the sphenoid bone
How does this structure exit the Skull: CN V3
Foramen Ovale in the sphenoid bone
How does this structure exit the Skull: Middle Meningeal Artery
Foramen spinosum in the sphenoid bone
How does this structure exit the Skull: CN VII
Internal acoustic meatus
How does this structure exit the Skull: CN VIII
Internal acoustic meatus
How does this structure exit the Skull: CN IX
Jugular Foramen
How does this structure exit the Skull: CN X
Jugular Foramen
How does this structure exit the Skull: CN XI
Jugular Foramen
How does this structure exit the Skull: Jugular Vein
Jugular Foramen
How does this structure exit the Skull: CN XII
Hypoglossal Canal
How does this structure exit the Skull: Spinal roots of XI
Foramen magnum
How does this structure exit the Skull: Vertebral Arteries
Foramen Magnum
What Passes through this structure: Optic Canal
CN II, ophthalamic artery, central retinal vein
What Passes through this structure: Superior Orbital Fissure
CN III, CN IV, V1, VI, ophthalmic vein, sympathetic fibers
What Passes through this structure: Foramen Rotundum
CN V2
What Passes through this structure: Foramen Ovale
CN V3
What Passes through this structure: Foramen spinosum
Middle Meningeal artery
What Passes through this structure: Internal Auditory Meatus
CN VII, VIII
What Passes through this structure: Jugular Foramen
CN IX, X, XI, Jugular Vein
What Passes through this structure: Hypoglossal Canal
CN XII
What Passes through this structure: Foramen Magnum
Spinal roots of CN XI, Brain stem, vertebral arteries
Cavernous Sinus
A collection of venous sinuses on either side of the pituitary;
blood from eye and superficial cortex drains to the cavernous sinus and then into the internal jugular vein
Cavernous Sinus: what is it in
CN III, IV, V1, V2 and VI and postganglionic sympathetic fibers en route to the orbit all pass through the cavernous sinus;
Cavernous portion of internal carotid artery is also here;
Think of it as the nerves of eye movement plus V1 and V2
Cavernous sinus syndrome
Due to mass effect, fistula, thrombosis;
ophthalmoplegia and decreased corneal and maxillary sensation with normal visual acuity;
CN VI commonly affected
CN V motor lesion
Jaw deviates toward side of lesion due to unopposed force from the opposite pterygoid muscle
CN X lesion
Uvula deviates away from side of lesion;
weak side collapses and uvula points away
CN IX lesion
Weakness turning head to contralateral side of lesion (SCM);
Shoulder droop on side of lesion (trapezius);
The left SCM contracts to help turn the head to the right
CN XII lesion (LMN)
Tongue deviates toward side of lesion (“lick your wounds”) due to weakened tongue muscles on the affected side
Bones of middle ear
Malleus, incus, and stapes
Inner ear
Snail shaped, fluid filled cochlea;
contains basilar membrane that vibrates secondary to sound waves;
Vibration transduced via specialized hair cells to the auditory nerve signaling to the brainstem;
low frequency is heard at apex near helicotrema (wide, flexible);
High frequency heard best at base of cochlea (thin, rigid)
Rinne and Weber test for Conductive hearing loss
Rinne test is abnormal (bone > air);
Weber Test localized to the affected side
Rinne and Weber test for Sensorineural hearing loss
Normal Rinne test (Air > Bone);
Weber test localizes to unaffected ear
Noise-induced hearing loss
Damage to sterocilliated cells in organ of Corti;
Loss of high frequency hearing 1st;
Sudden extremely loud noises can produce hearing loss die to tympanic membrane rupture
Facial Lesions: UMN lesion
Lesion of motor cortex or connection between cortex and facial nucleus;
Contralateral paralysis of lower face;
Forehead spared due to bilateral UMN innervation
Facial Lesions: LMN lesion
Ipsilateral paralysis of upper and lower face
Facial Lesions: Facial nerve palsy
Complete destruction of the facial nucleus itself or its branchial efferent fibers (facial nerve proper);
Peripheral ipsilateral facial paralysis (drooping smile) with inability to close eye on affected side;
Can occur idiopathically, or with lyme disease, herpes simplex, herpes zoster, sarcoidosis, tumors and diabetes;
Treatment includes corticosteroids
Mastication muscles
3 muscles Masseter, teMporals, Medial pterygoid;
1 opens the mouth-Lateral Pterygoid;
All innervated by V3;
M’s Munch and Lateral Lowers
Hyperopia
Eye too short for refractive power of cornea;
Light focused behind the retina;
Farsightedness
Myopia
Eye too long for refractive power of cornea and lens leading to the light focusing in front of retina;
Nearsightedness
Astigmatism
Abnormal curvature of cornea resulting in different refractive power at different axes;
Presbyopia
Decrease in focusing ability during accommodation due to sclerosis and decreased elasticity
Uveitis
Inflammation of anterior uvea and iris, with hypopyon (sterile pus), accompanied by conjuctival redness;
Often associated with systemic inflammatory disorders (sarcoid, RA, Juvenile idiopathic arthritis, TB, HLA-B27 PAIR disorders)
Retinitis
Retinal edema and necrosis leading to scar;
often viral (CMV, HSC, HZV);
associated with immunosuppression
Central retinal artery occlusion
Acute, painless, monocular vision loss;
Retina cloudy with attenuated vessels and cherry-red spot at fovea
Retinal vein occlusion
Blockage of central or branch retinal vein due to compression from nearby arterial atherosclerosis;
Retinal hemorrhage and edema in affected area
Diabetic retinopathy: pathophysiology
Non-proliferative: damaged capillaries leak blood so lipids and fluid seep into retina and you see hemorrhages and macular edema (treat with macular laser and better glucose control);
Proliferative is chronic hypoxia results in new blood vessel formation with resultant traction on retina (treat with anti-VEGF injections)
Glaucoma
Optic disc atrophy with characteristic cupping, usually with increased intraocular pressure and progressive peripheral visual field loss
Open angle glaucoma
Associated with increased age, African American race, family history;
Painless, more common in U.S.;
Primary- Cause unclear;
Secondary- Blocked trabecular meshwork from WBC (e.g. uveitis), RBCs (vitreous hemorrhage), retinal elements (e.g. retinal detachment
Closed/Narrow angle glaucoma
Primary- enlargement or forward movement of lens against central iris (pupil margin) leads to obstruction of normal aqueous flow through pupil so fluid builds up behind iris, pushing peripheral iris against cornea and impeding flow through trabecular meshwork;
Secondary- hypoxia from retinal disease (e.g., diabetes, vein occlusion) induces vasoproliferation in iris that contracts angle;
Chronic closure of glaucoma
often asypmtomatic with damage to optic nerve and peripheral vision
Acute angle closure of glaucoma
true ophthalmic emergency;
increased IOP pushes iris forward causing angle to close abruptly;
very painful, sudden vision loss, halos around lights, rock hard eye, frontal headache;
do not give epinephrine because of its mydriatic effect
Cataract
Painless, often bilateral, opacification of lens leading to decreased vision;
Risk factors are increased age, smoking, EtOH, excessive sunlight, prolonged corticosteroid use, classic galactosemia, galactokinase deficiency, diabetes (sorbital), trauma, and infections
Papilledema
optic disc swelling (usually bilateral) due to increased ICP;
enlarged blind spot and elevated optic disc with blurred margins seen on fundoscopic exam
CN IV damage
motor to superior oblique;
patient’s eye moves upward, particularly with contralateral gaze and head tilt toward the side of the lesion (problems going down stairs, may present with compensatory head tilt in the opposite direction)
Miosis
constriction, parasympathetic;
1st neuron: Edinger Westphal nucleus to ciliary ganglion via CN III;
2nd Neuron: short ciliary nerves to pupillary sphincter muscles;
Mydriasis
Dilation, sympathetic;
1st neuron: hypothalamus to ciliospinal center of Budge (C8-T2);
2nd neuron: exit at T1 to superior cervical ganglion (travels along cervical sympathetic chain near lung apex, subclavian vessels;
3rd neuron: plexus along internal carotid, through cavernous sinus: enters orbit as long ciliary nerve to pupillary dilator muscles
Pupillary light reflex
Light in either retina travels via CN II to pretectal nucleus in midbrain that activates bilaterally the Edinger-Westphal nuclei;
Pupils contract bilaterally;
So light in one eye causes both eyes to constrict
Marcus Gunn Pupil
Afferent pupillary defect due to optic nerve damage or severe retinal injury;
decreased bilateral pupillary constriction when light is shone in affected eye relative to unaffected eye;
Tested via swinging light reflex
Damage to CN III: what areas are affected first
outer layer of CN III is parasympathetic;
Inner layer is Motor;
so vascular disease that cuts off oxygen affects motor, and compression first hurts parasympathetic (think aneurysm, uncal herniation)
Retinal detachment
separation of neurosensory layer of retina (photoreceptors layer with rods and cones) from outermost pigmented epithelium (normally shields excess light, supports retina) leading to degeneration of photoreceptors leading to vision loss;
May be secondary to retinal breaks, diabetic traction, inflammatory effusions;
Often Preceded by posterior vitreous detachment (flashes and floaters) and eventual monocular loss of vision
Age related macular degeneration
Degeneration of macula (central area of retina);
causes distortion (metamorphopsia) and eventual loss of central vision;
Dry (nonexudative, 80%)- deposition of yellowish extracellular material in and beneath Bruch membrane and retinal pigment epithelium (drusen) with gradual decrease in vision, give antioxidants and multivitamin;
Wet (exudative, 15%)- rapid loss of central vision due to bleeding secondary to choroidal neovascularization, Treat with anti-VEGF or laser
internuclear ophthalmoplegia (INO)
MLF is pair of tracts that allow for crosstalk between CN VI and CN III nuclei;
coordinates both eyes to move in same horizontal direction;
Highly myelinated;
Lesions seen in demyelination;
Lesions cause medial rectus on ipsilateral side to not tract, but eyes can converge (medial rectus is working)
Alzheimer disease: genetics
old folks and increased risk in down syndrome;
Genetics: early onset in APP (Chr 21), Presenilin-1 (Chr 14), presenilin-2 (Chr 1), late onset ApoE4 (Chr 19);
ApoE2 (Chr 19) is protective;
Histology of Alzheimer disease
Decreased ACh;
Extracellular beta amyloid core;
Amyloid beta synthesized by cleaving amyloid precursor protein (APP on Chr 21);
Neurofibrillary tangles are intracellular hyperphosphorylated tau protein = insoluble cytoskeletal elements, and amount correlates to degree of dementia (worst in hippocampus)’
May see amyloid angiopathy which leads to intracranial hemorrhages (parietal lobe is most common)
Frontotemporal dementia
Picks disease;
dementia, aphasia, parkinsonian aspects;
change in personality;
Spares parietal lobe and posterior 2/3 of superior temporal gyrus;
Pick bodies are spherical tau protein aggregates;
Frontotemporal atrophy leading to disinhibition, impaired judgement and personality changes
Lewy body dementia
Initially dementia and visual hallucinatinos followed by parkinsonian features;
Alpha-Synuclein defect;
increased ubiquitin is also present
Creutzfeldt-Jakob Disease
Rapidly progressive (weeks to months) dementia with myoclonus (“startle myoclonus”);
ataxia;
Spongiform cortex;
Prions (PrPc transform into PrPsc sheet (beta pleated sheets that are resistant to proteases) AKA 14-3-3 protein;
EEG shows recurrent bursts of biphasic and triphasic periodic sharp wave complexes
Multiple Sclerosis
Autoimmune inflammation and demyelination of CNS (brain and spinal cord);
Patients can present with optic neuritis (sudden loss of vision resulting in Marcus Gunn pupils) internuclear ophthalmoplegia, hemiparesis, hemisensory symptoms, or bladder/bowel incontinence;
Relapsing and remitting course;
mostly women in their 20s and 30s, most white;
Classic triad of MS
Charcot classic triad of MS;
1) Scanning speech;
2) Intention tremor;
3) Nystagmus
Multiple Sclerosis: Findings
Increased protein (IgG) in CSF;
oligoclonal bands are diagnostic;
MRI is gold standard;
Periventricular plaques (areas of oligodendrocyte loss and reactive gliosis) with destruction of axons;
Multiple white matter lesions separated in space and time
Multiple Sclerosis: Treatment
beta-interferon, immunosuppresion, natalizumab;
Symptomatic treatment for neurogenic bladder (catheterization, muscarinic antagonists), spasticity (baclofen, GABA receptor agonist), pain (opioids)
Acute inflammatory demyelinating polyradiculopathy
most common variant of Guillain-Barre syndrome;
autoimmune condition that destroys Schwann cells leading to inflammation and demyelination of peripheral nerves and motor fibers;
Results in symmetric ascending muscle weakness/paralysis beginning in lower extremities;
Facial paralysis in 50% of cases;
Autonomic function may be severely affected (e.g. cardiac irregularities, HTN, or hypotension);
Almost all patients survive;
the majority recover completely after weeks to months;
Acute inflammatory demyelinating polyradiculopathy Findings:
increased CSF protein with normal cell count (albuminocytologic dissociation);
increased protein leads to papilledema
Acute inflammatory demyelinating polyradiculopathy: associated with what
Associated with infections (campylobacter jejuni and CMV) leads to autoimmune attack of peripheral myelin due to molecular mimicry, inoculations, and stress, but no definitive link to pathogens;
Acute inflammatory demyelinating polyradiculopathy: treatment
Treatments are respiratory support, plasmapheresis, IV immune globulins
Progressive multifocal leukoencephalopathy
demyelination of CNS due due to destruction of oligodendrocytes;
associated with HC virus;
seen in 2-4% of AIDS patients (reactivation of latent viral infection);
Rapidly progressive, usually fatal;
increased risk associated with natalizumab
Acute disseminated (postinfectious) encephalomyelitis
Multifocal perivenular inflammation and demyelination after infection (commonly measles or VZV) or certain vaccinations (e.g. rabies, smallpox);
MRI shows inflamed white matter of CNS;
treat with high dose IV corticosteroids
Metachromatic leukodystrophy
autosomal recessive lysosomal storage disease, most common due to arylsulfatase A deficiency;
buildup of sulfatides leads to impaired production of myelin sheath;
findings are central and peripheral demyelinatino with ataxia, dementia;
no treatment
Charcot-Marie-Tooth disease
also known as hereditary motor and sensory neuropathy (HMSN);
group of progressive hereditary nerve disorders related to the defective production of proteins involved in the structure and function of peripheral nerves or the myelin sheath;
typically autosomal dominant inheritance pattern and associated with scoliosis and foot deformities (high or flat arches)
Krabbe disease
autosomal recessive lysosomal storage disease due to deficiency of galactocerebrosidase;
Buildup of galactocerebroside and psychosine destroys myelin sheath;
findings are peripheral neuropathy, developmental delay, optic atrophy, globoid cells
Adrenoleukodystrophy
X-linked genetic disorder typically affecting males;
Disrupts metabolism of very-long fatty acids leading to excessive buildup in nervous system, adrenal gland, and testes;
progressive disease that can lead to long-term coma/death and adrenal gland crisis
Partial (focal) seizures
Affect 1 area of the brain;
most commonly originate in medial temporal lobe;
often preceded by seizure aura;
can secondarily generalize;
Types: 1) simple partial (consciousness intact)-motor, sensory, autonomic, psychic 2) complex partial (impaired consciousness)
Generalized seizures
Diffuse;
Absence (petit mal)- 3Hz, no postictal confusion, blank stare, no muscle tone loss;
Myoclonic-quick, repetitive jerks;
Tonic-clonic (grand mal)-alternating stiffening and movement;
Atonic-“drop” seizures (falls to floor) and mistaken fainting
Cluster headaches
Unilateral;
last 15 minutes to 3 hrs;
Repetitive brief headaches, excruciating periorbital pain with lacrimation and rhinorrhea, may induce Horner syndrome, more common in males;
Treat with inhaled O2 and sumatriptan
Tension headache
bilateral and constant;
>30 min (4-6 hour);
Steady pain, no photophobia, or phonophobia, no aura;
treat with analgesics, NSAIDs, acetaminophen, amitriptyline for chronic pain
Migraine
Unilateral;
lasts 4-72 hrs;
Pulsating pain with nausea, photophobia, or phonophobia, may have aura, due to irritation of CN V, meninges, or blood vessels (release of substance P, CGRP, vasoactive peptides);
Treat active migraine with triptans, NSAIDs, and prophylactic with propranolol, topiramate, Ca channel blockers, amitriptyline
Peripheral Vertigo
more common;
inner ear etiology (e.g. semicircular canal debris, vestibular nerve infection, Meniere disease);
positional testing leads to delayed horizontal nystagmus
Central vertigo
Brain stem or cerebellar lesion (e.g. stroke affecting vestibular nuclei or posterior fossa tumor);
Findings with directional change of nystagmus, skew deviation, diplopia, dysmetria;
Positional testing leading to immediate nystagmus in any direction; may change directions;
focal neurological findings
Sturge-Weber Syndrome
Congenital, non-inherited (somatic), developmental anomaly of neural crest derivatives (mesoderm/ectoderm) due to activating mutation of GNAQ gene;
Affects small (capillary-sized) blood vessels leading to port-wine stain of the face (non-neoplastic “birthmark” in CN V1/V2 distribution);
ipsilateral leptomeningeal angioma leads to seizures/epilepsy;
intellectual disability;
and episcleral hemangioma leading to increased IOP leading to early onset glaucoma;
Tuberous Sclerosis:
HAMARTOMAS: Hamartomas in CNS and skin; Angiofibromas; Mitral regurgitation; Ash-leaf spots; cardiac Rhabdomyoma; Tuberous sclerosis; autosomal dOminant; Mental retardation; renal Angiomyolipoma; Seizures and Shagreen patches; increased incidence of subependymal astrocytomas and ungual fibromas
Neurofibromatosis type 1 (von Recklinghausen disease)
Cafe-au-lait spots, Lisch nodules (pigmented iris hamartomas), neurofibromas in skin, optic gliomas, pheochromocytomas;
mutated NF1 tumor suppressor gene (neurofibromas, a negative regulator of Ras) on chromosome 17;
skin tumors of NF-1 are derived from neural crest cells
von-hippel-Lindau disease
VHL= chromosome 3;
Cavernous hemangiomas in skin, mucosa, organs;
bilateral renall cell carcinomas;
hemangioblastoma (high vascularity with hyperchromatic nuclei) in retina, brain stem, cerbellum, and pheochromocytomas;
autosomal dominant;
mutated VHL tumor suppressor gene on chromosome 3, which results in constitutive expression of HIF (transcription factor) and activation of angiogenic growth factors
Astrocytoma or gliobastoma multiforme
Adult tumor;
Common in adult, highly malignant primary brain tumor ~1 year median survival;
found in cerebral hemispheres;
can cross corpus callosum (butterfly glioma);
stain astrocytes for GFAP;
Pseudopalisading pleomorphic tumor cells-border central areas of necrosis and hemorrhage
Meningioma
Adult tumor;
Most common benign, second most common brain tumor;
most often occurs in convexities of hemispheres (near surface of brain) and parasagittal region;
arises from arachnoid cells, is extra-axial (external to brain parenchyma), and may have a dural attachment (tail);
often asymptomatic;
may present with seizures or focal neurological signs;
resection and/or radiosurgery;
spindle cells concentrically arranged in a whorled pattern;
psammoma bodies (laminated calcifications);
has estrogen receptors and can grow during pregnancy;
Hemangiobalstoma
adult tumor;
most often cerebellar;
associated with von hippel-lindau syndrome when found with retinal angiomas;
can produce erythropoietin leading to secondary polycythemia;
Closely arranged, thin-walled capillaries with minimal interleaving parenchyma
Schwannoma
Adult tumor;
usually found at cerebellopontine angle;
schwann cell origin;
s-100 positive;
often localized to CN VIII leading to acoustic schwannoma (aka acoustic neuroma);
resectable or treated with stereotactic radiosurgery;
bilateral acoustic schwannomas found in NF-2;
Oligodendroglioma
Adult, relatively rare, slow growing; most often in frontal lobes; chicken-wire capillary pattern; oligodendrocytes=fried egg cells (round nuclei with clear cytoplasm); often calcified in oligodendroglioma; surgically remove but may return
Pituitary adenoma
Adult cancer
most commonly prolactinoma;
bitemporal hemianopia due to pressure on optic chiasm;
hyper or hypo pituitarism are sequelae;
Pilocytic astrocytoma
usually well circumscribed;
Children, most often found in posterior fossa (e.g. cerebellum);
Cystic and solid on gross exam;
may be supratentorial;
Rosenthal fibers-eosinophilic, corkscrew fibers;
GFAP +;
benign, good prognosis
Medulloblastoma
highly malignant childhood cerbellar tumor;
a form of primitive neuroectodermal tumor;
can compress 4th ventricle, causing hydrocephalus;
can send “drop metastases” to spinal cord;
Homer-Wright rosettes;
solid on gross exam;
small blue cells on histology
Ependymoma
Childhood Ependymal cell tumors most commonly found in 4th ventricle;
can cause hydrocephalus;
poor prognosis;
characteristic perivascular rosettes;
rod-shaped blepharoplasts (basal ciliary bodies) found near nucleus
Craniopharyngioma
Benign childhood tumor, may be confused with pituitary adenoma (both can cause bitemporal hemianopia);
most common childhood supratentorial tumor;
derived from remnants of Rathke pouch;
Calcification is common (tooth enamel like)
Effect on glaucoma: epinephrine
alpha agonist;
decrease aqueous humor synthesis via vasoconstriction;
Side effects are mydriasis, do not use in closed angle glaucoma
Effect on glaucoma: Brimonidine
Alpha 2 agonist;
decrease aqueous humor synthesis;
side effects are blurry vision, ocular hyperemia, foreign body sensation, ocular allergic reactions, ocular pruritus
Effect on glaucoma: timolog, betaxolol, carteolol
beta blockers;
decrease aqueous humor synthesis;
side effects are no pupillary or vision changes
Effect on glaucoma: acetazolamide
Decrease aqueous humor synthesis via inhibition of carbonic anhydrase;
Side effects are no pupillary or vision changes
Effect on glaucoma: direct and indirect cholinomimetics
direct-pilocarpine, carbachol;
indirect-physostigmine and echothiophate;
increase outflow of aqueous humor via contraction of ciliary muscle and opening of trabecular meshwork;
Use pilocarpine in emergencies-very effective at opening meshwork into canal of Schlemm;
Side effects are miosis and cyclospasm (contraction of ciliary muscles)
Effect on glaucoma: Latanoprost (PGF2alpha)
Increased outflow of aqueous humor;
Side effect of darkening color of iris (browning)
Opioid analgesics: drug names
morphine, fentanyl, codeine, loperamide, methadone, meperidine, dextromethorphan, diphenoxylate;
Opioid analgesics: mechanism
act as agonists at opioid receptors (mu= morphine, delta= enkephalin, kappa= dynorphin) to modulate synaptic transmission- open K+ channels, close Ca2+ channels leading to decrease synaptic transmission;
Inhibit release of ACh, NE, 5-HT, glutamate, substance P
Opioid analgesics: Clinical use
Pain, cough suppression (dextromethorphan), diarrhea (loperamide and diphenoxylate), acute pulmonary edema, maintenance programs for heroin addicts (methadone)
Opioid analgesics: Toxicity
Addiction, respiratory depression, constipation, miosis (pinpoint pupils), additive CNS depression with other drugs;
Tolerance does not develop to miosis and constipation;
toxicity treated with naloxone or naltrexone (opioid receptor antagonist)
Butorphanol
Mechanism: Mu-opioid receptor partial agonist and kappa-opioid receptor agonist, produces analgesia;
Clinical use: severe pain (migraine, labor, etc.), causes less respiratory depression than full opioid agonists;
Toxicity: can cause opioid withdrawal symptoms if patient is also taking full opioid agonist (competition for opioid receptors), overdose not easily reversed with naloxone
Tramadol
Mechanism: very weak opioid agonist, also inhibits serotonin and NE reuptake (works on multiple neurotransmitters- “tram-it all” in with tramadol);
Used in chronic pain;
Toxicity: similar to opioids, decreases seizure threshold, serotonin syndrome
Ethosuxamide
Used for generalized absence seizures;
mechanism- blocks thalamic T type Ca2+ channels;
side effects of GI, fatigue, headache, urticaria, steven-johnson, EFGHIJ (ethosuximide causes Fatigue, Gi distress, Headache, Itching, and steven Johnson);
SUX to have Silent Seizures
Benzodiazepines
Names: diazepam, lorazepam;
used for status epilepticus;
mechanism: increased GABA-a action (increases frequency of Cl- channel opening);
Side effects: sedation, tolerance, dependence, respiratory depression;
also used for eclampsia seizure after MgSO4
Phenytoin
Used for simple, complex, tonic-clonic, status epilepticus;
increased Na+ channel inactivation;
zero-order kinetics;
Side effects of nystagmus, diplopia, ataxia, sedation, gingival hyperplasia, hirsutism, peripheral neuropathy, megaloblastic anemia, teratogenesis (fetal hydantoin syndrome) SLE-like syndrome, induction of cyp P-450, lymphadenopathy, Steven Johnson, osteopenia
Carbamazepine
Used for simple, complex, and tonic-clonic;
increased Na+ channel inactivation;
Side effects-Diplopia, ataxia, blood dyscrasias (agranulocytosis, aplastic anemia), liver toxicity, teratogenesis, induction of cyp P450, SIADH, steven johnson;
1st line for trigeminal neuralgia
Valproic acid
Used for simple, complex, tonic-clonic, and absence seizures;
Increased Na+ channel inactivation, increased GABA concentration by inhibiting GABA transaminase;
Side effects are GI, distress, rare but fatal, hepatotoxicity (measure LFTs), neural tube defects in fetus (spina bifida), tremor, weight gain, contraindicated in pregnancy;
Also used for myoclonic seizures, bipolar disorder
Gabapentin
Simple, Complex, tonic-clonic seizures;
Primarily inhibits high voltage-activated Ca2+ channels, designed as GABA analog;
side effects sedation and ataxia;
Also used for peripheral neuropathy, postherpetic neuralgia, migraine prophylaxis, bipolar disorder
Phenobarbital
used for simple, complex, tonic-clonic seizures;
increased GABAa action (increases the duration of opening Cl channel)
Topiramate
For simple, complex and tonic clonic;
blocks Na+ channels, increased Gaba action;
Side effects are Sedation, mental dulling, kidney stones, weight loss;
Also used for migraine prevention
Lamotrigine
For simple, complex, tonic-clonic, absence;
blocks voltage-gated Na channels;
Side effects are steven johnson (titrate slowly)
Levetiracetam
For simple, complex, and tonic clonic;
Mechanism is unknown, may modulate GABA and glutamate release
Tiagabine
for simple, complex seizures;
increases GABA by inhibiting re-uptake
Vigabatrin
Simple and complex seizures;
Increase GABA by irreversibly inhibiting GABA transaminase
barbiturates
Names: phenobarbital, pentobarbital, thiopental, secobarbital;
Mechanism: facilitate GABAa action by increasing duration of Cl- channel opening, thus decrease neuron firing;
Contraindicated in porphyria;
Used for: sedative for anxiety, seizures, insomnia, induction of anesthesia (thiopental);
Toxicity: respiratory and cardiovascular depression (Can be fatal); CNS depression (can be exacerbated by EtOH use), dependence, drug interactions (induces cyp P-450), overdose treatment is supportive (assist respiration and maintain BP)
Benzodiazepines: names
Diazepam, lorazepam, triazolam, temazepam, oxazepam, midazolam, chlordiazepoxide, alprazolam
Benzodiazepines: mechanism
Facilitate GABAa action by increased frequency of Cl- channel opening;
decrease REM sleep;
most have long half-lives and active metabolites (exceptions: triazolam, oxazepam, and midazolam are short acting leading to higher addictive potential)
Benzodiazepines: Uses
Anxiety, spasticity, status epilepticus (lorazepam and diazepam), detoxification (especially alcohol withdrawal-DTs), night terrors, sleepwalking, general anesthetic (amnesia, muscle relaxation), hypnotic (insomnia)
Benzodiazepines: toxicity
Dependence, additive CNS depression effects with alcohol;
less risk of respiratory depression and coma than with barbiturates;
treat overdose with flumazenil (competitive antagonist at GABA benzodiazepine receptor)
Benzo, barbs, and EtOH all bind what
bind the GABAa receptor, which is a ligand-gated Cl- channel
Nonbenzodiazepine hypnotics: names
Zolpidem (ambien), Zaleplon, esZopiclone (ZZZs put you to sleep);
Nonbenzodiazepine hypnotics: mechanism
act via the BZ1 subtype of the GABA receptor
Nonbenzodiazepine hypnotics: Clinical use
insomnia
Nonbenzodiazepine hypnotics: Toxicity
ataxia, headaches, confusion;
short duration because of rapid metabolism by liver enzymes;
unlike older sedative-hypnotics, cause only modest day after psychomotor depression and few amnestic effecs;
decreased dependence risk compared to benzodiazepines
Nonbenzodiazepine hypnotics: treat toxicity with
Effects reversed by flumazenil
Anesthetics-general principles
CNS drugs must be lipid soluble (cross BBB) or be actively transported;
Drugs with decreased solubility in blood=rapid induction and recovery times;
drugs with increase solubility= increased potency= 1/MAC;
what is the minimal alveolar concentration
(of inhaled anesthetic) required to prevent 50% of subjects from moving in response to noxious stimulus (e.g. skin incision)
inhaled anesthetics: names
halothane, enflurance, isoflurane, sevoflurane, methoxyflurane, nitrous oxide
inhaled anesthetics: effects
Myocardial depression, respiratory depression, nausea/emesis, increased cerebral blood flow (decrease cerebral metabolic demand)
inhaled anesthetics: toxicity
Hepatotoxicity (halothane), nephrotoxicity (methoxyflurane), proconvulsant (enflurane), expansion of trapped gas in a body cavity (nitrous oxide);
can cause malignant hyperthermia
Malignant hyperthermia
rare, life-threatening hereditary condition in which inhaled anesthetics (except nitrous oxide) and succinylcholine induce fever and severe muscle contractions;
treat with dantrolene
Barbiturates: intravenous anesthetics
Thiopental-high potency, high lipid solubility, rapid entry into brain;
used for induction of anesthesia and short surgical procedures;
effect terminated by rapid redistribution into tissue (i.e. skeletal muscle) and fat;
decreased cerebral blood flow
Benzodiazepines: intravenous anesthetics
Midazolam most common drug used for endoscopy;
used adjunctively with gaseous anesthetics and narcotics;
may cause severe postoperative respiratory depression, decreased BP, and anterograde amnesia;
treat overdose with flumazenil
Arylcyclohexylamines (ketamine)
PCP analogs that act as dissociative anesthetics;
block NMDA receptors;
cardiovascular stimulants;
cause disorietnation, hallucinations, and bad dreams;
increase cerebral blood flow;
Opioids: intravenous anesthetics
Morphine, fentanyl used with other CNS depressants during general anesthesia
Propofol: intravenous anesthetics
Used for sedation in ICU, rapid anesthesia induction, and short procedures;
less postoperative nausea than thiopental;
potentiates GABAa
Local anesthetics: names
Esters (procaine, cocaine, tetracaine);
Amides (Lidocaine, mepivacaine, bupivacaine, (amides have 2 I’s))
Local anesthetics: mechanism
Block Na channels by binding to specific receptors on inner portion of channel;
preferentially bind to activated Na channels, so most effective in rapidly firing neuorns;
Tertiary amine local anesthetics penetrate membrane in uncharged form, then bind to ion channels as charged form
Local anesthetics: order of nerves they block
small diameter blocked before big;
myelinated fibers blocked before unmyelinated fibers;
overall, size matters more than myelination;
Lose 1)pain then 2) temperature then 3) touch 4) pressure
Local anesthetics: Toxicity
CNS excitation, severe cardiovascular toxicity (bupivacaine), HTN, hypotension, and arrhythmias (cocaine)
Neuromuscular blocking drugs: depolarizing
Succinylcholine- strong ACh receptor agonist;
produces sustained depolarization and prevents muscle contraction;
reversal of blockade: Phase 1- (prolonged depolarization)-no antidote. Block potentiated by cholinesterase inhibitors;
Phase 2- (repolarized but blocked, ACh receptors are available, but desensitized)-antidote consists of cholinesterase inhibitors;
Complication include hypercalcemia, hyperkalemia, and malignant hyperthermia
Neuromuscular blocking drugs: Nondepolarizing
Tubocurarine, atracurium, mivacurium, pancuronium, vecuronium, rocuronium- competitive antagonists-compete with ACh for receptors;
Reversal of blockade-neostigmine (must be given with atropine to prevent muscarinic effects such as bradycardia), edrophonium, and other cholinesterase inhibitors
Dantrolene
Prevents the release of Calcium from the sarcoplasmic reticulum of skeletal muscle;
Uses: used to treat malignant hyperthermia and neuroleptic malignant syndrome (a toxicity of antipsychotic drugs)
Parkinson disease drugs: dopamine agonists
Bromocriptine (ergot), pramipexole, ropinirole (non-ergot);
non-ergots are preferred;
Parkinson disease drugs: increased dopamine
Amantadine (may increase dopamine release);
also used as an antiviral against influenza A and rubella;
toxicity=ataxia;
L-dopa/Carbidopa (converted to dopamine in CNS)
Parkinson disease drugs: Prevent dopamine breakdown
Selegiline (selective MAO type B inhibitor);
entacapone, tolcapone (COMT inhibitors- prevent L-dopa degradation leading to increased dopamine availability)
Parkinson disease drugs: curb excess cholinergic activity
Benztropine (antimuscarinic; improves tremor and rigidity but has little effect on bradykinesia);
Park your Benz
L-dopa(levodopa)/carbidopa: Mechanism
increased level of dopamine in brain;
unlike dopamine, L-dopa can cross BBB and is converted by dope decarboxylase in the CNS to dopamine;
carbidopa, an peripheral decarboxylase inhibitor, is given with L-dopa to increased the bioavailability of L-dopa in the brain and to limit peripheral side effects;
L-dopa(levodopa)/carbidopa: Clinical use
Parkinson disease
L-dopa(levodopa)/carbidopa: toxicity
Arrhythmias form increased peripheral formation of catecholamines;
long-term use can lead to dyskinesia following administration (“on/off” phenomenon), akinesia between doses
Selegiline
Mechanism: selectively inhibits MAO-B, which preferentially metabolized dopamine over NE and 5-HT, thereby increased the availability of dopamine;
Clinic use: adjunctive agent to L-Dopa in treatment of Parkinson disease;
Toxicity: may enhance adverse effects of L-dopa
Memantine
Alzheimer drug;
Mechanism: NMDA receptor antagonists, helps prevents excitotoxicity (mediated by Ca2+);
Toxicity: dizziness, confusion, hallucinations
Donepexil, galantamine, rivastigmine
Alzheimer drugs;
Mechanism: AChE inhibitors;
Toxicity: nausea, dizziness, insomnia
Neurotransmitter changes in Huntington disease
decreased GABA, Decreased ACh, increased dopamine
Medications for Huntington disease
Tetrabenazine and reserpine- inhibit vesicular monoamine transporter (VMAT), limit dopamine vesicle packaging and release;
Haloperidol- dopamine receptor antagonist
Sumatriptan
Mechanism: 5-HT(1B/1D) agonist;
inhibits trigeminal nerve activation, prevents vasoactive peptide release, induces vasoconstriction;
half life
