Neurology Flashcards
Neural development
The notochord induces overlying ectoderm to differentiate into neuroectoderm and form neural plate around day 18. Neural plate gives rise to neural tube and neural crest cells around day 21. Notochord becomes nucleus pulposus of intervertebral disc in adults. The alar plate is dorsal in responsible for sensory. Basal plate is ventral and is responsible for motor.
The three primary vesicles of the developing brain
Prosencephalon (forebrain), mesencephalon (midbrain), rhombencephalon (hindbrain).
Prosencephalon
The forebrain. It differentiates into telencephalon and diencephalon.
Mesencephalon
The midbrain. It differentiates into the secondary mesencephalon.
Rhombencephalon
The hindbrain. It differentiates into the metencephalon and the myelencephalon.
Telencephalon
Derived from the prosencephalon. It differentiates into the cerebral hemispheres and the lateral ventricles.
Diencephalon
It is derived from the prosencephalon. It differentiates into the thalamus and the third ventricle.
Mesencephalon
It differentiates into the midbrain and the aqueduct.
Metencephalon
It is derived from the rhombencephalon. It differentiates into the pons and cerebellum and the upper part of fourth ventricle.
Myelencephalon
It is derived from the rhombencephalon. It differentiates into the medulla and the lower part of the fourth ventricle.
Derivatives of neuroectoderm
It differentiates into CNS neurons, ependymal cells (inner lining of ventricles, make CSF), oligodendroglia, astrocytes.
Derivatives of neural crest
PNS neurons, Schwann cells
Mesoderm
Microglia (like Macrophages, originate from Mesoderm).
Neural tube defects
If neuropores fail to fuse (during the fourth week), than there is a persistent connection between amniotic cavity and the spinal canal. It is associated with low folic acid intake before conception and during pregnancy. There will be an increase in alpha fetoprotein (AFP) in amniotic fluid and maternal serum. Acetylcholinesterase increases in amniotic fluid (fetal AChE in CSF transudates across defect into amniotic fluid). Defects include spina bifida occulta, meningocele, meningomyelocele, and anencephaly.
Spina bifida occulta
There is failure of bony spinal canal to close, but no structural herniation. It is usually seen at lower vertebral levels. The dura is still intact. It is associated with a tuft of hair or dimple at the level of the bony defect. There will be normal AFP. It is the most common neural tube defect.
Meningocele
Meninges (but no neural tissue) herniate through bony defect
Meningomyelocele
Meninges and neural tissue herniate through bony defect.
Anencephaly
A malformation of the anterior resulting in no forebrain and an open calvarium. Clinical findings include an increase in AFP, polyhydramnios (due to no swallowing center in the brain). It is associated with maternal type 1 diabetes. Maternal folate supplementation decreases risk.
Holoprosencephaly
A failure of left and right hemispheres to separate. It usually occurs during weeks 5-6. It may be related to mutations in sonic hedgehog signaling pathway. A moderate form has a cleft lip/palate; the more severe form results in cyclopia. It is seen Patau syndrome and fetal alcohol syndrome.
Chiari I malformation
Cerebellar tonsillar ectopia greater than 3-5 mm. Results in syringomyelia. It is congenital, usually asymptomatic in childhood and manifests with headaches and cerebellar symptoms.
Chiari II malformation
A significant herniation of cerebellar tonsils and vermis through foramen magnum with aqueductal stenosis and hydrocephalus. It often presents with lumbosacral meningomyelocele and paralysis below the defect.
Dandy Walker malformation
Agenesis of the cerebellar vermis with cystic enlargement of the 4th ventricle, which fills the enlarged posterior fossa. It is associated with hydrocephalus and spina
Syringomyelia
A cystic cavity (syrinx) within the spinal cord. If it occurs within the central canal than it can lead to hydromyelia (abnormal widening of the central canal). The crossing anterior spinal commussural fibers are usually damaged first, which results in a cape like, bilateral loss of pain and temperature sensation in the upper extremities (fine touch sensation is preserved). It is associated with Chiari malformations, trauma, and tumors. Syrinx= tube, as in a syringe. It is most common at C8-T1. MRI will show low lying cerebellar tonsils (Chiari I) and fluid filled cavity in spinal cord (syrinx).
Tongue development
The 1st and 2nd brachial arches form the anterior 2/3 (thus sensation via CN V3 and taste via CN VII). the 3rd and 4th branchial arches form the posterior 1/3 (thus sensation and tasted mainly via CN IX, extreme posterior via CN X).
CN responsible for taste
Anterior 2/3 of tongue is CN VII, posterior 1/3 of tongue is CN IX, extreme posterior is CN X.
CN responsible for pain in the tongue
Anterior 2/3 of tongue is CN V3, posterior 1/3 of tongue is CN IX, extreme posterior is CN X.
CN responsible for motor in the tongue
Motor innervation is via CN XII to hyoglossus (retracts and depresses tongue), genioglossus (protrudes tongue), and styloglossus (draws sides of tongue upwards to create a trough for swallowing). Motor innervation is via CN X to palatoglosus (elevates tongue during swallowing).
Nissle stain
Stains cell bodies and dendrites of neurons by staining RER. RER is not present in axons.
Wallerian degeneration
Occurs due to injury of an axon. There is degeneration distal to the injury and axonal retraction proximally. There can be regeneration of axon if it is in the PNS.
Astrocytes
Responsible for physical support, repair, K metabolism, removal of excess neurotransmitter, component of blood-brain barrier, glycogen fuel reserve buffer. Undergoes reactive gliosis (reactive change of glial cells in response to damage). Astrocyte marker in GFAP. It is derived from neuroectoderm.
Microglia
Phagocytic scavenger cells of CNS (mesodermal, mononuclear origin). It is activated in response to tissue damage. It is not readily discernible by a Nissl stain. HIV-infected microglia fuse to form multinucleated giant cells in the CNS.
Myelin
It increases conduction velocity of signals transmitted down axons causing saltatory conduction action potential at the nodes of Ranvier, where there are high concentrations of Ca channels. In CNS, oligodendrocytes myelinate. In PNS, Schwanna cells myelinate. They wrap and insulate axons, increase space constant and increasing conduction velocity.
Schwann cells
Each cell myelinates only 1 PNS axon. Also promote axonal regeneration. Derived from neural crest cells. It increases conduction at nodes of Ranvier, where there is a high concentration of Na channels. They may be injured in Guillain Barre syndrome.
Acoustic neuroma
Occurs in a type of schwannoma. It typically is located in the internal acoustic meatus (CN VII). If bilateral, it is strongly associated with neurofibromatosis type 2.
Oligodendroglia
Myelinates axons of neurons in CNS. Each one can myelinate many axons (around 30). It is the predominant type of glial cell in white matter. It is derived from neuroectroderm. It has a fried egg appearance on histology. It is injured in multiple sclerosis, progressive multifocal leukoencephalopathy (PML), and leukodystrophies.
C nerve fibers
Unmyelinated fibers, slow. In skin, epidermis, and some viscera. It senses pain and temperature.
A-gamma nerve fibers
Myelinated fibers, fast. In skin, epidermis, and some viscera. It senses pain and temperature.
Meissner corpuscles
Large, myelinated fibers; adapt quickly. They are present in glabrous (hairless) skin. It senses dynamic, fine/light touch, position sense.
Pacinian corpuscles
They are large, myelinated, and adapt quickly. They are located in the deep skin layers, ligaments, and joints. It senses vibration and pressure.
Merkel discs
Large, myelinated, adapt slowly. It is located in finger tips and superficial skin. It senses pressure, deep static touch (eg shapes, edges), position sense.
Ruffini corpuscles
Dendritic endings with capsule, adapt slowly. It is located in finger tips and joints. They sense pressure, slippage of objects along surface of skin, and joint angle change.
Endoneurium
invests single nerve fiber layers (inflammatory infiltrate in Guillain- Barre syndrome)
Perineurium
Permible barrier. Surrounds a fascicle of nerve fibers. Must be rejoined in microsurgery for limb reattachment.
Epineurium
Dense connective tissue that surrounds entire nerve (fascicles and blood vessels).
norepinephrine
It increases with anxiety and decreases in depression. It is synthesized in the locus ceruleus (responsible for stress and panic) in the pons.
Dopamine
It increases in Huntington disease and decreases in Parkinson disease and depression. It is synthesized in the ventral tegmentum and substantia nigra pars compacta (midbrain)
5-HT
It decreases in anxiety and depression. It is synthesized in the raphe nuclei in the pons, medulla, and midbrain.
ACh
It increases in Parkinson disease and decreases in Alzheimer and Huntington disease. It is synthesized in the basal nucleus of Meynert.
GABA
It decreases in anxiety and Huntington disease. It is synthesized in the nucleus accumbens (the nucleus accumbens and septal nucleus is the reward center, pleasure, addiction, and fear).
Blood brain barrier
Prevents circulating blood substances (eg bacteria or drugs) from reaching the CSF/CNS. Formed by three structures including tight junctions between non-fenestrated capillary endothelial cells, basement membrane, and astrocyte foot processes. Glucose and amino acids crass slowly by carrier mediated transport mechanisms. Nonpolar/lipid-soluble substances cross rapidly via diffusion. A few specialized regions with fenestrated capillaries and no blood brain barrier allows molecules in the blood to affect brain function (eg area protrema-vomitting after chemo; organum vasculosum of the lamina terminalis (OVLT)- osmotic sensing) or neurosecretory products to enter circulation (eg neurohypophysis-ADH release). Infarction and/or neoplasm destroy endothelial cell tight junctions leads to vasogenic edema. Other notable barriers are the blood testis barrier and maternal fetal blood barrier of placenta.
hypothalamus
The hypothalamus wears TAN HATS: Thirst and water balance, Adenohypophysis control (regulates anterior pituitary), Neurohypophysis releases hormones produced in the hypothalamus, Hunger, Autonomic regulation, Temperature regulation, Sexual urges. Inputs (areas not protected by the blood brain barrier) includes OVLT (organum vasculosum of the lamina terminalis-senses changes in osmolarity), area postrema (responds to emetics). Paraventricular nucleus primarily makes oxytocin. ADH and oxytocin is made by the hypothalamus but is stored and released in the posterior pituitary.
Supraoptic nucleus
Apart of the hypothalamus. Supraoptic nucleus primarily makes ADH.
Paraventricular nucleus
Apart of the hypothalamus. Paraventricular nucleus primarily makes oxytocin.
organum vasculosum of the lamina terminalis
Apart of the hypothalamus, senses changes in osmolarity
area postrema
Apart of the hypothalamus, responds to emetics
Lateral area of the hypothalamus
Controls hunger. Destruction causes anorexia, failure to thrive in infants. It is inhibited by leptin. If you zap the lateral nucleus, you shrink laterally.
Vertomedial area of the hypothalamus
Control satiety. Destruction (eg craniopharyngioma) leads to hyperphagia. It is stimulated by leptin. If you zap your ventromedial nucleus, you grow ventrally and medially.
Anterior hypothalamus
Controls cooling, under parasympathetic control. Anterior nucleus= cool off (cooling, pArasympathetic). A/C=anterior cooling.
Posterior hypothalamus
Controls heating, under sympathetic control. Posterior nucleus= get fired up (heating, sympathetic). If you zap your posterior hypothalamus, you become a Poikilotherm (cold blooded, like a snake).
Suprachiasmatic nucleus
Controls circadian rhythm. You need to sleep to be charismatic (chiasmatic).
Sleep physiology
Sleep cycles are regulated by the circadian rhythm, which is driven by suprachiasmatic nucleus (SCN) of the sypothalamus. Circadian rhythm controls nocternal release of ACTH, prolactin, melatonin, norepinephrine. The activated SCN releases norepinephrine, which acts on the pineal gland to secrete melatonin. SCN is regulated by the environment (eg light). There are two stages: rapid eye movement (REM) and non-REM. Extreaocular movements during REM sleep due to activity of PPRF (paramedian pontine reticular formation/conjugate gaze center). REM sleep occurs every 90 minutes, and duration increases through the night. Alcohol, benzodiazepines, and barbiturates are associated with a decrease in REM sleep and delta wave sleep; norepinephrine also decreases REM sleep.
Treating bedwetting
Treat bedwetting (sleep enuresis) with oral desmopressin (ADH analog). It is prefered over imipramine because of adverse side effects.
Treating night terrors and sleepwalking
Benzodiazepines.
Beta EEG waves
Highest frequency, lowest amplitude. It is active during being awake with eyes open and alert with active mental concentration.
Alpha EEG waves
Active with being awake and eyes closed
Theta EEG waves
Active during stage N1 (5%), which is light sleep.
Sleep spindles and K complexes
Active during stage N2 (45%), which is deeper sleep when bruxism (nocturnal tooth grinding) occurs.
Delta EEG waves
The lowest frequency and highest amplitude. Active during stage N3 (25%). It is the deepest non-REM sleep (slow-wave sleep). This is when sleepwalking, night terrors, and bedwetting occurs.
REM sleep
Occurs 25% of the time. There are beta waves. There is a loss of motor tone, increase brain O2 use, increases and variable pulse and blood pressure. This is when dreaming and penile/clitoral tumescence may occur. It may serve for memory processing function.
EEG wave form order (from wakefulness to REM)
Beta, Alpha, Theta, Sleep spindles and K complexes, Delta, and Beta. At nigh, BATS Drink Blood.
Thalamus
major relay for all ascending sensory information except for olfaction.
Ventral posterolateral nucleus (VPL)
Apart of the thalamus. Receives input from the spinothalamic (pain and temperature) and dorsal columns/medial lemniscus (touch, pressure, vibration and proprioception. It relays info to the primary somatosensory cortex.
Ventral posteromedial nucleus (VPM)
Apart of the thalamus. Receives input from the trigeminal (face sensation) and gustatory (taste) pathway. It relays info to the primary somatosensory cortex. Makeup goes on the face (vpM)
Lateral geniculate nucleus (LGN)
Apart of the thalamus. Receives input from CN II (vision) and relays info to the calcarine sulcus (the primary visual cortex in the frontal cortex). (Lateral=Light).
Medial geniculate nucleus (MGN)
Apart of the thalamus. Receives input from the superior olive and inferior colliculus of tectum (hearing) and relays info to the auditory cortex of the temporal lobe. Medial=Music
Ventral lateral nucleus
Apart of the thalamus. Receives input from the basal ganglia and cerebellum (motor) and relays info to the motor cortex.
Limbic system
A collection of neural structures involved in emotion, long-term memory, olfaction, behavior modulation, ANS function. Structures include hippocampus, amygdala, fornix, mammillary bodies, cingulate gyrus. It is responsible for Feeding, Fleeing, Fighting, Feeling, and Sex. The famous 5 F’S.
Osmotic demyelination syndrome (central pontine myelinolysis)
Acute paralysis, dysarthria, dysphagia, diplopia, loss of consciousness. It can cause locked in syndrome. A massive demyelination in pontine white matter secondary to osmotic changes. It is commonly iatrogenic, caused by overly rapid correction of hyponatremia. In contrast, correcting hypernatremia too quickly results in cerebral edema/ herniation. Correcting serum too fast from low to high, your pons will die; from high to low, your brain will blow.
Cerebellum
It modulates movement; aids in coordination and balance.
Inputs into cerebellum
Inputs include contralateral cortex via middle cerebellar peduncle. Ipsilateral proprioceptive information via inferior cerebellar peduncle from spinal cord.
Outputs from cerebellum
Sends information to contralateral cortex to modulate movement. Output nerves are Perkinje cells, which synapse on the deep nuclei of the cerebellum, which synapses on the contralateral cortex via the superior cerebellar peduncle. The deep nuclei, from lateral to medial, the four deep cerebellar nuclei are the dentate, emboliform, globose, and fastigii. Don’t Eat Greasy Foods.
Lateral lesions of the cerebellum
This part is responsible for voluntary movement of extremities. When injured, propensity to fall toward injured (ipsilateral) side.
Medial lesions of the cerebellum
Lesions involving the midline structures (vermal cortex, fastigial nuclei) and/or flocculonodular lobe causes truncal ataxia (wide-based cerebellar gait), nystagmus, head tilting. Generally, midline lesions result in bilateral motor deficits affecting axial and proximal limb musculature.
Basal ganglia
Important in voluntary movements and making postural adjustments. It receives cortical input and provides negative feedback to cortex to modulate movement.
Striatum
Putamen (motor) and caudate (cognitive)
Lentiform
Putamen and globus pallidus.
D1-Receptor
Dopamine binds to D1, stimulating the excitatory pathway, which facilitates movement.
D2-Receptor
Dopamine binds to D2, inhibiting the inhibitory pathway, which inhibits movement.
Excitatory pathway of the basal ganglia
The cortical inputs stimulate the striatum (putamen), stimulating the release of GABA, which disinhibits the thalamus via the globus pallidus internus/substantia nigra pars reticulata, increasing motion.
Inhibitory pathway of the basal ganglia
The cortical inputs stimulate the striatum (putamen), which disinhibits the subthalamic nucleus via the globus pallidus externus. The subthalamic nucleus stimulates the globus pallidus internus/substantia nigra pars reticulata to inhibit the thalamus, decreasing the motion.
Athetosis
Slow, writhing movements; especially seen in fingers. It is writhing, snake-like movement. The lesion is located in the basal ganglia (eg Huntington).
Chorea
Sudden jerky, purposeless movement. Chorea=dancing. The lesion is located in the basal ganglia (eg Huntington).
Dystonia
Sustained, involuntary muscle contraction. Examples include writer’s cramp; blepharospasm (sustained eye twitch).
Essential tremor
High-frequency tremor with sustained posture (eg outstretched arms), worsened with movement or when anxious. It is often familial. Patients often self-medicate with EtOH, which decreases the tremor’s amplitude. Treatment includes beta-blockers and primidone (a barbiturate).
Hemiballismus
Sudden, wild flailing of 1 arm, with or without the ipsilateral leg. It occurs due to a contralateral lesion in the subthalamic nucleus (eg lacunar stroke). “Half-of-body ballistic.”
Intention tremor
Slow, zigzag motion when pointing/extending toward a target. It is characteristic of cerebellar dysfunction.
Myoclonus
Sudden, brief, uncontrolled muscle contraction. It can present as jerks or hiccups (common in metabolic abnormalities such as renal and liver failure).
Resting tremor
Uncontrolled movement of distal appendages (most noticeable in hands). The tremor is alleviated by intentional movement. For example, pill-rolling tremor of Parkinson disease.
Parkinson disease
Degenerative disorder of CNS associated with Lewy bodies (composed of alpha-synuclein intracellular eosinophilic inclusions) and loss of dopaminergic neurons (ie depigmentation) of substantia nigra pars compacta. Parkinson TRAPS your body: Tremor (pill-rolling tremor at rest), Rigidity (cogwheel), Akinesia (or bradykinesia), Postural instability, Shuffling gait.
Huntington disease
Autosomal dominant trinucleotide repeat disorder on chromosome 4. Symptoms manifest between ages 20 and 50. It is characterized by choreiform movements, aggression, depression, and dementia (sometimes initially mistaken for substance abuse). There is an increase in dopamine and a decrease in GABA and ACh in the brain. Neuronal death occurs via NMDA-R binding and glutamate toxicity. Atrophy of the caudate nucleus with ex vaco dilation of frontal horns on MRI. There is expansion of CAG repeats (anticipation). CAG: Caudate loses ACh and GABA
Broca aphasia
The posterior part of the inferior frontal gyrus of the frontal lobe on the dominant side. Responsible for motor speech. Damage here causes nonfluent aphasia with intact comprehension and impaired repetition. Broca= broken boca. Damage often extends into the primary motor cortex and can be associated with contralateral facial or arm weakness. Patients are aware of deficit and are inevitably frustrated because of lack of ability to express themselves.
Dysarthria vs aphasia
motor inability to speak, a movement deficit. Meanwhile, aphasia is a higher order inability to speak, a language deficit.
Wernicke aphasia
Wernicke (sensory) aphasia occurs from damage to posterior part of the superior temporal gyrus on the dominant side leading to receptive, fluent aphasia (meaning the patient cannot understand any form of language but is able to verbalize fluently, except the speech lacks any meaning). Wernicke is Wordy but makes no sense (what?). In contrast to Broca aphasia, Wernicke aphasia patients are unaware of deficit and show no distress.
Conduction aphasia
Conduction aphasia results from damage to the arcuate fasciculus (connection between Wernicke’s and Broca’s areas). This results in the patient’s inability to repeat words back to someone but an intact ability to comprehend with fluent speech. For example, can’t repeat “no ifs, ands, or buts.”
Global aphasia
Global aphasia results from damage to Broca’s area, Wernicke’s area, and the arcuate fasciculus. This results in a patient with poor comprehension, nonfluent speech, and poor repetition.
Transcortical motor aphasia
Transcortical motor aphasia occurs from damage near Broca’s area producing a nonfluent aphasia where patients are able to comprehend and repeat words after the examiner.
Transcortical sensory aphasia
Transcortical sensory aphasia occurs from damage near Wernicke’s area producing an aphasia where patient are able to speak fluently and repeat words after the examiner, but with poor comprehension.
Mixed transcortical aphasia
Mixed transcortical aphasia is caused by damage to both Wernicke’s area and Broca’s area, but without damage to the arcuate fasciculus. The patient will have nonfluent speech and poor comprehension, but intact repetition.
Kluver-Bucy syndrome
It is characterized by disinhibited behavior (eg hyperphagia, hypersexuality, hyperorality). It occurs due to bilateral lesion of the amygdala. It is associated with HSV-1.
Frontal lobe lesion
Causes disinhibition and deficits in concentration, orientation, judgment. There may be reemergence of primitive reflexes.
Nondominant parietal-temporal cortex lesion
Causes hemispatial neglect syndrome (agnosia [inability to interpret sensations and hence to recognize things] of contralateral side of the world).
Dominant parietal-temporal cortex lesion
Causes Gerstmenn syndrome, which is marked by agraphia (loss in the ability to communicate through writing), acalculia (the inability to do simple mathematics problems), finger agnosia, left-right disorientation.
Reticular activating system lesion
Located in the midbrain. Causes reduced levels of arousal and wakefulness (eg coma).
Wernicke-Korsakoff syndrome
Bilateral lesion of mammillary bodies. Causes confusion, ophthalmoplegia, ataxia; memory loss (anterograde and retrograde amnesia), confabulation, personality changes. It is associated with thiamine (B1) deficiency and excessive EtOH use. It can be precipitated by giving glucose without B1 to a B1-deficient patient.
Basal ganglia lesion
May result in tremor at rest, chorea, and athetosis. Examples include Parkinson and Huntington disease.
Cerebellar hemisphere lesion
Causes intention tremor, limb ataxia, loss of balance. Damage to cerebellum causes ipsilateral deficits, falling toward side of lesion. Cerebellar hemispheres that are laterally located affect lateral limbs.
Cerebellar vermis lesion
Causes truncal ataxia and dysarthria. The vermis is centrally located, affects the central body.
Subthalamic nucleus lesion
Causes contralateral hemiballismus.
Hippocampus (bilateral) lesion
Anterograde amnesia, inability to make new memories.
Paramedian pontine reticular formation lesion
It is located anterior and lateral to the medial longitudinal fasciculus. Causes eyes to look away from side of lesion.
Frontal eye fields lesion
It is located in the frontal cortex. Causes eyes to look towards the lesion.
Anterior cerebral artery distribution
Supplies the anteromedial surface
Middle cerebral artery distribution
Supplies the lateral surface
Posterior cerebral artery
Supplies the posterior and inferior surface.
Watershed zones of the brain
Located between the anterior cerebral and middle cerebral; posterior cerebral and middle cerebral arteries. Damage in severe hypotension, causing upper leg and upper arm weakness, defects in higher order visual processing.
Homunculus
Topographic representation of motor and sensory areas in the cerebral cortex. Feet medially and face laterally.
Regulation of cerebral perfusion
Brain perfusion relies on tight autoregulation. Cerebral perfusion is primarily driven by PCO2 (PCO2 also modulates perfusion in severe hypoxia). Therapeutic hyperventilation (decreases PCO2) helps decrease intracranial pressure (ICP) in cases of acute cerebral edema (stroke, trauma) via vasoconstriction. It is the cause of fainting in panic attacks, due to a decrease perfusion.
Cerebral perfusion and blood pressure
Cerebral perfusion relies on a pressure gradient between mean arterial pressure (MAP) and ICP. A decrease in blood pressure or an increase in ICP causes a decrease in cerebral perfusion pressure (CPP). CPP=MAP-ICP. If CPP=0, there is no cerebral perfusion, which causes brain death.
Middle cerebral artery
Supplies the motor cortex (upper limb and face), lesions here cause contralateral paralysis of the upper limb and face. Also supplies sensory cortex (upper limb and face), lesion causes contralateral loss of sensation of the upper limb and face. Also supplies temporal lobe (Wenicke area) and frontal lobe (Broca area). A lesion here can cause aphasia if in dominant (usually left) hemisphere. Hemineglect if lesion is on the non dominant side (usually right).
Anterior cerebral artery
Supplies the motor cortex (lower limbs). A lesion here would cause contralateral paralysis. It also supplies the sensory cortex (lower limb) and a lesion here would cause loss of sensation on the contralateral lower limb.
Lenticulostriate artery
Supplies the stratum and internal capsule. A lesion would cause contralateral hemiparesis and hemiplegia. This is a common location of lacunar infarcts, secondary to unmanged hypertension.
Anterior spinal artery
Supplies the lateral corticospinal tract (carries motor), a lesion here causes contralateral hemiparesis of both the upper and lower limbs. It also supplies the medial lemniscus (carries vibratory and touch-pressure sense); a lesion here causes a decrease in contralateral proprioception. Strokes here are commonly bilateral.
Medial medullary syndrome
Stroke in the paramedian branches of the anterior spinal artery or vertebral arteries can produce a medial medullary syndrome, which presents with: Contralateral hemiparesis of the upper and lower limbs (lesion of lateral corticospinal tract); Contralateral decreased proprioception, vibration sense, and discriminative touch (lesion of medial lemniscus); Ipsilateral hypoglossal dysfunction with the tongue deviating to the ipsilateral side (lesion of caudal medulla)
Posterior inferior cerebellar artery
Supplies the lateral medulla, including the vestibular nuclei (vomiting, vertigo, nystagmus), lateral spinothalamic tract, spinal trigeminal nucleus (a decrease in pain and temperature sensation from ipsilateral face and contralateral body), nucleus ambiguus (dysphagia, hoarseness, decrease gag reflex), sympathetic fivers (ipsilateral horner syndrome), and inferior cerebellar peduncle (ataxia and dysmetria). A lesion here results in lateral medullary (Wallenberg) syndrome. Nucleus ambiguus effects are specific to PICA lesions. Don’t pick a (PICA) horse (hoarseness) that can’t eat (dysphagia).
Anterior inferior cerebellar artery
Supplies the lateral pons, which contain the cranial nerve nuclei, vestibular nuclei (vomiting vertigo, nystagmus), facial nucleus (paralysis of face, decrease of lacrimation, salivation, decrease in taste from anterior 2/3 of tongue), spinal trigeminal nucleus (ipsilateral decrease in pain and temperature of the face, contralateral decrease in pain and temperature of the body), cochlear nuclei, and sympathetic fibers. It also supplies the middle and inferior cerebellar peduncles (ataxia and dysmetria). Causes lateral pontine syndrome. Facial nucleus effects are specific to AICA lesions. “Facial droop means AICA’s pooped.”
Posterior cerebral artery
Supplies occipital cortex and visual cortex. Lesion here causes contralateral hemianopia (blindness over half the field of vision) with macular sparing.
Basilar artery
Supplies the pons, medulla, lower midbrain, corticospinal and corticobulbar tracts, ocular cranial nerve nuclei, paramedian pontine reticular formation. A lesion here preserves consciousness and blinking, but causes quadriplegia, loss of voluntary facial, mouth, and tongue movements. This is called locked in syndrome.
Anterior communicating artery
The most common lesion here is aneurysm, which can lead to stroke. A saccular (berry) aneurysm can impinge cranial nerves. It usually manifests as visual field defects.
Posterior communicating artery
This is a common site of saccular aneurysm, not strokes. It can result in CN III palsy (eye is down and out with ptosis and mydriasis).
Saccular (berry) aneurysm
Occurs at bifurcations in the circle of Willis. Most common site is junction of anterior communicating artery and anterior cerebral artery. Rupture (the most common complication) causes subarachnoid hemorrhage (the worst headache of my life) or hemorrhagic stroke. It can also cause bitemporal heminopia via compression of the optic chiasm. It is associated with ADPKD, Ehlers-Danlos syndrome. Other risk factors include advanced age, hypertension, smoking, race (increase risk in blacks).
Charcot Bouchard microaneurysm
It is associated with chronic hypertension; affects small vessels (eg basal ganglia or thalamus).
Central post stroke pain syndrome
Neuropathic pain due to thalamic lesions. Initial paresthesias followed in weeks to months by allodynia (ordinarily painless stimuli cause pain) and dysesthesia. It occurs in 10% of stroke patients.
Epidural hematoma
Due to rupture of middle meningeal artery (branch of maxillary artery), often secondary to fracture of temporal bone. There is a lucid interval than rapid expansion under systemic arterial pressure causes transtentorial herniation, CN III palsy. CT shows biconvex (lentiform), hyperdense blood collection that does not cross suture lines. It can cross falx, tentorium.
Subdural hematoma
Rupture of bridging veins causing a slow venous bleeding (less pressure=hematoma develops over time). Seen in elderly individuals, alcoholics, blunt trauma, shaken baby (predisposing factors include brain atrophy, shaking, and whiplash). Crescent shaped hemorrhage that crosses suture lines. Mid line shift. Cannot cross falx, tentorium.
Subarachnoid hemorrhage
Rupture of an aneurysm (such as a berry aneurysm, as seen in Ehlers-Danlos syndrome, ADPKD) or arteriovenous malformation. There is a rapid time course. Patients complain of worst headache of my life. Bloody or yellow (xanthochromic) spinal tap. 2-3 days afterword, there is a risk of vasospasm due to blood breakdown (not visible on CT, treat with nimodipine) and rebleed (visible of CT).
Intraparenchymal hemorrhage
It is most commonly caused by systemic hypertension. It is also seen with amyloid angiopathy (recurrent lobar hemorrhagic stroke in elderly), vasculitis, neoplasm. Typically occurs in basal ganglia and internal capsule (Charcot Bouchard aneurysm of lenticulostriate vessels), but it can be lobar.
Ischemic brain disease, stroke
Irreversible damage begins after 5 minutes of hypoxia. The most vulnerable areas are the hippocampus, neocortix, cerebellum, watershed areas. It causes irreversible neuronal injury. Noncontrast CT to exclude hemorrhage (before tPA can be given). CT detects ischemic changes in 6-24 hours. Diffusion weighted MRI can detect ischemia within 3-30 min. With ischemic hypoxia, hippocampus is most vulnerable.
Histological features of stroke after 12-48 hours
Red neurons
Histological features of stroke after 24-72 hours
Necrosis plus neutrophils
Histological features of stroke after 3-5 days
Macrophages (microglia
Histological features of stroke after 1-2 weeks
Reactive gliosis plus vascular proliferation
Histological features of stroke after over 2 weeks
Glial scar
Hemorrhagic stroke
Intracerebral bleeding often due to hypertension, anticoagulation, cancer (abnormal vessels can bleed). It may be secondary to ischemic stroke followed by reperfusion (increases vessel fragility). Basal ganglia are most common site of intracerebral hemorrhage.
Ischemic stroke
Acute blockage of vessels cause a disruption of blood flow and subsequent ischemia, leads to liquefactive necrosis. There are three types: Thrombotic, embolic and hypoxic.
Thrombotic ischemic stroke
It occurs due to a clot forming directly at the site of infarction (commonly the MCA), usually over an atherosclerotic plaque.
Embolic ischemic stroke
An embolus from another part of the body obstructs vessel. It can affect multiple vascular territories. Examples include atrial fibrillation, DVT with patent foramen ovale.
Hypoxic ischemic stroke
It occurs due to hypoperfusion or hypoxemia. It is common during cardiovascular surgeries. It tends to affect watershed areas.
Treatment of ischemic stroke
tPA if within 3-4.5 hours of onset and no hemorrhage/ risk of hemorrhage. Reduce risk with medical therapy (eg aspirin, clopidogral). Optimum control of blood pressure, blood sugars, lipids. Treat conditions that could increase risk (eg A fib).
Transient ischemic attack
Brief, reversible episode of focal neurologic dysfunction without acute infarction (without MRI), with the majority resolving in under 15 minutes. Deficiets are due to focal ischemia.
Dural venous sinuses
Large venous channels that run through the dura. They drain the blood from cerebral veins and receive CSF from arachnoid granulations. They empty into the internal jugular vain.
Superior sagittal sinus (SSS)
The SSS is a large sinus between the two hemispheres. It is embedded within the falx cerebri and drains to the confluence of sinuses (which also receives blood from the straight sinus). In turn, the confluence empties laterally into the 2 transverse sinuses. A subdural hematoma forms when the cerebral veins draining to the SSS are ruptured during head trauma and appears as “crescent” shaped on imaging.
Transverse sinus
The transverse sinus is the lateral continuation of the confluence of sinuses. It curves inferiorly to become the sigmoid sinus.
Sigmoid sinus
The sigmoid sinus drains to the internal jugular vein.
Cavernous sinus
The cavernous sinus is located just lateral to the body of the sphenoid. Cranial nerves III, IV, V1, V2, VI, as well as the internal carotid artery, must pass through the cavernous sinus en route to their destinations.
Ventricular system
The lateral ventricle drains into the third ventricle via the right and left interventricular foramina of Monro. The third ventricle drains into the fourth ventricle via the cerebral aqueduct of Syvius. The fourth ventricle drains into the subarachnoid space via the foramina of Luscka (lateral) and the foramen of magendie (medial). CSF is made by the ependymal cells of choroid plexus, it is reabsorbed by the arachnoid granulations and then drains into the dural venous sinuses.
Idiopathic intracranial hypertension (pseudotumor cerebri)
An increase in ICP with no apparent cause on imaging (ie hydrocephalus, obstruction of CSF outflow). Patients present with headache, diplopia (usually from CN VI palsy), no mental status alterations. Papilledema seen on exam. risk factors include being a women of childbearing age, vitamin A excess, danazol. Lumbar puncture reveals increase of opening pressure and provides headache relief. Treatment include weight loss, acetazolamide, topiramate, invasive procedures for refractory cases (eg repeat lumbar puncture, CSF shunt placement, optic nerve fenestration surgery).
Communicating hydrocephalus
A decease in CSF absorption by arachnoid granulations cases an increase in ICP, papilledema, herniation (eg arachnoid scarring post-meningitis).
Normal pressure hydrocephalus
Affects the elderly. It is idiopathic. CSF pressure elevated only episodically. It does not result in increased subarachnoid space volume. Expansion of ventricles distorts the fibers of the corona radiata causing a triad of urinary incontinence, ataxia and cognitive dysfunction (sometimes reversible). “Wet, wobbly, and wacky”
Noncommunicating hydrocephalus
Caused by structural blockage of CSF circulation within ventricular system (eg stenosis of aqueduct of Sylvius; colloid cyst blocking foramen Monro).
Ex vacuo ventriculomegaly
Appearance of an increase CSF on imaging, is actually due to decreased brain tissue (neuronal atrophy) (eg Alzheimer disease, advanced HIV, Pick Disease). ICP is normal. Triad (Wet, wobbly, and wacky) is not seen.
Spinal nerves
There are 31 pairs of spinal nerve in total: 8 cervical, 12 thoracic, 5 lumbar, 5 sacral, 1 coccygeal. Nerves C1-C7 exit above the corresponding vertebra. C8 spinal nerves exits below C7 and above T1. All other nerves exit below (eg C3 exits above the 3rd cervical vertebra; L2 exits below the 2nd lumbar vertebra). There are 31, just like 31 flavors of Baskin-Robbins ice cream.
Vertebral disc herniation
The nucleus pulposus (soft central disc) herniates through annulus fibrosus (outer ring), usually occurs posterolaterally at L4-L5 or L5-S1.
Lower extent of spinal cord
In adults, spinal cord extends to lower border of L1-L2 vertebrae. Subarachnoid space (which contains the CSF) extends to lower border of S2 vertebra.
Lumbar puncture
Lumbar puncture is usually performed between L3-L4 or L4-L5 (level of cauda equina). Goal of lumbar puncture is to obtain sample of CSF without damaging spinal cord. To keep the cord alive, keep the spinal needle between L3 and L5.
Spinal cord and associated tracts
Legs (Lumbrosacral) are Lateral in Lateral corticospinal and spinothalamic tracts. Dorsal column is is organized as you are, with hands at sides. Arms outside legs inside.
Dorsal column
Ascending tract carrying info about pressure, vibration, fine touch, and proprioception. Fasciculus gracilis is medial and carries info from lower body and legs. The gasciculus cuneatus is lateral and carries info from upper body and arms. Sensory nerve endings carry info to cell body in dorsal root ganglion, which enters the spinal cord and ascends ipsilaterally in dorsal column. The first synapse is on the ipsilateral nucleus cuneatus or gracilis in the medulla. The second order neuron decussates in medulla and than ascends contralaterally in medial lemniscus. The second synapse occurs in the ventral posterolateral nucleus (VPL) in the thalamus. The 3rd order neuron travels to the sensory cortex.
Spinothalamic tract
Ascending tract. The lateral portion carries info about pain and temperature (the info from the sacral region travels laterally to the info from the cervical region). The anterior portion carries info about crude touch and pressure. Sensory nerve ending (Agamma and C fivers) (cell body in dorsal root ganglion) and enters the spinal cord. The first synapse occurs in the ipsilateral gray matter within the spinal cord. The second order neuron decussates at the anterior white commissure and ascends contralaterally. The second synapse occurs in the ventral posterolateral nucleus (VPL) in the thalamus. The 3rd order neuron travels to the sensory cortex.
Lateral corticospinal tract
A descending tract carrying info for voluntary movement of contralateral limbs. The cell body of the UMN located in the primary motor cortex and descends in ipsilaterally through the internal capsule. Most of the fibers decussate at caudal medulla in the pyramidal decussation and then descends contralaterally. The fibers that crossed (80%) travel in the lateral corticospinal tract with info traveling to sacral region most lateral and the info traveling to the cervical region being most medial. These fibers control movement in the limbs. The fibers that do not cross control the axial of the body and travel in the anterior corticospinal tract. The first synapse occurs on the cell bodies of the LMN in the anterior horn of the spinal cord. The LMN than leaves the spinal cord and synapses on the NMJ.
Signs of UMN lesion
weakness, hyperreflexia, increased tone, babinski sign (after the sole of the foot has been firmly stroked, the big toe then moves upward or toward the top surface of the foot), spastic paralysis, and clasp knife spasticity (a stretch reflex with a rapid decrease in resistance when attempting to flex a joint). Upper MN= everything UP (tone, DTRs, toes).
Signs of LMN lesion
Weakness, atrophy, fasciculations (muscle twitching), decrease reflexes, decrease tone, flaccid paralysis. Lower MN= everything lowered (less muscle mass, decrease muscle tone, decrease reflexes, down going toes).
Spinal lesion in Werdnig-Hoffmann disease
Poliomyelitis and spinal muscular atrophy. It is a LMN lesions due to destruction of the anterior horns and leads to flaccid paralysis.
Spinal lesion in Multiple sclerosis
Occurs due to demyelination. It most commonly effects the white matter of the cervical region. There are random and asymmetric lesions, due to demyelination. Produces scanning speech, intention tremor, and nystagmus.
Spinal lesion in Amyotrophic lateral sclerosis
There are combined UMN and LMN deficits with no sensory or oculomotor deficits. There are both UMN and LMN signs. It can be caused by a defect in superoxide dismutase 1. It commonly presents as fasciculations with eventual atrophy and weakness of hands. It is eventually fatal. Riluzole treatment modestly increases survival by decreasing presynaptic glutamate release. It is commonly known as Lou Gehrig disease. For LOU gehrig disease, give riLOUzole.
Spinal lesion in complete occlusion of the anterior spinal artery
It spares dorsal columns and Lissauer tract. The upper thoracic anterior spinal artery territory is watershed area, as artery of Adamkiewicz supplies ASA below T8.
Spinal lesion in Tabes dorsalis
It is caused tertiary syphilis. It results from degeneration (demyelination) of the dorsal columns and roots causes impaired sensation and proprioception, progressive sensory ataxia (inability to sense or feel the legs causing poor coordination). It is associated with Charcot joints, shooting pain, Argyll Robertson pupils. Exam will demonstrate absence of DTRs and positive Romberg sign (the standing patient is asked to close his or her eyes causing a loss of balance).
Spinal lesion in Syringomyelia
Syrinx expands an damages the anterior commissure of spinothalamic tract (2nd order neurons), which causes bilateral loss of pain and temperature sensation (usually C8-T1). It is seen with Chiari I malformation. It can expand and affect other tracts.
Spinal lesion in Vitamin B12 deficiency
Causes subacute combined degeneration due to demyelination of dorsal columns, lateral corticospinal tracts, and spinocerebellar tract, ataxie gait, paresthesia, impaired position and vibration sense.
Poliomyelitis
It is caused by poliovirus (fecal-oral transmission). It replicates in oropharynx and small intestine before spreading via the bloodstream to CNS. Infection causes destruction of cells in anterior horn of spinal cord leading to LMN death.
Symptoms of poliomyelitis
LMN lesion signs include weakness, hypotonia, flaccid paralysis, fasciculations, hyporeflexia, muscle atrophy. Signs of infection include malaise, headache, fever, nausea, etc.
Poliomyelitis findings
There wil be CSF with WBCs and slight increase of protein (with no change in CSF glucose).
Werdnig-Hoffmann disease
Spinal muscular atrophy. It is congenital degeneration of the anterior horns of spinal cord causing LMN lesion. It manifests as Flopping baby with marked hypotonia and tongue fasciculations. Infantile type has median age of death of 7 months. It is autosomal recessive inheritance.
Friedreich ataxia
It is an autosomal recessive trinucleotide repeat disorder (GAA) on chromosome 9 in gene that encodes frataxin (iron binding protein). It leads to impairment in mitochondria functioning. Degeneration of multiple spinal cord tracts causes muscle weakness and loss of DTRs, vibratory sense, proprioception. There is staggering gait, frequent falling nystagmus, dysarthria, pes cavus (high instep, high arch), hammer toes, diabetes mellitus, hypertrophic cardiomyopathy (cause of death). It presents in childhood with kyphoscoliosis. Friedreich is frastastic (frataxin): he;s your favorite Frat brother always Staggering and Falling but has a Sweet, Big Heart.
Brown Sequard syndrome
Hemisection of spinal cord. Findings include: ipsilateral UMN signs below level of lesion due to corticospinal tract damage; ipsilateral loss of tactile, vibration, proprioception sense below level of lesion (due to dorsal column damage); contralateral pain and temperature loss below level of lesion (due to spinothalamic tract damage); ipsilateral loss of all sensation at level of lesion; ipsilateral LMN signs (eg flaccid paralysis) at level of lesion. If lesio n occurs above T1, then patient may present with Horner syndrome due to damage of oculosympathetic athway.
C2 dermatome
posterior hald of skull “cap”
C3 dermatome
high turtleneck shirt.
C4 dermatome
low collar shirt
T4 dermatome
At the nipple. T4 at teat pore.
T7 dermatome
at the xiphoid process
T10 dermatome
at the umbilicus (important for early appendicitis pain referral). T10 at the belly button.
L1 dermatome
at inguinal ligament. L1 is IL (Inguinal Ligament).
L4 dermatome
includes the kneecap. Down on ALL 4’s (L4).
S2, S3, S4 dermatome
erection and sensation of penile and anal zones. S2, 3, 4 keep your penis off the floor.
Bicep reflex
C5 nerve root
Triceps reflex
C7 nerve root
Patella reflex
L4 nerve root
Achilles reflex
S1 nerve root
Reflexes in order
S1, 2 buckle my shoe (Achilles reflex); L3, 4 Kick the door (patellar reflex), C5, 6 pick up sticks (bicep reflex), C7, 8 lay them straight (triceps reflex). Additional reflexes include L1, L2 testicle move (cremaster reflex), S3, 4 winks galore (anal wink reflex).
Primitive reflexes
CNS reflexes that are present in a healthy infant, but are absent in a neurologically intact adult. normally disappear within first year of life. These primitive reflexes are inhibited by a mature/ developing frontal lobe. They amy reemerge in adults following frontal lobe lesion cause loss of inhibition of these reflexes.
Moro reflex
A primitive reflex. hang on for life reflex, abduct/ extended arms when startled, and then draw together.
Rooting reflex
A primitive reflex. Movement of head toward one side if cheek or mouth is stroked (nipple seeking).
Sucking reflex
A primitive reflex. Sucking response when roof of mouth is touched.
Palmar reflex
A primitive reflex. Curling of fingers is palm is stroked.
Plantar reflex
A primitive reflex. Dorsiflexion of large toe and fanning of other toes with plantar stimulation. Babinski sign is a presence of this reflex in an adult, which may signify an UMN lesion.
Galant reflex
A primitive reflex. Stroking along one side of the spine while newborn is in ventral suspension (face down) causes lateral flexion of lower body toward stimulated side.
CN nuclei that lie medially at brain stem
III, IV (arises dorsally and immediately decussates), VI, XII “Factors of 12, except 1 and 2”
Pineal gland
It is located near the center of the brain, between the two hemispheres, tucked in a groove where the two halves of the thalamus join. It is responsible for melatonin secretion, circadian rhythms.
Superior colliculi
The two superior colliculi sit below the thalamus and surround the pineal gland in the vertebrate midbrain. It is the conjugate vertical gaze center.
Inferior colliculi
The inferior colliculi of the midbrain are located just below the visual processing centers known as the superior colliculi. It is involved in auditory processing. Your eyes are above your ears, and the superior colliculus (visual) is above the inferior colliculus (auditory).
Parinaud syndrome
Paralysis of conjugate vertical gaze due to lesion in superior colliculi (eg stroke, hydrocephalus, pinealoma).
Location of cranial nerve nuclei
They are located in the tegmentum portion (a region of gray matter on either side of the cerebral aqueduct) of the brain stem (between the dorsal and ventral portions). The nuclei located in the midbrain include CN III and IV. The nuclei located in the pons include CN V, VI, VII, VIII. The nuclei located in the medulla include CN IX, X, XII. The nuclei located in the spinal cord include CN XI. Lateral nuclei are responsible for sensory (aLar plate). Medial nuclei are responsible for Motor (basal plate)
Structures passing through the cribiform plate
CN I
Structures passing through the middle cranial fossa (through the sphenoid bone)
CN II-VI
Structures passing through the optical canal
CN II, ophthalmic artery and central retinal vein
Structures passing through the superior orbital fissure
CN III, IV, V1, VI, ophthalmic vein and sympathetic fibers.
Structures passing through the foramen rotundum
CN V2
Structures passing through the foramen ovale
CN V3
Structures passing through the foramen spinosum
Middle meningeal artery
Structures passing through the posterior fossa (through the temporal or occipital bone)
CN VII-XII
Structures passing through the internal auditory meatus
CN VII, VIII
Structures passing through the jugular foramen
CN IX, X, XI, jugular vein
Structures passing through the hypoglossal canal
CN XII
Structures passing through the foramen magnum
spinal roots of CN XI, brain stem, vertebral arteries
Location of where CN V exit the cranium
V1 exits through the superior orbital fissure. V2 exits through the foramen rotundum. V3 exits through the formen ovale. Standing Room Only.
CN I
The olfactory nerve is a sensory nerve that is responsible for smell. It is the only CN without thalamic relay to cortex.
CN II
The optic nerve is a sensory nerve that is responsible for sight.
CN III
The oculomotor nerve is a motor nerve that is responsible for eye movement (SR, IR, MR, IO), pupillary constriction (sphincter pupillae from the Edinger-Westphal nucleus controlled muscarinic receptors), accommodation, eyelid opening (levator palpebrae)
CN IV
The trochlear nerve is a motor nerve that is responsible for eye movement (SO)
CN V
The trigeminal nerve is both a sensory and motor nerve that is responsible for mastication, facial sensation (ophthalmic, maxillary and mandibular divisions), somatosensation from anterior 2/3 of tongue.
CN VI
The abducens nerve is a motor nerve that is responsible for eye movement (LR)
CN VII
The facial nerve is both a motor and sensory nerve that is responsible for facial movement, taste from anterior 2/3 of tongue, lacrimation, salivation (submandibular and sublingual glands), eyelid closing (orbicularis oculi), stapedius muscle in ear (the nerve courses through the parotid gland, but does not innervate it).
CN VIII
The vestibulocochlear nerve is a sensory nerve that is responsible for hearing and balance.
CN IX
The glossopharyngeal nerve is both a sensory and motor nerve that is responsible for taste and somatosensation from posterior 1/3 of tongue, swallowing salivation (parotid gland), monitoring carotid body and sinus chemo and baroreceptors, and stylopharyngeus (elevates pharynx and larynx).
CN X
The vagus nerve is both a sensory and motor nerve that is responsible for taste from the epiglottic region, swallowing, soft palate elevation, midline uvula, talking, coughing, thoracoabdominal viscera, monitoring aortic arch chemo and baroreceptors.
CN XI
The accessory nerve is a motor nerve that is responsible for head turning, shoulder shrugging (sternocleidomastoid and trapezius).
CN XII
The hypoglossal nerve is a motor nerve that is responsible for tongue movement.
Vagal nuclei
Includes the nucleus solitarius, nucleus ambiguus, and dorsal motor nucleus.
Nucleus Solitarius
In the medulla. Responsible for visceral Sensory (Solitarius) information (eg taste, baroreceptors, gut distention). It receives input from CN VII, IX, and X.
Nucleus ambiguus
In the medulla. It is responsible for Motor (aMbiguus) innervation of the pharynx, larynx, upper esophagus (eg swallowing, palate elevation). It receives input from CN IX, X, and the cranial portion of XI.
Dorsal motor nucleus
In the medulla. It sends autonomic (parasympathetic) fibers to heart, lungs, and upper GI. It receives info from CN X.
Corneal reflex
Afferent control is CN V1 ophthalmic (nasociliary branch). Efferent control is CN VII (temporal branch and orbicularis oculi).
Lacrimation reflex
Afferent control is CN V1 (loss of reflex does not preclude emotional tears). Efferent control is CN VII.
Jaw jerk reflex
Afferent control is CN V3 (sensory muscle spindle from masseter). Efferent control is CN V3 (motor-masseter).
Pupillary reflex
Afferent control is CN II. Efferent control is CN III.
Gag reflex
Afferent control is CN IX. Efferent control is CN X.
CN V motor lesion
Causes jaw to deviate toward the side of the lesion due to unopposed force from the opposite pterygoid muscle.
CN X lesion
Causes uvula to deviate away from the side of the lesion. Weak side collapses and uvula points away.
CN XI lesion
Causes weakness in the sternocleidomastoid muscle reducing ability in turning head to contralateral side of lesion. Also causes weakness in trapezius muscle leading to shoulder droop on side of lesion.
CN XII lesion (LMN)
Causes the tongue to deviate toward the side of the lesion (lick your wounds) due to weakened tongue muscles on affected side.
Cavernous sinus
Collection of venous sinuses on either side of pituitary. Blood from the eye and superficial cortex drains to the cavernous sinus than to the internal jugular vein. CN III, IV, V1, VI, and occasionally V2 plus post-ganglionic sympathetic pupillary fibers en route to orbit all pass through cavernous sinus. The cavernous portion of the internal carotid artery is also here. Nerves that control extraocular muscles (plus V1 and V2) pass through the cavernous sinus.
Cavernous sinus syndrome
It presents with variable ophthalmoplegia, a decrease in corneal sensation, Horner syndrome, and occasional decreased maxillary sensation. It occurs secondary to pituitary tumor mass effect, carotid- cavernous fistula, or cavernous sinus thrombosis related to infection. CN VI is most susceptible to injury.
Outer ear physiology
Visible portion of ear (pinna), includes auditory canal and eardrum. It transfers sound waves via vibration of eardrum.
Middle eardrum physiology
Air filled space with three bones called the ossicles (malleus, incus, and stapes). Ossicles conduct and amplify sound from eardrum to inner ear.
Inner ear physiology
Snail shaped, fluid filled cochlea that contains a basilar membrane that vibrates secondary to sound waves. The vibration is than transduced via specialized hair cells transforming it into an auditory nerve signal, which is carried to the brain stem. Each frequency leads to a vibration at a specific location on the basilar membrane (tonotopy): low frequency is heard at the apex near the hicotrema (wide and flexible) and high frequency is heard best at the base of the cochlea (thin and rigid).
Conductive hearing loss
The abnormal rinne test signifies that bone conduction is greater than air. The Weber test localizes to affected ear.
Sensorineural hearing loss
The normal rinne test signifies that air conduction is greater than air. The weber test localizes to unaffected ear.
Noise-induced hearing loss
Damage to the stereociliated cells in the organ of Corti. There is loss of high frequency hearing 1st. Sudden extremely loud noises can produce hearing loss due to tympanic membrane rupture.
Cholesteatoma
Overgrowth of desquamated keratin debris within middle ear space. It may erode ossicles and mastoid air cells causing conductive hearing loss.
UMN facial lesions
Lesion of motor cortex or connection between cortex and facial nucleus. There is contralateral paralysis of lower face. The forehead is spared due to bilateral UMN innervation.
LMN facial lesions
Ipsilateral paralysis of upper and lower face.
Facial nerve palsy
Complete destruction of the facial nucleus itself or its branchial efferent fibers (facial nerve proper). Peripheral ipsilateral facial paralysis with absent forehead creases and drooping smile and an inability to close eye on involved side. It can occur idiopathically (called Bell palsy) with gradual recovery in most cases. It is associated with Lyme disease, herpes simplex and less commonly herpes zoster (Ramsay Hunt syndrome), sarcoidosis, tumors, diabetes. Treatment includes corticosteroids.
Path of facial nerve
Info from the face area of motor cortex (lateral portion) and travels in the corticobulbar tract and decussates and synapses on the upper and lower divisions of the facial nucleus. The upper division also receives input from ipsilateral motor cortex. The facial nerve innervates the ipsilateral side as the nucleus.
Mastication muscles
Three muscles close the jaw including the Masseter, teMoralis, and Medial pterygoid. One opens the lateral pterygoid. All are innervated by the trigeminal nerve (V3). M’s Munch. Lateral Lowers (when speaking of pterygoids with respect to jaw motion). “It takes more muscle to keep your mouth shut.”
Aqueous humor pathway
Aqueous humor is a thin, gelatinous fluid that fills in the anterior and posterior chambers of the eye. It is secreted by the ciliary epithelium, which overlies the ciliary body. Aqueous humor takes a distinct pathway as it moves through the eye: It is secreted into the posterior chamber of the eye. It moves from the posterior chamber to the anterior chamber by moving between the lens and iris and then out through the pupil. It then moves through the trabecular meshwork, the primarily outflow tract for aqueous humor. The trabecular meshwork drains into Schlemm’s Canal, a narrow channel that deliver aqueous humor to the vascular system via the anterior ciliary veins
Three layers of the eye
Outer most is the sclera, middle is the choroid, and inner is the retina.
Structures in the anterior segment of the eye
The outer most structure is the cornea. The iris and cillary bodies (which are attached to the lens) are in the middle structure. The vitreous chamber fills the eye.
Structures in the retina
Optic disk (physiological blind spot), Macula, Fovea centralis, Retinal artery and vein
Hyperopia
Eyes too short for refractive power of the cornea and lens causing light to be focused behind the retina.
Myopia
Eyes are too long for refractive power of the cornea and lens causing light to be focused in front of the retina.
Astimatism
Abnormal curvature of the cornea causing there to be a different refractive power at different axes.
Presbyopia
Age related impaired accommodation (focusing on near objects), possibly due to decreased lens elasticity. It is often necessitates reading glasses.
Cataract
Painless, often bilateral, opacification of lens causing a decreasing in vision. Risk factors include increased age, smoking, EtOH, excessive sublight, prolonged corticosteroid use, classic galactosemia, galactokinase deficiency, diabetes mellitus (sorbitol), trauma, infection.
Glaucoma
Optic disc atrophy with characteristic cupping (thinning of out rim of optic nerve head)
Open angle glaucoma
It is associated with increase age, African-American race, and family history. It is painless and is more common than closed angle in the US. Primary cause is idiopathic. Secondary cause is a blocked trabecular meshwork from WBCs (eg uveitis), RBCs (eg vitreous hemorrhage), retinal elements (eg retinal detachment).
Closed/ narrow angle glaucoma
Primary is caused by enlargement is enlargement or forward movement of lens against central iris (pupil margin), causing obstruction of normal aqueous flow through pupil causing fluid to build up behind the iris, pushing peripheral iris against cornea and impeding flow through trabecular meshwork. Secondary causes include hypoxia from retinal disease (eg diabetes mellitus, vein occlusion) induces vasoproliferation in iris that contracts angle.
Chronic closed angle glaucoma
It is often asymptomatic with damage to optic nerve and peripheral vision.
Acute closed angle glaucoma
This is a true ophthalmic emergency. An increase in IOP pushes the iris forward causing the angle to close abruptly. Presents as a very painful, red eye, sudden vision loss, halos around lights, rock-hard eye, frontal headache. Do not give epinephrine because of its mydriatic (dilation of the pupil) effect.
Uveitis
Inflammation of uvea (eg iritis aka anterior uveitis, choroiditis aka posterior uveitis). There may be hypopyon (accumulation of pus in anterior chamber) or conjunctival redness. It is associated with systemic inflammatory disorders (eg sarcoidosis, rheumatoid arthritis, juvenile idiopathic arthritis, HLA-B27 associated conditions.
Age related macular degeneration
Degeneration of the macula (central area of the retina). It causes distortion (metamorphopsia) and eventual loss of central vision (scotomas). It can be either dry or wet.
Dry age related macular degeneration
Non exudative, includes over 80% of age related macular degeneration. There is deposition of yellowish extracellular material in and beneath Bruch membrane (innermost layer of the choroid) and retinal pigment epithelium (called drusen) with a gradual decrease in vision. Progression can be prevented with multivitamin and antioxidant supplements.
Wet age related macular degeneration
Exudative, includes 10-15% of age related macular degeneration. There is rapid loss of vision due to bleeding secondary to choroidal neo-vascularization. Treat with anti-VEGF (vascular endothelial growth factor) injections (eg ranibizumab) or laser.
Diabetic retinopathy
Retinal damage due to chronic hyperglycemia. There are two types: non-proliferative and proliferative. Non-proliferative occurs due to damaged capillaries that leak blood causing lipids and fluid to seep into the retina leading to hemorrhages and macular edema. Treatment includes blood sugar control and macular laser. Proliferative is due to chronic hypoxia that results in new blood vessel formation with resultant traction on the retina. Treatment includes peripheral retinal photocoagulation and anti-VEGF (eg bevacizumab).
Retinal vein occlusion
Blockage of central or branch retinal vein due to compression from nearby arterial atherosclerosis. There is retinal hemorrhage and venous engorgement and edema in affected area.
Retinal detachment
Separation of neurosensory layer of retina (photoreceptor layer with rods and cones) from outermost pigmented epithelium, which normally shields excess light and supports retina. This leads to degeneration of photoreceptors causing vision loss. It may be secondary to retinal breaks, diabetic traction (abnormal blood vessels that pull of the retina), and and inflammatory effusions. It can be visualized on fundoscopy by the splaying and paucity of retinal vessels. This can be correlated with cross-sectional “optical ultrasound”. Breaks are more common in patients with high myopia and are often preceded by posterior vitreous detachment (signs include flashes and floaters) and eventual monocular loss of vision like a curtain drawn down. This is a surgical emergency.
Central retinal artery occlusion
Acute, painless monocular vision loss. Retina is cloudy with attenuated vessels and cherry red spot at the fovea (the center of the macula).
Retinitis pigmentosa
It is a type of inherited retinal degeneration. It causes a painless, progressive vision loss beginning with night blindness (rods affected first). Bone spicule shaped deposits around macula.
Retinitis
Retinal edema and necrosis leading to a scar. It it often due to a viral infection (CMV, HSV, HZV). It is associated with immunosuppression.
Papilledema
Optic disc swelling (usually bilateral) due to an increase in ICP (eg secondary mass effect). Enlarged blind spot and elevated optic disc with blurred margins is seen on fundoscopic exam.
Miosis
Constriction due to parasympathetic control. The 1st neuron travels from the Edinger-Westphal nucleus to ciliary ganglions via CN III. The secondary neuron travels the short ciliary nerves to pupillary sphincter muscles. There is no crossing.
Pupillary light reflex
light in either retina sends signal via CN II to pretectal nuclei in the midbrain that activates bilateral Edinger-Westphal nuclei, leading to pupil contraction bilaterally (consensual reflex). Therefore illumination of one eye results in bilateral pupil constriction.
Mydriasis
Dilation under sympathetic control. The first neuron travels from the hypothalamus to the ciliospinal center of Budge (located between C8-T2). The second neuron exits at T1 and travels to the superior cervical ganglion by traveling along the cervical sympathetic chain near lung apex and subclavian vessels. The third neuron travels along the plexus around the internal carotid, through the cavernous sinus, and enters the orbit as a long ciliary nerve to pupillary dilator muscles. The sympathetic fibers also innervate smooth muscle of eyelids (minor retractors) and sweat glands of forehead and face.
Marcus Gunn pupil
It is an afferent pupillary defect due to optic nerve damage or severe retinal injury, which causes a bilateral decrease in pupillary constriction when light is shone in the affected eye relative to the unaffected eye. It can be tested with the swinging flashlight test. It is seen in MS.
Horner syndrome
Sympathetic denervation of the face causing Ptosis (slight drooping of eyelid due to denervation of the superior trasal muscle), Anhidrosis (absence of sweating) and flushing (rubor) of affected side of face, and Miosis (pupil constriction). (PAM is horny [Horner]) It is associated with a lesion of the spinal cord above T1 (eg Pancoast tumor, Brown Sequard syndrome [cord hemisection], and late stage syringomyelia).
Occular motility
CN VI inntervates the Lateral Rectus. CN IV innervates the Superior Oblique. CN III innervates the Rest. The chemical formula is LR6SO4R3. The superior oblique abducts, intorts, and and depresses while adducted. To test function of each muscle, ask patient to follow a path from primary position (ie SO depression function is best tested when eye is adducted). Obliques go Opposite (left SO and IO tested with patient looking right). IOU: IO tested looking Up.
CN III damage
Occulomotor nerve has both motor (central) and parasympathetic (peripheral) components. Motor output to ocular muscles is affected primarily by vascular disease (eg diabetes mellitus from glucose getting converted to sorbitol) due to a decrease in diffusion of oxygen and nutrients to the inferior fibers from compromised vasculature that resides on outside of nerve. Signs include ptosis and down and out gaze. Parasympathetic output fibers on the periphery are the first affected by compression (eg posterior communicating artery aneurysm, uncal herniation). Signs include diminished or absent pupillary light reflex called a “blown pupil” and is often associated with a “down and out” gaze.
CN IV damage
Superior oblique damage causes eye to move 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).
CN VI damage
Lateral rectus damage cause medially directed eye that cannot abduct.
Visual field defects
Types include unilateral anopia, bitemporal hemianopia (pituitary lesion and chiasm), left homonysmous hemianopia (visual field loss on the same side of both eyes), left upper quadrantic anopia (right temporal lesion and middle cerebral artery), left lower quadrantic anopia (right parietal lesion and MCA), left hemianopia with macular sparing (PCA infarct, macula causes bilateral projection to occiput), and central scotoma (macular degeneration).
Meyer loop
Upper quadrantic anopia describes a loss of half of the upper visual fields (either right or left) of both eyes. It is caused by damage to the contralateral ventral optic radiations (Meyer’s loop of the temporal lobe, which contain fibers from the inferior temporal retinal quadrant of the ipsilateral eye, and the inferior nasal retinal quadrant of the contralateral eye. Lesions or tumors of the temporal lobe have the potential to damage Meyer’s Loop, resulting in upper quadrantic anopia of the contralateral visual field. Meyer’s loop loops around inferior horn of lateral ventricle.
Dorsal optic radiation
Lower quadrantic anopia describes a loss of half of the lower visual fields (either right or left) of both eyes. It is caused by damage to the contralateral dorsal optic radiations of the parietal lobe, which contain fibers from the superior temporal retinal quadrant of the ipsilateral eye, and the superior nasal retinal quadrant of the contralateral eye.
Medial longitudinal fasciculus (MLF)
A pair of tracts that allows for crosstalk between CN VI and CN III nuclei. Coordinates both eyes to move in the same horizontal direction. It is highly myelinated so that eyes can communicate quickly at same time. Lesions may be unilateral or bilateral (latter classically seen in multiple sclerosis). When looking left, the left nucleus of CN VI fires, which contracts the left lateral rectus and stimulates the contralateral (right) nucleus of CN III via the right MLF to contract the right medial rectus. Directional term (eg right INO or left INO) refers to which eye is paralyzed.
Lesions in the MLF
Causes internuclear ophthalmoplegia (INO), a conjugate horizontal gaze palsy. There is a lack of communication such that when CN VI nucleus activates ipsilateral lateral rectus, the contralateral CN III nucleus does not stimulate medial rectus to fire. Abducting eye gets nystagmus (CN VI overfires to stimulate CN III). Convergence is normal.
Dementia
There is a decrease in cognitive ability, memory, or function with intact consciousness.
Alzheimer disease
It is the most common cause of dementia in the elderly. Down syndrome patients have an increase risk of developing Alzheimer. Familial form (10% of cases) are associated with the following altered proteins: apoE2 (decreases risk), apoE4 (increases risk), and APP, presenilin-1, presenilin-2 (increase risk of early onset). There is widespread cortical atrophy. There is also narrowing gyri and widening of sulci. ACh decreases. Senile plaques are seen in grey matter due to extracellular beta-amyloid core, which could also cause amyloid angiopathy, increasing intracellular hemorrhage. A-beta (amyloid-beta) is synthesized by cleaving amyloid precursor protein (APP). Neurofibrillary tangles are due to intracellular hyperphosphorylated tau protein, which are insoluble cytoskeletal elements. The number of tangles correlates with the degree of dementia.
Frontotemporal dementia
Causes dementia, aphasia, parkinsonian aspects, and a change in personality. It spare the parietal lobe and the posterior 2/3 of the superior temporal gyrus. It is also called Pick disease. Pick bodies are tau protein aggregates that can be seen on silver staining. There is frontotemporal atrophy.
Lewy body dementia
It initially causes dementia and visual hallucinations, followed by parkinsonian features. There are alpha-synuclein defect (Lewy bodies, primarily in the cortical region).
Other causes of dementia
Multi-infarct (aka vascular, 2nd most common cause of dementia in the elderly), syphilis, HIC, vitamin B1, B3, or B12 deficiency, wilson disease, normal pressure hydrocephalus.
Creutzfeldt-Jakob disease
Rapidly progressive (weeks to months) dementia with myoclonus (startle myoclonus). Spongiform cortex. Prions are made of beta pleated sheet that are resistant to proteases.
Multiple sclerosis
Autoimmune inflammation and demyelination of the CNS (brain and spinal cord). Patients can present with optic neuritis (sudden loss of vision resulting in Marcus Gunn pupils), internuclear ophthalmoplegia (INO), hemiparesis, hemisensory symptoms, bladder/ bowel incontinence. Relapsing and remitting course. Most often affects women in their20s and 30s. It is most common in whites living further from the equator. Charcot classic triad of MS is a SIN: Scanning speech, Intention tremor (also Incontinence and Internuclear ophthmalmoplegia), Nystagmus.
Multiple sclerosis findings
An increase in protein (IgG) in CSF. Oligoclonal bands are diagnostic. MRI is gold standard. Periventricular plaques (area of oligodendroctye loss and and reactive gliosis, with destruction of axons. Multiple white matter lesions separated in space and time.
Multiple sclerosis treatment
There is slowed progression with disease modifying therapies (eg beta-interfereon, natalizumab). Treat acute flares with IV steroids. Symptomatic treatment for neurogenic bladder (catheterization, muscarinic antagonists), spasticity (baclofen, GABAb receptor agonists), pain (opioids),
Acute inflammatory demyelinating polyradiculopathy
It is the most common subtype of Guillain Barre syndrome. It is an autoimmune condition that destroys Schwann cells causing inflammation and demyelination of peripheral nerves and motor fibers, resulting in symmetric ascend muscle weakness and paralysis that begins in the lower extremities. Facial paralysis occurs in 50% of cancer. There may be autonomic dyregulation (eg cardiac irregularities, hypertension, hypotension) or sensory abnormalities. Almost all patients survive with the majority recovering completely within weeks or months. CSF findings show an increase in protein with normal cell count (albuminocytologic dissociation). The increase in protein may cause papilledema. It is associated with infections (eg Campylobacter jejuni and viral), causing an autoimmune attack of peripheral myelin due to molecular mimicry, inoculation, and stress but no definitive link to pathogens. Respiratory support is critical until recovery. Additional treatment include plasmapheresis and IV immunoglobulins.
Acute disseminated (postinfectious) encephalomyelitis
Multifocal periventricular inflammation and demyelination after infection (commonly the measles or VZV) or certain vaccinations (eg rabies and smallpox).
Charcot Marie Tooth disease
Also known as hereditary motor and sensory neuropathy (HMSN). A group of progressive hereditary nerve disorders related to the defective production of proteins involved in the structure and function of peripheral nerves of the myelin sheath. Typically autosomal dominant inheritance pattern and associated with scoliosis and foot deformities (high or flat arches).
Krabbe disease
Autosomal recessive lysosomal storages due to deficiency of galactocerebrosides. Build up of galactocerebroside and psychosine destroys myelin sheath. Findings include peripheral neuropathy, developmental delay, optic atrophy, and globoid cells (a large cell of mesodermal origin that is found clustered in the intracranial tissues).
Metachromatic leukodystrophy
Autosomal recessive lysosomal storage disease that is most commonly due to arylsulfatase A deficiency. It can cause buildup of sulfatides causing impairment of the production and destruction of the myelin sheath. Findings include central and peripheral demyelination with ataxia and dementia.
Progressive multifocal leukoencephalopathy
Demyelination of CNS due to destruction of oligodendrocytes. It is associated with JC virus. It is seen in 2-4% of AIDS patients (reactivation of latent viral infections.) It is rapidly progressive, usually fatal. There is an increase risk associated with natalizumab.
Adrenoleukodystrophy
It is x-linked genetic disorder typically affecting males. It disrupts metabolism of very long chain fatty acids creating excessive buildup in the nervous system, adrenal gland, and testes. This progressive disease that can lead to long term coma/death and adrenal gland crisis.
Partial (focal) seizures
They affect a single area of the brain, most commonly they originate in medial temporal lobe. It is often preceded by seizure aura. It can secondarily generalize. Types include simple partial and complex partial.
Simple partial seizures
Consciousness intact, affecting motor, sensory, autonomic, and psychic. When consciousness is maintained, the seizure is described as focal seizure without impairment of consciousness. When consciousness is not maintained, the seizure is described as focal seizure with impaired consciousness
Complex partial seizures
Complex partial seizures differ from simple partial seizures only in that the patient will lose or have altered consciousness. First-line therapy for both simple partial and complex partial seizures is carbamazepine.
Generalized seizures
They are diffuse. Types include absence, myoclonic, tonic-clonic, tonic, atonic.
Absence (petit mal)
Absence seizures are a type of generalized seizure that often occur in children. They present as a blank stare with no postictal confusion and often occur multiple times per day. The characteristic finding on electroencephalogram (EEG) in absence seizures is 3-Hz spike-and-slow-wave complexes. First-line therapy for absence seizures is ethosuximide.
Myoclonic
Myoclonic seizures are a type of generalized seizure and are characterized by quick, repetitive jerks of the body or extremities. The first-line therapy for myoclonic seizures is valproic acid.
Tonic- clonic (grand mal)
Tonic-Clonic (grand mal) seizures are generalized and a type of generalized seizure and are characterized by an alternating cycle where the patient is tonic (stiff) and then becomes clonic (jerking movements). The three first-line therapies for tonic-clonic seizures can be remembered by “PVC”: Phenytoin , Valproic acid, Carbamazepine.
Tonic seizure
Generalized seizure, which are characterized just by stiffening of the body
Atonic seizure.
Atonic or “drop seizures” (patient falls to the floor), which are generalized and often confused with syncope.
Epilepsy
A disorder of recurrent seizures (febrile seizures are not epilepsy).
Status epilepticus
Status epilepticus is defined as > 10-30 minutes of either: Continuous seizure activity OR Recurrent seizures without recovery (return to baseline) between seizures. This is a medical emergency due to the persistent seizure activity in the brain. . First-line therapy for status epilepticus is benzodiazepines, such as diazepam. Causes by age include: children-genetic, infection (febrile), trauma, congenital, metabolic; adults- tumor, trauma stroke, infection, elderly- stroke, tumor, trauma, metabolic, and infection.
Cluster headaches
Cluster headaches are a type of chronic headache that occurs at the same time each day, which occur for days to weeks. The clusters of painful headache episodes are separated by periods of remission. Cluster headaches are associated with ipsilateral autonomic symptoms (ptosis, miosis, lacrimation, rhinorrhea, etc…). Males are more likely to have cluster headaches than females. The pathogenesis of cluster headaches is poorly understood, but it is thought to be due to extracerebral causes. Symptoms of cluster headaches include severe unilateral periorbital pain. The pain is described as a boring or drilling sensation. Cluster headaches are often associated with horner syndrome (which includes ptosis, miosis, and anhidrosis), lacrimation, and nasal congestion. They can last from 30 minutes to 3 hours and can often occur during sleep. DDx includes trigeminal neuralgia, which produces repetitive shooting pain in the distribution of CN V that lasts (typically) for less than a minute.
Treatment for cluster headaches
Abortive treatment of cluster headaches includes: High flow 100% oxygen and sumatriptan are first line therapy, Ergotamine, dihydroergotamine, Intranasal lidocaine. Cluster headache prophylaxis includes the use of: Verapamil is first line, Ergotamine, dihydroergotamine, Glucocorticoids, such as prednisone and dexamethasone, Lithium, Topiramate.
Tension headaches
Tension headaches are a diffuse, mild to moderate headache that is often described as feeling like there’s a tight band around the head. It is the most common type of headache. Tension headaches affect females more often than males. Factors that precipitate tension headaches include stress and fatigue. Pain from tension headaches is usually bilateral (unlike migraines and cluster headaches), with a feeling of tightness and occipital or neck pain. It is also associated with anxiety. Unlike migraines and cluster headaches, tension headaches have a variable duration.
Treatment of tension headaches
Treatment of tension headaches includes: NSAIDs, Amitriptyline, Ergotamine, dihydroergotamine, Sumatriptan, zolmitriptan, Relaxation exercises
Migraine headache
Migraines are severe, throbbing headaches, often unilateral, that may be accompanied by other symptoms such as nausea, vomiting, photophobia (sensitivity to lights), and phonophobia (sensitivity to noise), flushing, tearing, and rhinorrhea. People that suffer migraines are often 10-30 years of age, with females affected more commonly than males. Migraine with aura (a.k.a. classic migraine) are severe headaches preceded by a visual change such as bright or flashing lights, dark spots occluding areas of vision (scotomas), visual field changes, and even focal neurological deficits such as hemiparesis. Auras typically last for 10-20 minutes. Migraine without aura (a.k.a. common migraine) are severe headaches that are not preceded by an aura. Most cases of migraines do not involve an aura.Migraines can last anywhere from 4-72 hours.
Migraine treatment
Migraine treatment consists of: NSAIDs (chronic NSAID use for treatment/prophylaxis can cause migraine headaches), Ergotamine, dihydroergotamine, Selective serotonin agonists (5-HT1B, 5-HT1D) such as Sumatriptan, zolmitriptan, IV antiemetics, such as metoclopramide, chlorpromazine. Migraine prophylaxis includes the use of: Tricyclic antidepressant such as amitriptyline, Beta blockers such as metoprolol, propranolol, and timolol, Calcium channel blockers such as nifedipine and verapamil, Valproate, Topiramate
Other causes of headaches
Other causes of headache include subarachnoid hemmorrhage (“worst headache of my life”), meningitis, hydrocephalus, neoplasia, and arteritis.
Vertigo
Sensation of spinning wile actually stationary. Subtupes of dizziness, but distenct from lightheadedness.
Peripheral vertigo
The more common version. It occurs due to inner ear etiology (eg semicircular canal debris, vestibular nerve infection, Meniere disease). Postitional testing, causes delayed horizontal nystagmus.
Central vertigo
Brain stem or cerebellar lesion (eg stroke affecting vestibular nuclei or posterior fossa tumor). Findings include directional change of nystagmus, skew deviation, diplopia, dysmetria. Positional testing shows immediate nystagmus in any direction and may change directions. There are focal neurologic findings.
Sturge Weber syndrome
Congenital, non-inherited (somatic), developmental anomaly of neural crest derivatives (mesoderm/ extoderm) due to activating mutation of GNAQ gene. Affects small (capillary-sized) blood vessels, which causes a port-wine stain of the face (nevus flammeus, a non-neoplastic birthmark in CN V1/V2 distribution). There is also ipsilateral leptomeingeal angioma causing seizure/epilepsy. There is also intellectual disability. Episcleral hemangioma causes there to be an increase in IOP, leading to early onset glaucoma. STURGE-weber: Sporadic, port-wine Stain, Tram track calcification (opposing gyri), Unilateral, Retardation (intellectual disability), Glaucoma, GNAQ gene, and Epilepsy.
Tuberous sclerosis
HAMARTOMAS: Hamartomas in the CNS and skin, Angiofibromas, Mitral regurgitation, Ash-leaf spots, cardiac Rhabdomyoma, Tuberous sclerosis, autosomal dOminant, Mental retardation (intellectual disability), renal Angiomyolipoma, Seizures, Shagreen patches. There is an increase incidence of subependyma astrocytomas and ungual fibromas.
Neurofibromatosis type I (von Recklinghausen disease)
Cafe-au-lait spots, Lisch nodules (pigmented iris hamartomas), cutaneous neurofibromas, optic gliomas, pheochromocytomas. It is caused by mutated NF1 tumor suppressor gene (neurofibromin, a negative regulator of RAS) on chromosome 17. Skin tumors of NF-1 are derived from neural crest cells.
von Hippel Lindau disease
Hemangioblastomas (high vascularity with hyper chromatic nuclei) in retina, brain stem, cerebellum, spine. There are also also angiomatosis (eg cavernous hemangiomas in skin, mucosa, organs), bilateral renal cell carcinomas, and pheochromocytomas.
Glioblastoma multiforme (grade IV astrocytoma)
An adult primary tumor. A common, highly malignant primary brain tumor with about a one year median survival. It is found in the cerebral hemispheres. It can cross corpus callosum (butterfly glioma). It will stain for GFAP. Histology shows pseudopalisading pleomorphic tumor with border central areas of necrosis and hemorrhage.
Meningioma
An adult primary tumor. It is common and typically a benign primary tumor. It most often occurs in convexities of hemispheres (near surfaces of the brain) and parasagittal region. It arises from arachnoid cells and is extra axial (external to brain parenchyma), and may have a dural tail. It is often asymptomatic and may present with seizures or focal neurologic sign. It can be treated with resection and/ or radiosurgery. Histology will show spindle cells concentrically arrange in a whorled pattern and psammoma bodies (laminated calcifications).
Hemangioblastoma
An adult primary tumor. It is most often cerebellar. It is associated with von Hippel Lindau syndrome when found with retinal angiomas. It can produce erythropoietin leading to secondary polycythemia. Histology will show closely arranged, thin walled capillaries with minimal intervening parenchyma.
Schwannoma
An adult primary tumor. It is classically at the cerebellopontine angle, but it can present along any peripheral nerve. Schwann cell in origin and S-100 positive. It is often localized to CN VIII, creating a vestibular schwannoma. Resectable or treated with stereotactic radiosurgery. Bilateral vestibular schwannomas found in NF-2.
Oligodendroglioma
An adult primary tumor. It is relatively rare and slow growing. It is most often found in the frontal lobes with a chicken-wire pattern. On histology will show oligodendrocytes, which look like fried egg cells due to their round nuclei with clear cytoplasm. It is often calcified.
Pituitary adenoma
An adult primary tumor. It is most commonly a prolactinoma. It causes bitemporal hemianopia due to pressure of the optic chiasm. There can be hyper or hypo pituitary sequelae.
Pilocytic (low-grade) astrocytoma
A childhood primary brain tumor. It is usually well circumscribed. In children, it is most often found in the posterior fossa (eg cerebellum). It may be supratentorial. GFAP positive. It is benign and has a good prognosis. Histology will show Rosenthal fibers, which are eosinophilic and corkscrew fibers.
Medulloblastoma
A childhood primary brain tumor. It is a highly malignant cerebellar tumor, a form of primitive neuroectodermal tumor. It can compress the 4th ventricle, causing hydrocephalus. It can send “drop metastases” to spinal cord. Histology shows Homer- Wright rosettes and solid (gross), small blue cells.
Ependymoma
A childhood primary brain tumor. They are an ependymal cell tumor that is most commonly fount in the fourth ventricle. It can cause hydrocephalus. There is a poor prognosis. Histology will show characteristic perivascular rosetts and rod shaped blepharoplasts (basal ciliary bodies) found near nucleus.
Craniopharyngioma
A childhood primary brain tumor. It is a benign tumor that may be confused with pituitary adenoma (both can cause bitemporal hemianopia). It is the most common childhood supratentorial tumor. It is derived from remnants of Rathke pouch. Calcification is common, which looks like tooth enamel-like.
Cingulate (subfalcine) herniation under falx cerebri
It can compress the anterior cerebral artery.
Downward transtentorial (central) herniation
A caudal displacement of brain stem, which can cause a rupture of paramedian basilar artery branches causing Duret hemorrhages (small lineal areas of bleeding in the midbrain and upper pons). It is usually fatal.
Uncal herniation
Uncus is the medial temporal lobe that can lead to compression of the ipsilateral CN III (blown pupil, down and out gaze), ipsilateral PCA (causing contralateral homonymous hemianopia), contralateral crus cerebri at the Kernohan notch (ipsilateral homonymous hemianopia) (ipsilateral paresis and a false localization sign). Neurological signs are described as “false localizing” if they reflect dysfunction distant or remote from the expected anatomical location of pathology.
Cerebellar tonsillar herniation into the foramen magnum
Causes coma and death due to compression of the brain stem.
Epinephrine application towards glaucoma
An alpha 1 agonist that causes a decrease in aqueous humor synthesis via vasoconstriction. Side effects include mydriasis, and therefore should not be used with closed-angle glaucoma. Use would lead to further closing of the trabecular meshwork (via narrowing of the uveoscleral outflow tract) leading to decreased flow of aqueous humor. Other side affects include blurry vision, ocular hyperemia, foreign body sensation, ocular allergic reactions, and ocular puritus.
Brimonidine application towards glaucoma
An alpha 2 agonist that causes a decrease in aqueous humor synthesis. Side effects include blurry vision, ocular hyperemia, foreign body sensation, ocular allergic reactions, and ocular puritus.
Timolol application towards glaucoma
A beta blocker that decreases aqueous humor synthesis. There is no pupillary or vision changes.
Betaxolol application towards glaucoma
A beta blocker that decreases aqueous humor synthesis. There is no pupillary or vision changes.
Carteolol application towards glaucoma
A beta blocker that decreases aqueous humor synthesis. There is no pupillary or vision changes.
Acetazolamide application towards glaucoma
A diuretic that decreases aqueous humor synthesis via inhibition of carbonic anhydrase. There are no pupillary or vision changes.
Pilocarpine application towards glaucoma
A direct cholinomimetics that increases outflow of aqueous humor via contraction of ciliary muscle and opening of trabecular meshwork. Pilocarpine is used in emergencies as it is very effective at opening meshwork into the canal of Schlemm. Side effects include miosis and cyclospasm (contraction of ciliary muscles).
Carbachol application towards glaucoma
A direct cholinomimetics that increases outflow of aqueous humor via contraction of ciliary muscle and opening of trabecular meshwork. Side effects include miosis and cyclospasm (contraction of ciliary muscles).
Physostigmine application towards glaucoma
An indirect cholinomimetics that increases outflow of aqueous humor via contraction of ciliary muscle and opening of trabecular meshwork. Side effects include miosis and cyclospasm (contraction of ciliary muscles).
Echothiophate application towards glaucoma
An indirect cholinomimetics that increases outflow of aqueous humor via contraction of ciliary muscle and opening of trabecular meshwork. Side effects include miosis and cyclospasm (contraction of ciliary muscles).
Latanoprost application towards glaucoma
A prostaglandin (PGF 2alpha) that increases outflow of aqueous humor. It can cause darkening of the iris (browning).
Opioid analgesics
Includes morphine, fentanylm codein, loperamide, methadone, meperidine, dextromethorphan, diphenoxylate, pentazosine. They act as agonists as opioid receptors (morphine= mui, gamma=enkephalin, kappa=dynorphin). to modulate synaptic transmission to open K channels and close Ca channels, causing a decrease in synaptic transmission through inhibiting the release of ACh, norepinephrine, 5-HT, glutamate, and substance P.
Opioid clinical use
They are used for pain, cough suppression (destromethorphan, diarrhea (loperamide, diphenoxylate), acute pulmonary edema, maintenance programs for heroin addicts (methadone, buprenorphine with naloxone).
Opioid toxicity
Can lead to addiction, respiratory depression, constipation, miosis (pinpoint pupils), additive CNS depression with other drugs. Tolerance does not develop to miosis and constipation. Toxicity is treated with naloxone or naltrexone (opioid receptor antagonist).
Butorphanol
A kappa opioid receptor agonist and mui opioid receptor partial agonist thereby producing analgesia. It is used with severe pain (eg migraine or labor). It causes less respiratory depression than full opioid agonists. It can cause opioid withdrawal symptoms if patient is also taking full opioid agonist (competition for opioid receptors). Overdose is not easily reversed with naloxone.
Tramadol
A very weak opioid agonist that also inhibits 5-HT and norepinephrine reuptake (through working on multiple neurotransmitters- “tram it all in tramadol”). It is used to treat chronic pain. Toxicity is similar to opioids. It also decreases seizure threshold and can cause serotonin syndrome.
Medications to treat simple partial seizures
Carbamazepine (first line), phenytoin, valproic acid, gabapentin, phenobarbital, topiramate, lamotrigine, levetiracetam, tiagabine, and bigabatrin
Medications to treat complex partial seizures
Carbamazepine (first line), phenytoin, valproic acid, gabapentin, phenobarbital, topiramate, lamotrigine, levetiracetam, tiagabine, and bigabatrin
Medications to treat tonic-clonic seizures
First line therapies include phenytoin, carbamazepine, and valproic acid. Other treatments include phenobarbital, topiramate, lamotrigine, levetiracetam.
Medications to treat absence seizures
First line treatment is ethosuximide. Other therapies include valproic acid and lamotrigine.
Medications to treat status epilepticus seizures
First line acute therapy are benzodiazepines (diazepam or lorazepam). First line preventative therapy is phenytoin.
Ethosuximide applications
First line treatment for absence seizures (Sucks to have Silent Seizures).
Ethosuximide mechanism
It works by blocking thalamic T-type Ca channels
Ethosuximide side effects
GI, fatigue, headache, urticaria, Stevens-Johnson syndrome. EFGHIJ: Ethosuximide causes Fatigue, GI distress, Headache, Itching, and stevens Johnson syndrome.
Phenytoin applications
First line treatment for tonic-clonic and status epilepticus (prophylaxis). Also used for treating both simple and complex seizures. Use fosphentoin for parenteral use.
Phenytoin mechanism
Increases Na channel inactivation. It is zero order kinetics.
Phenytoin side effects
Nystagmus, diplopia, ataxia, sedation, gingival hyperplasia, hirsutism, peripheral neuropathy, magaloblastic anemia, teratogenesis (fetal hydantoin syndrome), SLE-like syndrome, induction of cytochrome P 450, lymphadenopathy, Stevens Johnson syndrome, osteopenia.
Carbamazepine applications
First line treatment for simple and complex partial seizures and tonic clonic seizure. It is also first line treatment for trigeminal neuralgia.
Carbamazepine mechanism
Increases Na channel inactivation.
Carbamazepine side effects
Diplopia, ataxia, blood dyscrasias (agranulocytosis, aplastic anemia), liver toxicity, teratogenesis, induction of cytochrome P 450, SIADH, Stevens Johnson syndrome.
Valproic acid application
First line treatment for tonic clonic seizure. It is also used to treat simple and complex partial seizures and absence seizures. It is also used to treat myoclonic seizures and bipolar disorder.
Valproic acid mechanism
Increases Na channel inactivation, increases GABA concentration by inhibiting GABA transaminase.
Valproic acid side effects
GI, distress, rare but fatal hepatotoxicity (measure LFTs), neural tube defects (eg spina bifida), tremor, weight gain, contraindicated in pregnancy.
Gabapentin application
Treats simple and complex partial seizure. It is also used for peripheral neuropathy and postherpetic neuralgia.
Gabapentin mechanism
It primarily inhibits high-voltage activated Ca channels. It is a designed as GABA analog.
Gabapentin side effects
sedation and ataxia
Topiramate applications
It is used to treat simple and complex partial seizures and tonic clonic seizures. It is also used in migraine prevention
Topiramate mechanism
It blocks Na channels and increases GABA action.
Topiramate side effects
sedation, mental dulling, kidney stones, and weight loss
Lamotrigine application
It is used to treat simple and complex partial seizures, tonic clonic seizures, and absence seizures.
Lamotrigine mechanism
blocks voltage gated Na channels
Lamotrigine side effects
Stevens Johnson syndrome (must be titrated slowoly)
Levetiracetam application
It is used to treat simple and complex partial seizures and tonic clonic seizures.
Levetiracetam mechanism
Unknown, it may modulate GABA and glutamate release.
Tiagabine application
It is used to treat simple and complex partial seizures.
Tiagabine mechanism
Increases GABA by inhibiting reuptake.
Vigabatrin application
It is used to treat simple and complex partial seizures.
Vigabatrin mechanism
Increases GABA by irreversibly inhibiting GABA transaminase.
Seizure medication that causes Stevens-Johnson syndrome
It is a prodrome of malaise and fever followed by rapid onset of erythematous/ purpuric macules (oral, ocular, and genital). Skin lesions progress to epidermal necrosis and sloughing. Drugs that cause this include ethosuximde, phenytoin, carbamazepine, and lamotrigine.
Barbiturates
Includes phenobarbital, pentobarbital, thiopental, and secobarbital. They facilitate GABAa action by increasing duration of Cl channel opening, thus decreasing neuron firing (barbiDURATes increases DURATion). It is used as a sedative for anxiety, seizures, insomnia, induction of anesthesia (thiopental). It can cause respiratory and cardiovascular depress, which can be fatal, CNS depression (can be exacerbated by EtOH use), depends, drug interactions (induces p-450). Overdose treatment is supportive (assist respiration and maintain BP).
Benzodiazepines
Diazepam, lorazepam, triazolam, temazepam, ocazepam, midazolam, chlordiazepoxide, alprazolam. Benzodiazepines (diazepam, lorazepam, triazolam, temazepam, oxazepam, midazolam, chlordiazepoxide, alprazolam) work by potentiating the effect of GABA by increasing the frequency of chloride channel opening. Thus, these drugs are ineffective in the absence of GABA. (Frenzodiazepines increase the frequency.) Short-acting benzodiazepines have a higher addictive potential. Benzodiazepines are the first line agents to treat alcohol withdrawal, which is known as Delirium Tremens (DTs) if the withdrawal is severe. Benzodiazepines are the first line agents for status epilepticus. Additional indications for benzodiazepines include: Anxiety, Spasticity, Night terrors and sleepwalking, Insomnia. Use as a general anesthetic. Toxicities of benzodiazepines include: Sedation, Respiratory depression (although less risk than with barbiturates), Tolerance/dependence
Nonbenzodiazepine hypnotics
Nonbenzodiazepine hypnotics/”The ZZZs Drugs” (Zolpidem, Zaleplon, Eszopiclone) agonize the Alpha-1 subtype of the GABA receptor to induce sleepiness for insomnia patients. Please note that the receptor is sometimes referred to as the BZ1 subtype of the GABA receptor. Notable side effects of nonbenzodiazepine hypnotics include headaches, ataxia, and confusion. Nonbenzodiazepine hypnotics have a shorter duration of action than previous hypnotic agents. Therefore, they only cause modest psychomotor depression, few amnestic effects, and have less risk of dependence.
Potency of anesthetics
CNS drugs must be lipid soluble (cross the blood-brain barrier) or can be actively transported. Drugs with a decrease solubility in blood= rapid induction and recovery times. Drugs with an increase solubility in lipids = an increase in potency = 1/minimal alveolar concentration (MAC)
Minimal alveolar concentration (MAC) of inhaled anesthic
It is the concentration that is required to prevent 50% of subjects from moving in response to noxious stimulus (eg skin incision). For example N2O has a decrease in blood and lipid solubility and thus has a fast induction and low potency. Halothane, in contras, has a high lipid and blood solubility, and thus has a high potency and slow induction.
Halothane
An inhaled anesthetic with unknown mechanism. Effects include myocardial depression, respiratory depression, nausea/ emesis, an increase in cerebral blood flow (a decrease in cerebral metabolic demand). Toxicities include hepatotoxicity, and malignant hyperthermia, a rare, life threatening hereditary condition in which inhaled anesthetics and succinylcholine induce fever and severe muscle contraction. Treatment of dantrolene.
Enflurane
An inhaled anesthetic with unknown mechanism. Effects include myocardial depression, respiratory depression, nausea/ emesis, an increase in cerebral blood flow (a decrease in cerebral metabolic demand). Toxicities include being a pro-convulsent and cause malignant hyperthermia, a rare, life threatening hereditary condition in which inhaled anesthetics and succinylcholine induce fever and severe muscle contraction. Treatment of dantrolene.
Isoflurane
An inhaled anesthetic with unknown mechanism. Effects include myocardial depression, respiratory depression, nausea/ emesis, an increase in cerebral blood flow (a decrease in cerebral metabolic demand). It can cause malignant hyperthermia, a rare, life threatening hereditary condition in which inhaled anesthetics and succinylcholine induce fever and severe muscle contraction. Treatment of dantrolene.
Sevoflurane
An inhaled anesthetic with unknown mechanism. Effects include myocardial depression, respiratory depression, nausea/ emesis, an increase in cerebral blood flow (a decrease in cerebral metabolic demand). It can cause malignant hyperthermia, a rare, life threatening hereditary condition in which inhaled anesthetics and succinylcholine induce fever and severe muscle contraction. Treatment of dantrolene.
Sevoflurane
An inhaled anesthetic with unknown mechanism. Effects include myocardial depression, respiratory depression, nausea/ emesis, an increase in cerebral blood flow (a decrease in cerebral metabolic demand). It can cause malignant hyperthermia, a rare, life threatening hereditary condition in which inhaled anesthetics and succinylcholine induce fever and severe muscle contraction. Treatment of dantrolene.
Methoxyflurane
An inhaled anesthetic with unknown mechanism. Effects include myocardial depression, respiratory depression, nausea/ emesis, an increase in cerebral blood flow (a decrease in cerebral metabolic demand). It can cause malignant hyperthermia, a rare, life threatening hereditary condition in which inhaled anesthetics and succinylcholine induce fever and severe muscle contraction. Treatment of dantrolene.
N2O
An inhaled anesthetic with unknown mechanism. Effects include myocardial depression, respiratory depression, nausea/ emesis, an increase in cerebral blood flow (a decrease in cerebral metabolic demand). It can cause expansion of trapped gas in a body cavity.
Thiopental
A barbiturate used as an intravenous anesthetics. High potency, high lipid solubility, rapid entry into brain.It is used for induction of anesthesia and short surgical procedures. It’s effect is terminated by it’s rapid distribution into tissue (ie skeletal muscle) and fat. It decreases cerebral blood flow.
Midazolam
A benzodiazepine used as an intravenous anesthetic. Midazolam is the most common drug used for endoscopy. It is used adjectively with gaseous anesthetics and narcotics. It may cause severe postoperative respiratory depression, decrease in BP (treat overdose with flumazenil), anterograde amnesia.
Arylcychlohexylamines
Also called ketamine, which can be used as an intravenous anesthetic. It is a PCP analog that acts as a dissociative anesthetics. It blocks NMDA receptors. Cardiovascular stimulants. Cause disorientation, hallucination, bad dreams. It increases cerebral blood flow.
Opioids used as an intravenous anesthetic
Morphine, fentanyl used with other CNS depressants during general anesthesia.
Propofol
It is an intravenous anesthetic. It is used for sedation in the ICU, rapid anesthesia induction, for short procedures. There is less postoperative nausea than thiopental. It potentiates GABAa.
Structures of local anesthetics
Esters include procaine, cocaine, tetracine. Amides include ildocaine, mepivacaine, bupivaine (amIdes have two I’s in the name).
Mechanism of local anesthetics
The majority of local anesthetics function by blocking voltage gated Na+ channels, causing a disruption of impulse transmission in pain fibers. Local anesthetics can be classified chemically as esters and amides. Esters can be remembered as having one “i,” and include procaine, cocaine, tetracaine. Amides can be remembered as having two “i’s,” and include lidocaine, mepivacaine, bupivacaine. Local anesthetics are most often used for minor surgical procedures and spinal anesthesia. If the patient is allergic to esters, amides can be administered. Local anesthetics are often co-administered with vasoconstrictors, which decreases local anesthetic absorption into the systemic circulation. This allows for prolonged effects and decreased toxicity.
Efficacy of local anesthetics
Characteristics of the nerve fibers contribute to the efficacy of local anesthetics. Size: Fibers with a smaller diameter are more easily blocked (dominant factor). Myelination: Myelinated fibers are more easily blocked than unmyelinated fibers. Order of Blockade: small myelinated> small unmyelinated> large myelinated > large unmyelinated. The fibers of different sensory modalities possess different characteristics causes loss of sensations in a specific order: Pain (lost first) > temperature > touch > pressure (lost last)
Toxicity of local anesthetics
Toxicity of local anesthetics is related to concentration levels. The most common cause of toxic levels is accidental injection into a blood vessel. The most common toxicities include: CNS excitation including tinnitus, disorientation, and seizures can occur from local anesthetics. Severe cardiovascular toxicity can occur with bupivacaine. Other cardiovascular problems seen with local anesthetics including hypertension and hypotension. Cardiac arrhythmias can result from cocaine. Methemoglobinemia can result from administration of benzocaine and prilocaine.
Neuromuscular blocking drugs
They cause muscle paralysis in surgery or mechanical ventilation. They are selective for motor (vs autonomic) nicotinic receptor. There are two types: depolarizing and nondepolarizing.
Depolarizing neuromuscular blocking drugs
Depolarizing agents achieve blockade of the NMJ by over activation of the normal agonist pathway. The only depolarizing agent currently used in the US is succinylcholine. Depolarizing agents work in 2 phases: a depolarizing phase and a desensitizing phase. In phase I block (depolarizing phase), succinylcholine binds the receptor and depolarizes the membrane, which causes an initial discharge that produces fasciculations followed by a flaccid paralysis. Because succinylcholine is metabolized slowly, the membrane becomes unresponsive to further impulses. In phase II block (desensitizing phase), the membrane eventually repolarizes, however it remains unresponsive because it is desensitized. During later phase II, desensitizing agents are susceptible to reversal by ACh esterase inhibitors.
Nondepolarizing neuromuscular blocking drugs
Non-depolarizing agents achieve blockade by physically limiting access of the agonist to the receptor (i.e. functions as a competitive antagonist). These represent the majority of NMJ blocking agents that are clinically used. Non-depolarizing agents are competitive antagonists of ACh at the nicotinic AChR (most commonly those at the NMJ). Because the non-depolarizing agents are competitive antagonists of the AChR, their effect can be reversed by acetylcholine esterase inhibitors such as neostigmine and pyridostigmine. Adverse effects of these non-depolarizing agents include weak muscarinic ACh antagonism and histamine release.
Complications of depolarizing neuromuscular blocking drugs
Complications of depolarizing neuromuscular blocking drugs include: Hypercalcemia, Hyperkalemia, Malignant hyperthermia.
d-Tubocurarine
It is a nondepolarizing neuromuscular blocking drugs. d-Tubocurarine is the prototypical non-depolarizing agent. Because of long duration of action, useful for surgical paralysis. Use has been supplanted by newer agents.
Atracurium
It is a nondepolarizing neuromuscular blocking drugs. Atracurium similar to tubocurarine in duration of activity but does not have anticholinergic effects. Because atracurium is eliminated in the liver by ester hydrolysis, it is the drug of choice in patients with renal impairment.
Rocuronium
It is a nondepolarizing neuromuscular blocking drugs. Rocuronium is useful in patients with renal impairment (hepatic excretion). Because its action of duration is 20-40 min, it is useful for short surgical procedures.
Vecuronium
It is a nondepolarizing neuromuscular blocking drugs. Vecuronium is a tubocurarine analog with intermediate duration of activity.
Mivacurium
It is a nondepolarizing neuromuscular blocking drugs. Mivacurium has a rapid onset with a short duration of activity (10-20 mins). It is metabolized in the blood stream by plasma cholinesterase.
Dantrolene
It prevents the release of Ca from sarcoplasmic reticulum of skeletal muscles. It is used to treat malignant hyperthermia and neuroleptic malignant syndrome (a toxicity of antipsychotic drugs).
Baclofen
It inhibits GABAb receptors at spinal cord level, including skeletal muscle relaxation. It is used to treat muscle spasms (eg acute low back pain).
Cyclobenzaprine
It is centrally acting skeletal muscle relaxant. It is structurally related to TCAs, similar anticholinergic side effects. It is used to treat muscle spasms.
Treatment of parkinson’s disease
use the mnemonic “BALSA”: Bromocriptine, Amantadine, Levodopa and carbidopa, Selegiline, Antimuscarinics
Dopamine agonists
It is used to treat Parkinson’s disease. Bromocriptine is a dopamine receptor agonist (ergot alkaloid). Newer non-ergot dopamine receptor agonists such as pramipexole and ropinirole are now preferred for the treatment of Parkinson disease over bromocriptine, which is associated with a less favorable side effect profile.
Drugs that increase dopamine availability
It is used to treat Parkinson’s disease. These agents prevent peripheral (pre blood brain barrier) L-dopa degradation causing an increase in L-DOPA entering the CNS, thereby increasing the amount of central L-DOPA available for conversion to dopamine. Drugs in this category include levodopa/carbidopa, entacopone and tolcapone.
Levodopa/carbidopa
Carbidopa blocks peripheral conversion of L-DOPA to dopamine by inhibiting DOPA decarbocylase. It also reduces side effects of decarboxylase. It also reduces side effects of peripheral L-DOPA conversion into dopamine (eg nausea and vomiting). Toxicities include arrhythmias from an increase in peripheral formation of catecholamines. Long-term use can lead to dyskinesia following administration (on-off phenomenon), akinesia between doses.
Entacapsone and tolcapone
It is used to treat Parkinson’s disease. It prevents peripheral L-DOPA degradation to 3- O-methlydopa (3-OMD) inhibiting COMT.
Drugs that prevent dopamine breakdown
It is used to treat Parkinson’s disease. These agents act centrally (post blood brain barrier) to block breakdown of dopamine, causing an increase in available dopamine. Selegiline blocks conversion of dopamine into 3-MT by selectively inhibiting MAO-B. Tolcapone blocks conversion of dopamine to DOPAC by inhibiting central COMT.
Benztropine
It is used to treat Parkinson’s disease. It is used to curb excess cholinergic activity. It is an antimuscarinic that improves tremor and rigidity but has little effect on bradykinesia. Park your mercedes-Benz.
Selegiline
A seletively inhibits MAO-B, which preferentially metabolizes dopamine over norepinephrine and 5-HT, thereby increasing the availability of dopamine. It is used as an adjunctive agent to L-DOPA in treatment of Parkinson disease. It may also enhance the adverse effects of L-DOPA.
Memantine
It is used to treat Alzheimer. It is an NMDA receptor antagonist. It helps prevent excitotoxicity (mediated by Ca). Toxicities include Dizziness, confusion, and hallucinations.
Donepezil
It is used to treat Alzheimer. It is an AChE inhibitor. Toxicities include nausea, dizziness, insomnia.
Galantamine
It is used to treat Alzheimer. It is an AChE inhibitor. Toxicities include nausea, dizziness, insomnia.
Rivastigmine
It is used to treat Alzheimer. It is an AChE inhibitor. Toxicities include nausea, dizziness, insomnia.
Tacrine
It is used to treat Alzheimer. It is an AChE inhibitor. Toxicities include nausea, dizziness, insomnia.
Neurotransmitter changes in Huntington disease
A decrease in GABA, a decrease in ACh, an increase in dopamine.
Tetrabenazine
It is used to treat Huntington disease. It inhibits vesicular monoamine transporter (VMAT). It limits dopamine vesicle packaging and release.
Reserpine
It is used to treat Huntington disease. It inhibits vesicular monoamine transporter (VMAT). It limits dopamine vesicle packaging and release.
Haloperidol
It is used to treat Huntington disease. It is a D2 receptor antagonist.
Sumatriptan
It is a 5-HT agonists. It inhibits trigeminal nerve activation. It prevents vasoactive peptide release. It also induces vasoconstriction. It is used to treat acute migraine and cluster headache attacks. Toxicities include coronary vasospasm (contraindicated in patients with CAD or Prinzmetal angina), and mild paresthesia. A SUMo wrestler TRIPs ANd falls on your head.
