NMJ disorders, sleep, mitochondrial encephalopathies Flashcards
Spinal muscular atrophy on EMG will present as _
Spinal muscular atrophy on EMG will present as fibrillation potentials, denervation, and increased amplitude of motor unit potentials
Fatiguing ptosis, double vision, dysarthria, dysphagia, and general weakness after muscle use is classic for [NMJ disorder]
Fatiguing ptosis, double vision, dysarthria, dysphagia, and general weakness after muscle use is classic for myasthenia gravis
Classic signs for lambert-eaton syndrome include _
Classic signs for lambert-eaton syndrome include slowly progressive leg weakness, constipation, dry mouth
* Sometimes see ptosis and diplopia
Botulism involves rapid [direction] paralysis with respiratory failure, constipation, and mydriasis
Botulism involves rapid descending paralysis with respiratory failure, constipation, and mydriasis
* Ocular, bulbar, extremities
Ascending paralysis with areflexia and sensory loss is suggestive of _
Ascending paralysis with areflexia and sensory loss is suggestive of guillain-barre
Botulism affects the [proteins]
Botulism affects the SNARE proteins
* Decreases release of Ach
Myasthenia gravis exerts its effects via [mechanism]
Myasthenia gravis exerts its effects via antibodies to the post-synaptic Ach receptors
Lambert-eaton myasthenic syndrome exerts its effect via [mechanism]
Lambert-eaton myasthenic syndrome exerts its effect via antibodies against voltage-gated Ca2+ on presynaptic membrane
(MG/LES) is associated with reduced Ach release
LES is associated with reduced Ach release
(MG/LES) symptoms can transiently improve after brief activation
LES symptoms can transiently improve after brief activation
Edrophonium and ice pack tests can be used for the diagnosis of _ (will cause improvement of symptoms)
Edrophonium and ice pack tests can be used for the diagnosis of myasthenia gravis (will cause improvement of symptoms)
MG is associated with underlying [condition]
MG is associated with underlying thymoma
LES is associated with underlying [condition]
LES is associated with underlying small cell lung carcinoma
Three anticholinesterase drugs that cross the BBB and can be used for Alzheimer disease:
Three anticholinesterase drugs that cross the BBB and can be used for Alzheimer disease: Dona Riva dances at the gala
1. Donepezil
2. Rivastigmine
3. Galantamine
_ is an anticholinesterase drug that we historically used to diagnose MG
Edrophoniumis an anticholinesterase drug that we historically used to diagnose MG
* Has since been replaced by anti-AchR antibody testing
_ is a long acting anticholinesterase that is used to treat MG; though it is a bandaid treatment
Pyridostigmine is a long acting anticholinesterase that is used to treat MG; though it is a bandaid treatment
* Increases Ach –> improves muscle strength
* Does not cross the BBB
MG on EMG will show _
MG on EMG will show amplitude decrement on repetitive nerve stimulation
_ and _ are two antibiotic classes that should be avoided in patients with MG
Aminoglycosides and Fluoroquinolones are two antibiotic classes that should be avoided in patients with MG
* Magnesium and beta blockers should also be avoided
Muscle weakness in LES tends to be in [location] > [location] and symmetric
Muscle weakness in LES tends to be in legs > arms and symmetric
* Will see areflexia or hyporeflexia
Botulism in adults involves the ingestion of _ ; while in babies it is caused by ingestion of _
Botulism in adults involves the ingestion of pre-formed toxin ; while in babies it is caused by ingestion of spores
* Treat with immunoglobulin (infant) or anti-toxin (adult)
Botulism affects [NT] release
Botulism affects Ach release
_ waves (1-3 Hz) are seen in stage N3
Delta waves (1-3 Hz) are seen in stage N3
_ waves (4-7) are seen in stage N1
Theta waves (4-7) are seen in stage N1
* Mild slowing, meditation
_ waves (8-13 Hz) are normal background waves
Alpha waves (8-13 Hz) are normal background waves
_ waves (> 13 Hz) are present during conscious thought, logical thinking, benzo use
Beta waves (> 13 Hz) are present during conscious thought, logical thinking, benzo use
* Awake and alert
Stage N1 is associated with _ waves
Stage N1 is associated with theta waves
* This is light sleep, easy to wake
Stage N2 is associated with _ waves
Stage N2 is associated with sleep spindles and K complexes
* This is the largest percentage of sleep
* Bruxism (twooth-grinding)
Stage N3 is associated with _ waves
Stage N3 is associated with delta waves
* Most prominent in first-half of night
* This is the deepest non-REM sleep
Sleepwalking, night terrors, and bedwetting are all associated with [sleep stage]
Sleepwalking, night terrors, and bedwetting are all associated with stage N3
* Can also see confusional arousals during N3
Bruxism is associated with [sleep stage]
Bruxism is associated with stage N2
REM stands for _
REM stands for rapid eye movement sleep
Dreaming, nightmares, and penile/clitoral tumescence occur during [sleep stage]
Dreaming, nightmares, and penile/clitoral tumescence occur during REM sleep
REM sleep occurs approximately every 90 minutes, with increased duration [when?]
REM sleep occurs approximately every 90 minutes, with increased duration as night progresses (longer REM towards the morning)
REM sleep involves [brain waves]
REM sleep involves beta waves
* Memory processing occurs
* Loss of motor tone
* Increased brain O2 use
* Variable pulse/BP
* Extraocular movements (PPRF)
As we age, we have _ N3 and REM
As we age, we have decreased N3 and REM
_ is the region in the hypothalamus that receives retinal inputs and serves to regulate circadian rhythms based on external light cycles
Suprachiasmatic pathway (SCN) is the region in the hypothalamus that receives retinal inputs and serves to regulate circadian rhythms based on external light cycles
The _ pathway is important for pupillary light reflex and accommodation
The pretectal pathway is important for pupillary light reflex and accommodation
Tectal (superior colliculus) pathway is needed for _
Tectal (superior colliculus) pathway is needed for reflexive head and eye movement
[NT] is particularly involved in movement, learning, memory, arousal, sleep
Ach is particularly involved in movement, learning, memory, arousal, sleep
[NT] is involved in reward, pleasure, planning, cognition, movement
Dopamine is involved in reward, pleasure, planning, cognition, movement
[NT] is important for mood, appetite, arousal, sleep-wake cycles, descending pain modulation
Serotonin is important for mood, appetite, arousal, sleep-wake cycles, descending pain modulation
[NT] is implicated in attention and arousal and is made in locus coeruleus
NE is implicated in attention and arousal and is made in locus coeruleus
The nigrostriatal pathway goes from _ to _
The nigrostriatal pathway goes from substantia nigra to striatum
The mesolimbic system includes _ to _
The mesolimbic system includes ventral tegmental area to nucleus accumbens & limbic system
The mesocortical pathway extends from _ to _
The mesocortical pathway extends from VTA to cortex
The SCN receives direct input from the _ and releases [NT] in response
The SCN receives direct input from the retina and releases NE in response –> tells pineal gland to secrete melatonin
* The SCN also controls the secretion of melatonin
The majority of slow wave sleep occurs in the _ of night while the majority of REM sleep occurs in the _
The majority of slow wave sleep occurs in the first part of night while the majority of REM sleep occurs in the second half
Normal sleep begins in _ , those with narcolepsy enter sleep directly into _
Normal sleep begins in N1-> N2 -> N3/4 -> REM , those with narcolepsy enter sleep directly into REM
Advanced sleep phase disorder involves _
Advanced sleep phase disorder involves early evening sleepiness and early morning awakening
_ sleep-phase disorder is common in adolescents and teenagers
Delayed sleep-phase disorder is common in adolescents and teenagers
Insomnia is defined as _
Insomnia is defined as difficulty getting to sleep or staying asleep or having non-refreshing sleep for at least 1 month (acute) or 3 months (chronic)
Obstructive sleep apnea is produced by _ and risk factors include _
Obstructive sleep apnea is produced by obstruction of upper airway and risk factors include age, obesity, alcohol, supine sleep
Narcolepsy is caused by an absence or reduction of _ , brain chemicals that help sustain alertness and prevent REM sleep
Narcolepsy is caused by an absence or reduction of orexin (hypocretin), brain chemicals that help sustain alertness and prevent REM sleep
Narcolepsy is associated with [HLA marker]
Narcolepsy is associated with HLA-DQB1 0602
Name the four main features of narcolepsy
Name the four main features of narcolepsy:
1. Excessive sleepiness
2. Cataplexy
3. Sleep paralysis
4. Hypnic hallucinations
Type I narcolepsy involves _ , which is a condition by which emotion causes sudden muscle weakness
Type I narcolepsy involves cataplexy , which is a condition by which emotion triggers sudden muscle weakness
Hypnagogic hallucinations (narcoplepsy) occur [when?]
Hypnagogic hallucinations (narcoplepsy) occur at onset of sleep
Hypnopompic hallucinations (narcolepsy) occur [when?]
Hypnopompic hallucinations (narcolepsy) occur at end of sleep, while waking up
_ is a condition involving a crawling sensation or urge to move the legs during rest
Restless leg syndrome is a condition involving a crawling sensation or urge to move the legs during rest
Check [lab value] in patients with restless leg syndrome
Check ferritin & iron saturation in patients with restless leg syndrome
* Often associated with iron deficiency
* Replace iron
* Or treat w gaba, pregabalin, ropinirole
REM sleep behavior disorder is associated with _ proteinopathies
REM sleep behavior disorder is associated with alpha-synuclein proteinopathies
* Lewy body dementia
* Parkinson disease
* It involves loss of normal muscle atonia during REM –> acting out dreams
Benzos are helpful for the treatment of sleepwalking and night terrors because they _
Benzos are helpful for the treatment of sleepwalking and night terrors because they decrease N3 and REM sleep
Nonbenzodiazepine hypnotic drugs include _
Nonbenzodiazepine hypnotic drugs include:
* Zolpidem
* Zaleplon
* Eszopiclone
These work by BZ1 GABA receptor
[Hypnotic drug] is a melatonin receptor agonist
Ramelteon is a melatonin receptor agonist (MT1-2 receptor)
Suvorexant is a hypnotic drug that induces sleep by [mechanism]
Suvorexant is a hypnotic drug that induces sleep by antagonizing orexin receptors
Benzos are drugs that facilitate GABAa action by _
Benzos are drugs that facilitate GABAa action by increasing frequency of Cl- channel opening
* “Frenzodiazepines”
The short acting benzos can be remembered with the mneumonic _
The short acting benzos can be remembered with the mneumonic ATOM
* Alprazolam
* Triazolam
* Oxazepam
* Midazolam
The others have active metabolites and long half life
Barbituates faciliate GABAa action by _
Barbituates faciliate GABAa action by increasing duration of Cl- channel opening
Recall the many reactions that take place in the inner membrane/matrix of the mitochondria:
Recall the many reactions that take place in the inner membrane/matrix of the mitochondria:
* TCA cycle
* Acetyl-CoA production
* Ketogenesis
* Fatty acid oxidation
Therefor metabolites are kept away from the rest of the cell
Recall that the ETC takes place in the _
Recall that the ETC takes place in the inner membrane of mitochondria
* Isolates metabolic processes in the cell
* This limits the exposures of toxic substances to the rest of the cell
Unlike the nuclear genome, the mitochondrial genome is [shape], [size], and replication is _
Unlike the nuclear genome, the mitochondrial genome is circular, small, and replication is asynchronous to mitochondrial fission and mitosis
* Recall that mitochondrial DNA only comes from mom
Mitochondrial DNA will have far more mutations than nuclear DNA due to _
Mitochondrial DNA will have far more mutations than nuclear DNA due to less proofreading, faulty polymerase, exposure to ROS
_ is when a variant exists on some, but not all copies of the mitochondrial genome
Heteroplasmy is when a variant exists on some, but not all copies of the mitochondrial genome
* As opposed to homoplasmy
* We use these terms instead of homo/heterozygous because mitochondria are not diploid
The fact that a certain amount of heteroplasmy may be tolerated without clinical effect is called _ ; heteroplasmy can change over time and external factors can change the threshold (especially metabolic stress)
The fact that a certain amount of heteroplasmy may be tolerated without clinical effect is called Threshold effect
* Heteroplasmy can change over time and external factors can change the threshold (especially metabolic stress)
Mitochondrial disorders are typically progressive, triggered by _ , and affect tissues with high energy requirement like _
Mitochondrial disorders are typically progressive, triggered by metabolic stress , and affect tissues with high energy requirement like skeletal/cardiac muscle, nerves, liver, kidney, GI, endocrine glands
Mitochondrial disorders may have [non-specific lab finding]
Mitochondrial disorders may have elevated lactate/ pyruvate
Leigh syndrome is also called _ ; it is characterized by developmental delay or regression, hypotonia, dysphagia, bilateral spongiform lesions in the brain
Leigh syndrome is also called subacute necrotizing encephalomyopathy ; it is characterized by developmental delay or regression, hypotonia, dysphagia, bilateral spongiform lesions in the brain
* It exhibits locus heterogeneity
MELAS stands for _
MELAS stands for Myopathy, Encephalopathy, Lactic acidosis, Stroke-like episodes
* The mechanism is unclear but usually presents in childhood with stroke-like signs (hemiplegia, hemianopsia)
* MRS can show elevated lactate
MERRF stands for _
MERRF stands for Myoclonic Epilepsy with Ragged Red Fibers
* The ragged red fibers are abnormal mitochondrial aggregates below plasma membrane of muscle fibers
The first symptom of MERRF is usually _ followed by:
The first symptom of MERRF is usually myoclonus + cerebellar ataxia followed by:
* Epilepsy
* Myopathy and exercise intolerance
* Hearing loss
* Dementia
* Optic atrophy
Consciousness requires both awareness via a normal “hard drive” _ , and arousal via a functional on switch _
Consciousness requires both awareness via a normal “hard drive” one functioning cerebral hemisphere , and arousal via a functional on switch reticular activating system
“Unarousable unresponsiveness” defines _
“Unarousable unresponsiveness” defines coma
* Could be a lesion that destroys large area of cortex or RAS in brainstem
Persistent vegetative state describes a patient who is _
Persistent vegetative state describes a patient who is arousable (eyes open) but impaired responsiveness/awareness
Minimally conscious state defines a patient who is _
Minimally conscious state defines a patient who is intact arousal with minimal reponsiveness/awareness
_ occurs from a lesion affecting the ventral pons or caudal midbrain that causes quadriplegia, bulbar palsy, and impaired horizontal gaze
Locked-in syndrome occurs from a lesion affecting the ventral pons or caudal midbrain that causes quadriplegia, bulbar palsy, and impaired horizontal gaze
* The RAS lies dorsal so it is spared
* Consciousness, vertical eye movement, blinking, hearing are preserved
Locked-in syndrome is commonly caused by thrombosis of the _ artery
Locked-in syndrome is commonly caused by thrombosis of the basilar artery
Oculocephalic reflex requires [2 CNs]
Oculocephalic reflex requires CN III, VI
* Dolls eye reflex
Nerve V1 is involved in _ reflex
Nerve V1 is involved in corneal reflex
Touching the eye for corneal reflex requires [CN] to sense, and [CN] for blink
Touching the eye for corneal reflex requires CN V to sense, and CN VII for blink
Loss of the (motor) corneal reflex suggests _ nerve palsy
Loss of the (motor) corneal reflex suggests facial nerve palsy
Loss of gag reflex may indicate lesion of [CN] or [CN]
Loss of gag reflex may indicate lesion of glassopharyngeal or vagus nerve
Gag reflex involves [CN] to sense and [CN] to trigger gag
Gag reflex involves CN IX to sense and CN X to trigger gag
In the pupillary reflex test, [CN] senses light, [CN] constricts the pupil
In the pupillary reflex test, CN II senses light, CN III constricts the pupil
Lacrimation requires [afferent CN] and [efferent CN]
Lacrimation requires V1 and VII
Cold calorics involves [CNs]
Cold calorics involves CN VIII, III, VI
Jaw jerk involves [afferent CN] and [efferent CN]
Jaw jerk involves V3 sensory and V3 motor
[Extrapyramidal tract] is responsible for upper extremity flexor tone
Rubrospinal tract is responsible for upper extremity flexor tone
* Red nucleus –> spinal cord
* Recall the red nucleus is in rostral midbrain
[Extrapyramidal tract] is responsible for upper extremity extensor tone
Vestibulospinal tract is responsible for upper extremity extensor tone
* Vestibular nuclei –> spinal cord
_ posturing happens when flexors > extensors
Decorticate posturing happens when flexors > extensors
* “Flex the core”
_ posturing occurs when extensors > flexors
Decerebrate posturing occurs when extensors > flexors
A lesion between the red nucleus and vestibulospinal tracts would result in _ posturing
A lesion between the red nucleus and vestibulospinal tracts would result in decerebrate posturing
* If you knock out the flexors, you see unopposed extension
* Extension of both arms and legs
ID the red nucleus
The vestibulo-ocular reflex works to stablize a visual image on the retina by _
The vestibulo-ocular reflex works to stablize a visual image on the retina by moving the eyes in the opposite direction of head movement
The flocculonodular lobe sends information to the vestibular nuclei through the _ peduncle
The flocculonodular lobe sends information to the vestibular nuclei through the inferior peduncle
Cold water in the ear mimics head movements _ irrigated ear
Cold water in the ear mimics head movements away from irrigated ear
* Slow eye movement will go towards the water, fast eye movement away in patient with functional vestibular system
In a patient with a normal vestibular system, cold water causes _ quick phase/ nystagmus and warm water causes _ quick phase/ nystagmus
In a patient with a normal vestibular system, cold water causes opposite quick phase/ nystagmus and warm water causes same quick phase/ nystagmus
* COWS= cold, opposite; warm, same
Therapeutic hyperventilation causes vaso (constriction/dilation)
Therapeutic hyperventilation causes vasoconstriction
* Decreased PCO2 –> vasoconstriction –> lowers cerebral blood flow
Tight autoregulation of cerebral perfusion is primarily driven by _ levels
Tight autoregulation of cerebral perfusion is primarily driven by PCO2 levels
Acute hypoxia/ energy failure of the brain –> _ –> cell necrosis & lysis
Acute hypoxia/ energy failure of the brain –> intracellular Na+ and Ca2+ accumulation –> osmotic swelling –> cell necrosis & lysis
* Also see release of glutamate and free radicals which are cytotoxic
The most vulnerable areas of the brain to hypoxia are _
The most vulnerable areas of the brain to hypoxia are areas with high metabolic demand & high concentration of excitatory neurotransmitter receptors
The very first area of brain injury during ischemia is _
The very first area of brain injury during ischemia is pyramidal neurons of hippocampus
In addition to the hippocampus, other areas of early ischemic injury are:
In addition to the hippocampus, other areas of early ischemic injury are:
* Pyramidal neurons of cortex
* Basal ganglia
* Purkinje cells of cerebellum
Irreversible neuronal injury begins after _ minutes of hypoxia
Irreversible neuronal injury begins after 5 minutes of hypoxia
The most vulnerable areas to hypoxia can be remembered by mneumonic:
The most vulnerable areas to hypoxia can be remembered by mneumonic: vulnerable hippos need pure water
* Hippocampus
* Neocortex
* Purkinje of cerebellum
* Watershed areas
In the first 12-24 hours after ischemic event the brain will show [histological features]
In the first 12-24 hours after ischemic event the brain will show eosinophilic cytoplasm + pyknotic nuclei (red neurons)
In the first 24-72 hours after ischemic event the brain will show [histological features]
In the first 24-72 hours after ischemic event the brain will show necrosis + neutrophil infiltration
In the first 3-5 days after ischemic event the brain will show [histological features]
In the first 3-5 days after ischemic event the brain will show neuronophagia + macrophages (anoxic neuron surrounded by microglial cells)
In the first 1-2 weeks after ischemic event the brain will show [histological features]
In the first 1-2 weeks after ischemic event the brain will show reactive gliosis + vascular proliferation (gliosis = astrocytes)
> 2 weeks after ischemic event the brain will show [histological features]
> 2 weeks after ischemic event the brain will show glial scar formation
* Glial scar is astrocytic processes, liquefactive necrosis, release of lysosomal enzymes
About 1 week-1 month post ischemic event, the brain will undergo some _ necrosis
About 1 week-1 month post ischemic event, the brain will undergo some liquefactive necrosis
Lesion above the red nucleus will result in _ posturing
Lesion above the red nucleus will result in decorticate posturing
* The rubrospinal and vestibulospinal will both be overactive
* Will see arm flexion, leg extension
