Notes 2A Flashcards
Fencer’s posture in a seizure is assoc with and indicates activation of?
frontal lobe epilepsy and indicated activation of the supplementary motor area
Gabapentin can worsen what seizures?
Generalized, especially myoclonus
MOA of gabapentin?
Works by interacting with the alpha2-omega subunit of presynaptic L-type voltage-regulated calcium channel
Pregabalin has a higher bioavailability
Risk of patient with simple febrile seizures will develop epilepsy?
5%
Generalized epilepsy with febrile seizures + is assoc with what gene
SCN1A mutation (alpha subunit of a sodium channel)
Progressive myoclonic epilepsy are due to (2)
features
treatment?
- lysosomal or mitochondrial disorders
- cognitive decline, myoclonus (epilepstic and non epileptic), and seizures, and may be associated with ataxia or movement disorders
VPA is first line always
VPA is a P450 inducer or inhibitor?
inhibitor
Normal PDR is seen at what age?
8-10
Ranges for each frequency on EEG
Beta > 14 Hz, alpha 8 - 13 Hz, delta 4-7 Hz, omega < 4 Hz
EEG in JME
4-6 Hz polyspike and wave
Benign rolandic epilepsy (also aka benign childhood epilepsy with centrotemporal spikes): EEG findings
bilateral independent centrotemporal spikes on normal background
West Syndrome triad?
Hypsarrhythmia
Infantile Spasms
psychomotor arrest/aggression
Causes of West Syndrome? Treatment?
ischemic injuries, brain malformations, congenital or acquired infections, chromosomal abnormalities, and inborn errors of metabolism
ACTH or Vigabtrin
Lamotrigine and OCP interaction
Only OCPs with estrogen ethinylestradiol interact -> inc clearance/decreases blood concentration of LTG
Progesterone containing OCPs are gucci
MOA of lacosamide
slow inactivation of voltage gated Na channels
Rufinamide: MOA, cleared by, approved for?
Na channels: prolongs the inactive state of Na channels
renal clearance
adjunct tx for LGS
Mesial Temporal Sclerosis semiology
- Behavioral arrest, preceded by aura (rising epigastric sensation, nausea, olfactory and or gustatory hallucinations, a sensation of fear or terror, or other emotional changes)
- Autonomic manifestations: tachycardia, resp changes, face flushing, pallor…
- Dymnesic manifestations: deja vu, deja entendu, jamais vu, jamais entendu, panoramic vision (a rapid recollection of episodes in the past)
- Automatism (nose picking, lip smacking, chewing, and picking with the hands)
Aicardi Syndrome:
Inheritance
features (triad)
Boys or girls?
X linked dominant
Infantile spasms, chorioretinal lacunae and agenesis of the corpus callosum
lethal in boys, typically only girls
Doose Syndrome
Onset
features
Treatment
Myoclonic-astatic epilepsy
1-5yo
normal prior to seizure onset, then develop generalized seizures (myoclonic or atonic usually).
VPA is first line
Dravet’s Syndrome
initial pres and features
assoc with mutation of
Treatment
initially presents with a febrile seizure in first year of life that develops into partial or generalized sz and developmental delay
SCN1A
VPA, TPM, ZNS, ketogenic diet
Which drugs worsen Dravet Syndrome (4)
PB
Phenytoin
CBZ
LTG
Ohtahara Syndrome
age group
presentation
prognosis
Early infantile epileptic encephalopathy
1day-3mo
tonic spasms occurring multiple times a day with interictal EEG showing encephalopathy
poor prognosis
Benign myoclonic epilepsy of infancy
males/females
onset
features
EEG
Tx?
males
4mo-3y
brief myoclonic seizures that are easily treatable and do not cluster
Interictal EEG is normal
Treat with VPA, resolves in a year usually
Difference between Ohtahara EEG and Benign myoclonic epilepsy
Ohtahara has an ABNORMAL interictal EEG.
Benign neonatal seizures
onset
features
assoc with
treatment
day 5ish
partial tonic clonic seizures
associated with apnea spells
No need to treat, resolves by 4-6 weeks
Panayiotopoulos Syndrome
Onset
features
EEG
Tx
Early onset childhood occipital epilepsy
seizures consist of tonic eye deviation and vomiting, visual auras and occur during sleep
EEG with occipital spikes which disappear with eye opening and reappear with eye closure
No tx needed, good prog
Gastaut type childhood occipital epilepsy
same as Panayiotopoulos but later onset (8yo)
usually benign, AEDs sometimes needed
Lennox Gastaut Syndrome
Features
onset
Tx
Triad of multiple seizure types (atypical absence, tonic, atonic, myoclonic and GTC), EEG with diffuse slow 1-2Hz spike and wave complexes, cognitive delay
1-8yo (sometimes normal before seizure onset)
VPA and clonazepam are first line (can also use LTG, felbamate, TPM, vigabatrin)
Landau Kleffner Syndrome
Features
Age
Tx
acquired epileptic aphasia- aphasia assoc with epileptic patterns on EEG and seizure of various types
2-11yo
VPA or LTG
Autosomal nocturnal frontal lobe epilepsy
Features
EEG
Assoc with gene mutation?
Tx
bizarre episodic behaviors in the context of hypermotor seizures (thrashing and jerking) that occur during non-REM sleep
EEG with epileptic activity during motions and normal interictally.
Assoc with nicotinic ACH receptors (CNRNA4 and CHRNB2)
CBZ or OXC
Electrical Status Epilepticus during slow wave sleep (ESES)
Features
EEG
children with psychomotor impairment and multiple seizure types that occur more often during sleep
- EEG shows slow spikes-wave complex occurring during non-REM sleep occupying at least 85% of slow-wave sleep time
Progressive Myoclonic Epilepsies (5)
- Unverricht– Lundborg syndrome
- Lafora body disease
- MERRF
- sialidosis Type 1 and 2
- Neuronal ceroid lipofuscinosis
Unverricht-Lundborg Syndrome
inheritance
age
mutation
presentation
Tx
autosomal recessive
6-15yo
mutation in CSTB gene to make cystatin B
stimulus sensitive myoclonus, eventually progressing to focal and generalized seizures and neurologic deterioration: ataxia, tremors, cognitive decline
VPA, clonazepam, LEV, ZNS
Which ASMs make Unverricht-Lundborg seizures worse
myoclonic so phenytoin, LTG, carbamazepine, oxcarbazepine, vigabatrin, tiagabine, gabapentin, and pregabalin
MERRF (mitochondrial epilepsy with ragged red fibers)
features
mitochondrial disorder consisting of myoclonic seizures +
migraine, short stature, ataxia, cog delay, deafness, elevated lactate, proximal muscle weakness suggestive of myopathy
Salidosis Type 1
mutation
features
alpha neuraminidase deficiency
action myoclonus, slowly progressive ataxia, GTC, vision loss
fundoscopic exam with cherry red spot
Sialidosis Type 2
mutation
features
NEU1 gene on chromosome 6 (deficiency of N-acetyl neuraminidase and beta-galactosialidase)
myoclonus with coarse features, corneal clouding, hepatomegaly, skeletal dysplasia and learning disabilties.
Lafora Body Disease
inheritance
mutation
features
micro
auto rec
EPM2A on chromosome 6
generalized and focal myoclonic seizures, transient blindness and visual hallucinations
PAS+ intracellular inclusion bodies
Simple febrile seizure
generalized, usually isolated, and lasting less than 15 mins
complex febrile seizure
more than 15 mins
focal features, multiple times within 24 hour period
higher risk of subsequent epilepsy
Recurrent febrile seizures may occur if
family hx of FS
<18 mo at time of first FS
lower peak temperature and shorter duration of fever prior to first FS
Rasmussen Encephalitis: mutation
Ab against GluR3 subunit of the AMPA receptor
Risk factors that increase the chance of SJS after initiation of ASMs like CBZ, LTG
Asian decent
HLA-B 1502
Normal sleep consists of how many cycles of NREM/REM
4-6
Characteristics of sleep stage 1
attenuation of occipital predominant alpha rhythm
can see POSTs and vertex waves
Characteristics of sleep stage 2
presence of K complexes, sleep spindles
Characteristics of sleep stage 3
slow wave sleep, delta range
Characteristics of REM sleep
rapid eye movements, sawtooth waves, atonic muscles (except for diaphragm and extraocular muscles)
Amount of time in REM sleep increases or decreases with age?
DEC
What drug notoriously reduces length of REM cycles and increases REM latency?
SSRI
OSA is diagnosed based on
AHI = complete cessation or reduction of airflow for at least 10 seconds
5-15 = mild
15-30 = mod
30+ = severe
REM sleep behavior disorder is highly associated with?
alpha synucleinopathies
Parkinson, MSA, Lewy Body Dementia
Low HR in REM is a sign of
dysautonomia
NonREM parasomnias typically occur in what stage? Examples of these
Stage 3
confusional arousal, sleep walking, sleep terrors
Kleine-Levin Syndrome
Features
recurrent episodes of hypersomnia that occur weeks/months apart that last for several days to weeks.
Episodes consist of 18-20 hours of sleep a day, hyperphagia (eating a lot) and hyper-sexuality
In between episodes patients have normal sleep behavior
Narcolepsy diagnostic criteria
Excessive daytime sleepiness + any of these
- Mean sleep latency <8 min on MSLT with >2 sleep onset REM periods
- REM sleep latency < 15 mins on PSG
Narcolepsy with cataplexy (aka Narcolepsy Type 1) is characterized by? Assoc with
episodes with sudden loss of motor tone of voluntary muscles
Assoc with low CSF hypocretin
Low CSF hypocretin assoc with Narcolepsy with cataplexy comes from?
loss of hypocretin int the lateral hypothalamus
(not seen in narcolepsy without cataplexy)
Treatment for narcolepsy with cataplexy?
First line is gamma-hydroxybutyrate
others are TCAs, SSRIs
RLS is associated with a deficiency of
iron, ferritin is typically less than 50
Normal Direct movement pathway
Excitatory pathway
- striatum + GPi+ SNr+ thalamus
- Normally causes inhibition of GPi and SNr which results in less inhibition of the thalamus and increasing thalamic outflow to the cortex
Normal indirect movement pathway
Inhibitory Pathway
- Striatum + GPe + STN + GPi + thalamus
- In this pathway, striatum inhibits GPe cousing less inhibition of sub thalamus which will activate the GPi and SNi which will inhibit the thalamus
- Ultimately the indirect pathway will decrease the thalamic outflow to the cortex
Major outflow of the basal ganglia arises in the
globus pallidus interna
In PD, what happens to these BG pathways?
- the substantial nigra pars compacts projects to the striatum, inhibiting the indirect pathway and exiting the direct pathway (in the case of PD)
Hyperkinetic movement disorders result from ?
reduced activity in the indirect pathway
Hypokinetic movement disorders result from
reduced action in the direct pathway
D1 receptors are involved mainly in what pathway
direct
D2 receptors are involved mainly in what pathway
indirect
PD with dementia is a diagnosis made when
the patient meets criteria for idiopathic PD for at least 1 year before dementia onset
Mutations involved in hereditary PD?
- α-synuclein (PARK1 gene), leading to abnormalities in synaptic vesicle trafficking. Autosomal dominant, young onset.
- Parkin (PARK2 gene), a ubiquitin E3 ligase. Autosomal recessive, juvenile onset.
- Leucine-rich repeat kinase 2 (LRRK2 and PARK8 gene). The LRRK2 mutation is one of the most common causes of familial PD. Autosomal dominant
MOA of entocapone
COMT inhibitor
(inhibit conversions of dopamine to its metabolite, extending its half life and reducing “off” periods and increasing “on” periods)
MOA of carbidopa
decreases conversion of peripheral dopamine so it can cross BBB
MOA of pramipexole and ropinirole
D2/D3 agonists
MOA of rasagiline and selegiline
MAO-B inhibitors
MOA of trihexyphenidyl
Anticholinergic used only for tremors
MOA of amantadine
(antagonist of NMDA): anti-glutaminergic
SE of dopamine agonists
sedation, LE edema, impulse control problems
SE of levodopa
dyskinesias and choreiform movements, which develop the longer you take the medication and as dosages increase
DBS for PD is effective in reducing what symptoms, and ineffective in what else?
reducing tremor and bradykinesia
but not in improving gait, falls, or axial sx
Contraindications to DBS for PD?
cognitive dysfunction, can worsen it significantly
nuclei targeted in DBS for PD?
subthalamic nucleus and globus pallidus interna
What nuclei can be targeted with DBS in PD for tremor dominant PD?
ventral intermediate nucleus
Potential fatal feature that can occur in MSA is?
laryngeal dystonia
Hot cross buns sign is seen in? Due to?
MSA
neuronal loss in the pons and pontocerebellar tracts with intact corticospinal tracts
Features of corticobasal syndrome
focal limb rigidity and/or dystonia, cortical myoclonus, cortical sensory loss, alien limb
Unilateral lesion in the substantia nigra will cause?
contralateral hemiparkinsonism
Toxicities that can cause parkinsonism?
Manganese and CO
Manganese toxicity
population
features
imaging
seen in welders/miners, patients with chronic liver disease, and on TPN.
parkinsonism, typical gait cock walk (toe walking with elbow flexion)
hyperintense BG on T1
Essential tremor
inheritance
Tx options
Resistant tx
AD
propranolol, primidone are main. Then you have gabapentin, atenolol, topiramate, benzos
If resistant → DBS to the ventral intermediate nucleus of thalamus
Huntingtons Disease
mutation
Tx
CAG repeat
antidopaminergics like tetrabenazine and atypical antipsychotics
Rubral tremor
features
caused by
aka Holmes tremor
low frequency tremor present at rest, with posture and with action
lesion in the dentate nucleus of the cerebellum, or superior cerebellar peduncle
Tourette’s Syndrome
assoc with
possible MOA
tx
ADHD and OCD
thought to involve dopaminergic hyper stimulation of the ventral striatum and limbic system
Tx with antidopaminergic agents like haloperidol, pimozide, clonidine
Wilson’s Disease
mutation
labs
features
MRI findings
tx
- Mutation of gene encoding the copper transporting P type ATPase ATP7N on Xome 13 ( the enzyme usually transports copper across membranes)
- low ceruloplasmin, high urine copper
- parkinsonism, dystonia, tremor, ataxia, dysarthria
- Double panda sign: inc T2 signal in caudate and putamen while sparing red nucleus
- tx with D-penicillamine , zinc and low copper diet
Sydenham chorea
typically after
treat with
GBS infection
antidopaminergics
Chorea acanthocytosis
mutation
features
wet smear shows
VPS13A on chromosome 9
- orolingual dystonia, chorea, self mutilating behavior, cognitive decline with dementia, dysarthria, ophthalmoplagia, seizures
acanthocytes (speculated RBCs on wet smear)
trick to relieve sx of focal dystonia? main treatment of dystonia
gest antagoniste
- a sensory trick (geste antagoniste) such as touching the face or head or positioning the head in a specific manner against an object, may partially relieve Sx
- Main tx is botox
Meige’s Syndrome
blepharospasm + oromandibular dystonia
Tolosa Hunt Syndrome
what is it
features
tx
Inflammation of cavernous sinus
- episodic orbital pain associated with paralysis of one or more of the third, fourth, and/or sixth cranial nerves, which usually resolves spontaneously
- responds to steroids
Palatal myoclonus
what is it
- Audible palatal clicks due to Eustachian tube contraction
- Persist during sleep
- Affects the Guillain-Malloret triangle (dentate nucleus, inferior olive and the red nucleus)
Hemifacial spasm can be caused by?
compression of CN 7, or sometimes demyelination of CN7.
Blink reflex is also usually affected.
Paroxysmal kinesigenic dyskinesia (PKD)
features
tx
episodes of hyperkinetic abnormal movements for seconds to about 5 mins (dystonia, chorea, ballism, dysarthria) with intervening normalcy
responds well to ASMs, usually CBZ
Paroxysmal nonkinesigenic dyskinesia
features
attacks last 2mins - hours
do not respond well to tx
Paroxysmal exertion dyskinesia (PED)
features
mut
tx
episodes of hyperkinetic abnormal movement assoc with exercise and last 5-30min
mutation in GLUT-1
keto diet can decrease frequency
Features of dopa-responsive dystonias
diurnal variation
sx more severe at end of day and improved in the morning. Sx also commonly start at the feet and become generalized
strongly responsive to levodopa
Stiff person syndrome
features
antibody
tx
- Characterized by increased tone affecting predominantly the axial muscles, including the paraspinal muscles, leading to exaggerated lumbar lordosis, in addition to abdominal muscles, leading to a “board-like” abdomen, exaggerated startle response.
- assoc with GAD ab
- tx with benzos or baclofen
Paraneoplastic type of stiff person syndrome is assoc with
antiamphiphysin
Main output cell of the cerebellum? inhibitory/excitatory? NT?
purkinje
inhib
GABA
alcohol predominantly affects what part of the cerebellum and thus causes?
midline vermis
truncal ataxia
Freidrich’s ataxia
inheritance, mutation
features
AR
GAA repeat in gene that encodes frataxin on chromosome 9
cerebellar dysfunction, neuropathy, upper motor neuron findings, high-arched feet and spinal deformities, Cardiac involvement (conduction abnormalities and hypertrophic cardiomyopathy)
What med can improve the HCM seen in Friedrich’s ataxia
Idebenone, a Coenzyme q10 analog
Which medications can worsen absence seizures?
Phenytoin, gabapentin, carbamazepine, and LTG
Formula for replacing phenytoin/VPA?
(target level (15) - current level) X (weight in KG x volume of distribution(usually 0.8))
For example in someone who is 75kg and level of 10, would need 300mg load.
Depakote is same formula except volume of distribution is 0.2
Name the CYP inducers?
CBZ
PB
PHY
OXC
vigabatrin
which receptor do benzos act on?
GABA-A receptors
MOA of lacosamide (more specific)
enhances slow inactivation of voltage dependent sodium channels, resulting in inhibition of neural firing and stabilization of hyperexcitable neuronal membranes.
**It is also known to interfere with CRMP-2 (collapsing response mediator transporter-2), a cell protein involved in neuronal differentiation and axonal guidance.
gelastic seizures originate where?
hypothalamus
