Neurology

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SIEZURES
• risk factors associated with recurrent seizures include the following:
(1) an abnormalneurologic examination,
(2) seizures presenting as status epilepticus,
(3) postictal Todd’s paralysis,
(4) a strong family history of seizures,
(5) an abnormal EEG.
• Asian individuals carrying the human leukocyte antigen allele, HLA-
B*1502, are at particularly high risk of developing serious skin
reaceactions from carbamazepine and phenytoin.

• Lamotrigine must be started at lower initial doses when used as add-on

therapy with valproic acid, because valproic acid inhibits lamotrigine
metabolism and results in a substantially prolonged half-life.

• Levetiracetam - no known drug-drug interactions-useful in the elderly

and patients on other medications.

• Topiramate can be used for both focal and generalized seizures

• barbiturates frequently cause sedation in adults, hyperactivity in
children, and other more subtle cognitive changes

• carbamazepine, oxcarbazepine, and phenytoin can worsen certain types

of generalized seizures, including absence, myoclonic, tonic, and atonic
seizures

• Lamotrigine appears to be particularly effective in epilepsy syndromes

with mixed, generalized seizure types such as JME and Lennox-Gastaut
syndrome

• Subsequent increases of AEDs should be made only after achieving a

steady state with the previous dose (i.e., after an interval of five or more
half-lives)
• Consideration for withdrawal of AED
• (1)complete medical control of seizures for 1–5 years;(start withdrawal
after 2 years
• (2) single seizure type, either focal or generalized;
• (3) normal neurologic examination, including intelligence; and
• (4) normal EEG.

• Most recurrences occur in the first 3 months after discontinuing therapy

• The most common surgical procedure for patients with temporal lobe
epilepsy involves resection of the anteromedial temporal lobe or
(amygdalohippocampectomy).
• corpus callosotomy has been shown to be effective for disabling tonic or
atonic seizures, usually when they are part of a mixed-seizure syndrome
(e.g., Lennox-Gastaut syndrome)

• Vagus nerve stimulation - referactory seizures

• Responsive NeuroStimulation
• stereotactic radiosurgery,
• laser thermoablation, and
• deep brain stimulation (DBS) other options for surgical treatment of
refractory epilepsy.
• if the patient stops having overt seizures, yet remains comatose, an EEG
should be performed to rule out ongoing status epilepticus.

• Depression occurs in ~20% of patients in epilepsy pts – SSRI

• “interictal personality.”

• sudden unexpected death in epilepsy (SUDEP), which usually affects young

people with convulsive seizures and tends to occur at night - brainstem-
mediated effects of seizures on pulmonary, cardiac, and arousal functions.

• Seizure frequency during pregnancy will remain unchanged in ~50% of

women, increase in 30%, and decrease in 20%.
• fetal abnormalities in children born to mothers with epilepsy is 5–6% -
most common malformations were defects in the cardiovascular and
musculoskeletal system

• other than topiramate, the newer antiepileptic drugs are far safer than
valproic acid.

• Monotherapy, lowest effective dose, folate (1–4 mg/d), especially during the
first trimester, oral vitamin K (20 mg/d, phylloquinone) in the last 2 weeks of
pregnancy, and the infant should receive intramuscular vitamin K (1 mg) at
birth.
AEDs
• Qt prolongation - esogabine , rufinamide
• PR prolongation – lacosamide
• Levels increased by CYP2C19 inhibitors – clobazam
• Renal stones – topiramate
• Stevens-Johnson syndrome – lamotrigine
 CVA
• Stroke is the second leading cause of death worldwide

• The definition of TIA requires that all neurologic signs and symptoms resolve
within 24 h without evidence of brain infarction on brain imaging

• A decrease in cerebral blood flow to zero causes death of brain tissue within 4–
10 min; values <16–18 mL/100 g tissue per minute cause infarction within an
hour; and values <20 mL/100 g tissue per minute cause ischemia without
infarction unless prolonged for several hours or days

• The ischaemic penumbra can be imaged by perfusion-diffusion imaging using

MRI or CT - saving the ischemic penumbra is the goal of revascularization
therapies.
• Focal cerebral infarction occurs via two distinct pathways
- necrotic pathway
- apoptotic pathway – ischaemic penumbra

• β1-adrenergic blocker (such as esmolol) can be a first step to decrease BP

≤185/110

• CEREBRAL Edema peaks on the second or third day but can cause mass
effect for ~10 days. hemicraniectomy markedly reduces mortality

• NINDS study used IV rtPA (0.9 mg/kg to a 90-mg maximum; 10% as a bolus,
then the remainder over 60 min WITHIN 3hrs
• Symptomatic intracranial hemorrhage occurred in 6.4%
• (ECASS) III explored the safety and efficacy of rtPA in the 3- to 4.5-h time window
• The Prolyse in Acute Cerebral Thromboembolism (PROACT) II trial found benefit
for intraarterial prourokinase in acute MCA occlusions up to the sixth hour
following on set of stroke.
• Intraarterial administration of a thrombolytic agent for acute ischemic stroke (AIS)
is not approved by the U.S. Food and Drug Administration (FDA)
• SYNTHESIS trial- IV rtPA versus intraarterial rtPA for patients within 3 h of stroke
onset. No differences were found between the groups at 90 days.

• (MERCI) and multi-MERCI single-arm trials found that an endovascular

thrombectomy device restored patency of occluded intracranial vessels within 8 h
of ischemic stroke symptoms compared with a historical control group
• FDA approved this device as the first device for revascularization of occluded
vessels in AIS
• International Stroke Trial (IST) and the Chinese Acute Stroke Trial (CAST)-
found that the use of aspirin within 48 h of stroke onset reduced both
stroke recurrence risk and mortality minimally.

• TOAST trial – LMWH

• Neuroprotectives - multiple human trials, they have not yet been proven to
be beneficial.
• Hypothermia is a powerful neuroprotective treatment in patients with
cardiac arrest

• brain imaging, blood glucose, and perhaps PTT/international normalized

ratio (INR) are necessary prior to IV rtPA
• Cardioembolism is responsible for ~20% of all ischemic strokes.