Pocket Medicine: The Massachusetts General Hospital Handbook of Internal Medicine (117 page)

• Treat any underlying causes, including CNS infections, intoxication, withdrawal,
etc.

• Antiepileptic drug (AED) therapy is usually reserved for Pts w/ underlying structural abnormality or an idiopathic seizure
plus
(i) status epilepticus on presentation, (ii) focal neurologic exam, (iii) postictal Todd’s paralysis or (iv) abnormal EEG

• After 1st unprovoked sz, if EEG and MRI nl → 65% sz-free at 5 y (
Lancet Neurol
2006;5:317) • For Pts w/ infrequent seizures, early (vs. delayed) intervention w/ AED ↑ time to seizure recurrence, but has no effect on long-term seizure-free status (
Lancet
2005;365:2007) • AED choice dependent on type of seizure, side effects, cost, mechanism of elimination (if hepatic or renal insufficiency), teratogenesis and drug interactions • Introduce gradually, monitor carefully • May consider withdrawal if seizure-free (typically for at least 1 y) and normal EEG

• Individual state laws mandate seizure-free duration before being allowed to drive

Status epilepticus (consult neurology)

• Place Pt in semiprone position to ↓ risk of aspiration • Oral airway or, if prolonged, endotracheal intubation • IV access, start normal saline infusion • STAT labs including glc, Na, Ca, serum & urine toxicology screen, anticonvulsant levels • Thiamine (100 mg IV)
prior to d
extrose to prevent Wernicke’s encephalopathy • Dextrose (50 g IV push)

ALCOHOL WITHDRAWAL

Pathophysiology

• Alcohol is a CNS depressant • Chronic use → insensitivity to inhibitory neurotransmitter g-aminobutyric acid (GABA) • Abrupt alcohol cessation → CNS overactivity
Clinical manifestations

• Minor withdrawal sx (6–48 h after last drink): mild anxiety, tremulousness, HA •
Withdrawal seizures
: typically w/in 48 h after last drink; if unRx’d,
¹
⁄
₃
→ delirium tremens •
Alcoholic hallucinosis
: isolated hallucinations (typically visual) 12–48 h after last drink •
Delirium tremens
(
DT
): disorientation, agitation, hallucinations, ↑ HR & BP, fever, diaphoresis; begins 48–96 h after last drink, lasts 5–7 d • Consider other dx: CNS infxn or bleed, sz, drug O/D, coingestions, acute liver failure, GIB

Clinical Institute Withdrawal Assessment scale for alcohol (CIWA-Ar)

• Assign points for each of the 10 criteria; each criteria is scored 0–7 except orientation which is scored 0–4; add points to calculate score

Treatment (
NEJM
2003;348:1786)

•
Benzodiazepines
(BDZ)

Drug: diazepam (long-acting w/ active metab; ↓ risk of recurrent withdrawal), lorazepam (short half-life), chlordiazepoxide, oxazepam (no active metab; good if cirrhosis)

Route: start IV, transition to PO

Dosing: typically start w/ diazepam 10–15 mg IV q10–15min (or lorazepam 2–4 mg IV q15–20min) until appropriate sedation achieved, then titrate to CIWA-Ar scale, evaluating q1h until score <8 × 8 h, then q2h × 8 h, and if stable, then q4h (
JAMA
1994;272:519)

• If refractory to BDZ prn, consider BDZ gtt, phenobarbital or propofol (& intubation) •
Avoid
haloperidol (↓ seizure threshold) or βB/central ɑ
₂
-agonists (mask sx) • Mechanical restraints as needed until chemical sedation achieved • Volume resuscitation as needed; thiamine
then
glc to prevent
Wernicke’s encephalopathy
(ataxia, ophthalmoplegia, short-term memory loss); replete K, Mg, PO
₄

• Prophylaxis: if min sx or asx (ie, CIWA score <8) but prolonged heavy EtOH con-sumption or h/o withdrawal seizures or DTs → chlordiazepoxide 25–100 mg (based on severity of EtOH use) q6h × 24 h, then 25–50 mg q6h × 2 d

STROKE

ISCHEMIC STROKE

Etiologies

• Embolic (~75%): artery → artery, cardioembolic, paradoxical (
NEJM
2007;357:2262), cryptogenic • Thrombotic (~25%): large vessel (atherosclerosis) vs. small vessel (“lacunar,” lipohyalinosis of small arteries, often related to HTN, hyperlipidemia, & DM) • Other: dissection, vasculitis, vasospasm, prothrombotic states, hypoperfusion, genetic
Clinical Manifestations

• Timing: embolic → sudden onset; thrombotic → stuttering course

Transient ischemic attack (TIA)

• Sudden deficit due to cerebral ischemia;
no stroke on imaging
; sx resolve <24 h (most <1 h) • Ddx: seizure, migraine, hypoglycemia, amyloid spells, TGA, anxiety • Risk of subsequent stroke per
ABCD
²
:
A
ge ≥60 y (+1);
B
P ≥140/90 (+1);
C
lin features: unilat. weak. (+2), speech impair. w/o weakness (+1);
D
uration ≥60 (+2) or 10–59 min (+1);
D
M (+1)

risk of stroke at 48 h: low risk (0–3) = 1.0%; moderate (4–5) = 4.1%; high (6–7) = 8.1%

Physical exam

• General: assess for arrhythmias, murmurs, carotid & subclavian bruits, peripheral emboli • Neurologic exam, NIH stroke scale (
http://www.ninds.nih.gov/doctors/NIH_Stroke_Scale.pdf
)
Acute workup (w/in 8 h for anterior and w/in 24 h for posterior circulation)

• Electrolytes, Cr (relevant for contrast); glc, CBC, coags (see exclusion criteria for lysis) • Cardiac biomarkers, 12-lead ECG, tox screen •
STAT CT
to r/o ICH prior to lysis (Se
MRI, faster, more widely available)

early signs: hyperdense artery, loss of gray-white differentiation, edema, insular ribbon

CT can be nl in first hrs after sx onset, not Se for small strokes & brainstem strokes

obtain CT-angio head & neck or CT perfusion if endovascular intervention indicated

Workup to assess for etiology/modifiable risk factors

• Cardiac: Holter to assess for arrhythmias; echo to assess for thrombus or vegetation, w/ bubble study to assess for PFO/atrial septal aneurysm if suspected embolic stroke • Vessel imaging: carotid U/S and Doppler (if no vessel imaging obtained in acute eval) • Labs: lipids, HbA1c, TSH, homocysteine, Lp(a), hypercoag w/u (if <65 y or cryptogenic stroke; ideally drawn before starting anticoag), ESR/CRP, blood cx if s/s systemic infection •
MRI
helpful if dx of stroke unclear (esp. post circ) or to define stroke subtype, age, exact size

DWI
bright/
ADC
dark = earliest finding in acute ischemia (~ w/in mins, up to days)

T2-FLAIR
: hyperintense w/in hrs, persists for wks;
PWI
differentiates irreversibly infarcted core vs. viable penumbra;
T1
fat-sat
(neck vessels) if suspicious for dissection

Acute treatment of ischemic stroke (
NEJM
2011;364:2138;
Stroke
2013;44:870)

•
Thrombolysis (IV)
: tPA 0.9 mg/kg (max 90 mg), w/ 10% as bolus over 1 min, rest over 1 h

consider if onset w/in 4.5 h,  ICH,  contraindic. (incl. current/prior ICH; head trauma or stroke w/in 3 mo; intracranial neoplasm, AVM or aneurysm; recent intracranial/intraspinal surgery; active internal bleeding; noncompressible arterial puncture; ↑ BP; multilobar infarct; plt <100k, INR >1.7, on Xa inhib, PTT >40, glc <50)

0–3 h: 12% absolute ↑ in good neuro outcome (min/no disability), 5.8% absolute ↑ in ICH, trend toward 4% absolute ↓ mortality

3–4.5 h: 7.2% absolute ↑ in good neuro outcome, 1.8% absolute ↑ in ICH,  mortality benefit (nb, trial excluded patients with previous strokes + DM)

tenecteplase 0.25 mg/kg IV bolus promising (
NEJM
2012;366:1099)