Pocket Medicine: The Massachusetts General Hospital Handbook of Internal Medicine (118 page)

• Endovascular (eg, intra-arterial lysis, thrombectomy): w/o proven benefit over thrombolysis IV alone (
NEJM
2013;368:893, 904, 914); thus still experimental, ? consider for major vascular occlusions (distal ICA, prox MCA, esp basilar given high mortality or disability untreated) • BP: lower to <185/110 to consider lysis; if lyse keep <180/105 × 24 h (consider labetalol or nicardipine), o/w permissive HTN unless >220/120 or sx; if sx HoTN consider vasopressors • Initiate ASA w/in 24–48 h; avoid anticoagulation w/in 24 h of lysis; see below for long-term Rx • Cerebral edema → herniation: often occurs 1–5 d post large MCA or cerebellar strokes, ↑ risk in young. Temporize: elevate HOB >30°; mannitol ± 23% NaCl. Hemicraniectomy ↓ mortality (
Lancet Neurol
2007, 6:215). Neurosurgery consult in select MCA and all large cerebellar strokes.

Secondary stroke prevention (
NEJM
2012;366:1914)

•
Antiplatelet therapy
: different agents likely have similar efficacy

ASA
↓ death & repeat stroke; equal to warfarin in nonembolic stroke (
NEJM
2001;345:1444)

ASA
+
dipyrimadole
: sup to ASA (
Lancet
2006;367:1665), but bid dosing, HA → ↓ compliance

clopidogrel
: marginally sup to ASA, slightly ↑ ICH (
Lancet
1996:348:1329)

cilostazol: superior to ASA, less bleeding (
Lancet Neurol
2010;9:959)

clopidogrel + ASA not more effective than ASA alone and ↑ ICH (
Lancet
2004;364:331)

•
Anticoagulation (AC)
: not routinely indicated

Indications: cardiac/paradoxical emboli (except bacterial endocarditis); long segment extradural dissections; hypercoag state; bridge to CEA in sx carotid stenosis w/ongoing TIAs.

INR goal 2–3 for warfarin. Consider LMWH in Pts w/malignancy.

Hold off on AC
in large strokes for ~2–4 wk given risk of hemorrhagic conversion.

• Long-term SBP target 120–139 mmHg ( 
JAMA
2011;306:2137) • Statin: ↓ recurrent stroke w/ atorvastatin 80 mg, LDL goal <70 (
NEJM
2006;355:549) • Fluoxetine: ? improved motor recovery after 3 mo (
Lancet Neurol
2011;10:123) •
Carotid revascularization

CEA
(
if
surgical morbidity & mortality ≤6%) indicated for:

sx stenosis
70–99% (benefit ↑ for males, >75 y, ≤2 wk from stroke) → 65% ↓ RR of repeat stroke, slight benefit for 50–69% stenosis (
NEJM
1991;325:445;
Lancet
2004;363:915)

asx stenosis
70–90%, <79 y: 50% ↓ RR of repeat stroke (
Lancet
2004;363:1491 & 2010;376:1074)

stenting
: compared w/ CEA, periprocedural risk of stroke ↑ (esp. in elderly) & MI ↓ (although many asx), subsequent rates of stroke similar (
NEJM
2010;363:11;
Lancet
2010;376:1062)

Patent foramen ovale (PFO; in ~27% of population) (
NEJM
2005;353:2361)

• ↑ stroke risk: ≥4 mm separation, R→L shunting at rest, ↑ septal mobility, atrial septal aneurysm • If PFO & stroke/TIA: no benefit of warfarin over ASA (
Circ
2002;105:2625), but consider if at high risk for or has DVT/PE. No sig benefit shown for PFO closure so far, albeit studies small & w/ favorable trends (
NEJM
2012;366:991; 2013:1083 & 1092).

INTRACRANIAL HEMORRHAGE (ICH)

Classification by location

• Hemorrhagic strokes: intraparenchymal hemorrhage (IPH) & subarachnoid hemorrhage (SAH)

• Other ICH: epidural hematoma (EDH) & subdural hematoma (SDH)

Etiologies

• AVM, aneurysm, cerebral venous sinus thrombosis → IPH or SAH

• HTN (basal ganglia, cerebellum, brainstem), cerebral amyloid (lobar), tumor (esp. w/ melanoma, renal cell CA, chorio-CA, thyroid CA) → IPH

• Trauma → all locations (nb, IPH or SAH caused by trauma technically not a stroke)

Clinical manifestations (
Lancet Neurol
2005;4:662;
BMJ
2010;341:c5204)

• ↓ consciousness, N/V, HA, progressive focal neurologic deficits

•
SAH
: thunderclap HA, onset w/ exertion; nuchal pain/rigidity; LOC.
EDH
: initial lucid interval.

Workup

• STAT CT brain, angio (CT-A or conventional) if suspicious for vascular source

• LP to ✓ for xanthochromia if no evidence of ICH on CT and suspicious for SAH

• Coags (PT, PTT, INR)

Management

• Reverse coagulopathies w/ vit K & FFP, goal INR <1.4. Plt goal >100k; no clear evidence for plt transfusion if on ASA but may consider with expanding ICH; DDAVP if uremic.

• HOB elevation to 30–45°; strict BP control w/ arterial line, use nicardipine or labetalol gtt, goal SBP <160, for aneurysmal SAH <140, unless risk for hypoperfusion b/c of crit carotid stenosis

• SAH: surgical clipping vs. endovascular coiling (depending on location, comorbidities) of aneurysm/AVM; nimodipine to ↓ risk of vasospasm (monitor w/ TCDs), seizure Ppx

• Surgical evacuation: any EDH; SDH if >1 cm or rapid expansion; IPH: consider in younger Pts w/ ICH, data controversial, potential benefit in superficial IPH (
Lancet
2005, 365:387)

• Venous sinus thrombosis: start anticoagulation, manage ↑ ICP and seizures as needed

WEAKNESS & NEUROMUSCULAR DYSFUNCTION

PERIPHERAL NEUROPATHIES

Etiologies

•
Mononeuropathy
(one nerve): entrapment, compression, trauma, DM, Lyme.

Commonly seen: median n. (carpal tunnel syndrome); ulnar n. (at elbow or wrist); common peroneal n. (at knee with habitual leg crossing); lateral femoral cutaneous n. (at inguinal ligament).

•
Mononeuropathy multiplex
(axonal loss of multiple, separate, noncontiguous nerves):

vasculitides, sarcoid, DM, Lyme, Sjögren, hereditary neuropathy with pressure palsies

•
Small fiber neuropathy
: (unmyelinated or thinly myelinated nerves): idiopathic, DM, CTD, alcohol, sarcoid, thyroid dysfxn, B
₁₂
defic, paraproteinemia, paraneo, celiac, hered.

•
Polyneuropathy
(multiple symmetric nerves, generally length dependent)

Demyelinating

acute: acute inflammatory demyelinating polyneuropathy (AIDP) = Guillain-Barré

subacute: meds (paclitaxel), paraneoplastic

chronic: idiopathic, DM, CIDP, hypothyroidism, toxins, paraproteinemia, hereditary

Axonal

acute: acute motor axonal neuropathy (AMAN), porphyria, vasculitis, uremia

subacute: DM, meds (cisplatin, paclitaxel, vincristine, INH, ddI), EtOH, sepsis, paraneo.

chronic: DM, uremia, lead, arsenic, HIV, paraproteinemia, B
₁₂
defic

Clinical manifestations

• Weakness, fasciculations, numbness, dysesthesias (burning/tingling), allodynia • ± Autonomic dysfxn (orthostasis, bowel/bladder retention/incontinence, impotence) • Depressed or absent DTRs (may be normal in small fiber neuropathy)

Diagnostic studies

• Distal symmetric polyneuropathy: start w/ Hb
_A1C
or glc tolerance test, B
₁₂
, SPEP + SIEP

• EMG & NCS (often no change in first 10–14 d or in small fiber neuropathy) • Electrolytes, BUN/Cr, CBC, TSH, LFTs, ANA, anti-Ro, anti-La, ESR, HIV, Cu, Lyme titers, genetic testing and heavy metal screening as indicated by clinical history and exam • Autonomic testing/skin bx (small fiber), nerve bx (mononeuropathy multiplex) • MRI if possible radiculopathy or plexopathy (after EMG)

Treatment of neuropathic pain

• Pharmacologic: pregabalin, gabapentin, TCAs (nortriptyline, amitriptyline), SSRIs (duloxetine, venlafaxine), tramadol, topical analgesics (lidocaine, capsaicin), opiates • Nonpharmacologic: transcutaneous electrical nerve stimulation (TENS)

GUILLAIN-BARRÉ SYNDROME (GBS)

Definition & epidemiology

• Acute inflammatory demyelinating polyneuropathy (AIDP)

• Incidence 1–2 per 100,000; most common acute/subacute paralysis

• Precipitants in 60%: viral illness (CMV, EBV, HIV), URI (
Mycoplasma
), gastroenteritis (
Campylobacter
), Lyme, immunizations (no proven risk w/ current), surgery
Clinical manifestations

• Distal sensory dysesthesias and numbness often first symptoms, back pain also common • Ascending symmetric paralysis over hours to days; plateau in 1–3 wk • Hypoactive then absent reflexes

• Resp failure requiring mech vent occurs in 30%; autonomic instability & arrhythmias in 50%

• Fisher variant: ophthalmoplegia, ataxia, areflexia; associated with anti-GQ1b antibodies
Diagnostic studies (results may be normal in first several days)

• LP: albuminocytologic dissociation = ↑ protein w/o pleocytosis (<10 WBCs) seen in up to 50% of Pts in 1st wk, 75% by 3rd wk of symptoms • EMG & NCS: ↓ nerve conduction velocity, conduction block, prolonged F wave latency • FVC & NIF: to assess for risk of respiratory failure (cannot rely on P
_a
O
₂
or S
_a
O
₂
)
Treatment

• Plasma exchange (
Coch Data Syst Rev
2002;2:CD001798) or IVIg of equal efficacy and no additional benefit with both (
Neuro
2012;78:1009), steroids not beneficial • Supportive care with monitoring in ICU setting if rapid progression or resp. failure • Watch for autonomic dysfunction: labile BP, dysrhythmias (telemetry) • Most recover near baseline; axonal variant (~5%) with incomplete recovery; 3–5% mortality

MYASTHENIA GRAVIS

Definition & epidemiology

• Autoimmune disorder with Ab directed against acetylcholine receptor (AChR) in NMJ

• Prevalence: 1 in 7500; affects all ages, peak incidence 20s–30s (women), 60s–70s (men)

Clinical manifestations

• Fluctuating weakness w/
fatigability
(worse w/ repetitive use, relieved by rest)

• Cranial muscles involved early → ocular (ptosis, diplopia) in 50%; bulbar (difficulty

chewing, dysarthria, dysphagia) in 15%. Often later progresses to generalized weakness.