Epidemiology (Headache 2006;46:365; Lancet Neurol 2013;12:175)
• 1 y HA prevalence is high (40–90%), may be increasing. Most are brief & do not prompt physician visit. Common neuro referral topic. > , slightly. Decreases w/ age.
• 75% of primary HA will ↓ in Preg. ∼40% PP → HA, esp 1st w.
• 90% are tension-type, migraine, or cluster HA. In , 70% are a/w menses, but <20% are pure menstrual migraine.
• Multifactorial initiation. Nociceptor activation/sensitization can → central sensitization, ↑ pain transmission, ↓ pain threshold. Minor role for genetics.
• Primary (most common): Migraine, tension-type HA, cluster, orgasmic HA (elevated estrogen, prolactin, oxytocin)
• Secondary: Ischemic stroke, hemorrhagic stroke (SAH, AVM, HTN), venous sinus thrombosis, carotid or vertebral artery dissection, vasculitides, reversible cerebral vasoconstriction syndromes (Call-Fleming syn [reversible cerebral vasoconstriction], PRES)
• Other: Preeclampsia/eclampsia, benign intracranial HTN, sinusitis, overmedication, PDPH, tumor, estrogen withdrawal, brain tumor
• Primary care: Meningitis, pseudotumor cerebri, trigeminal neuralgia, TMJ syn, temporal arteritis
• Hx: Age, aura, prodrome, frequency, intensity, duration, timing, quality, radiation, assoc sx, FHx, precipitating/relieving factors, changes w/ activity/food/EtOH, resp to rx, visual changes, h/o trauma, change in sleep pattern/exercise/weight/diet/contraceptives, environmental toxins/exposures, menstrual Hx
• Warning signs: Thunderclap HA, autonomic sx, 1st/worst HA of life, worsening, fever, change in mental status/personality, exercise assoc, very young or old age, h/o cancer/Lyme dz/HIV/Preg/PP, *focal neuro findings, *meningismus, *papilledema (* = imaging)
• Physical exam: BP, pulse, auscultation for bruits (neck, temporal), palpation (head, neck, spine), neuro exam w/ fundoscopy
• Labs: Usually not needed; TSH, ESR, CRP, toxicology screen, Lyme Ab, LP (if suspect SAH or infxn)
• Imaging: See warning signs. CT head/c-spine or MR ok. MRI/MRA head/neck if post fossa or vascular suspected.
Treatment and Medications
• 1st line: Relaxation, ice packs, reassurance, acetaminophen, ibuprofen (not Preg). 2nd line: Add narcotics sparingly. 3rd line: Antiemetics (eg, chlorpromazine), IV magnesium. Avoid NSAIDs in 3rd trimester Preg (→ ductus arteriosus closure & oligohydramnios). Other treatments, see below.
• Tension-type HAs: Stress reduction, warm showers, massage, ice/heat packs, posture correction, physical therapy, prescription eyeglasses. NSAIDs, ASA, Tylenol, caffeine, muscle relaxants. Tricyclics for prevention.
Definition & Epidemiology
• Recurring syn of HA, nausea, vomiting, &/or other sx of neurologic dysfxn. Migraine w/ aura = visual sx occur/resolve w/ HA, risk factor for ischemic stroke.
• Increases w/ age in : 22% at 20–24 yo; 28% at 25–29 yo; 33% at 30–34 yo; ∼37% for 35–39 yo. Overall ↓ in Preg, but 8% of pregnant women (esp w/ h/o aura) have increased attack frequency.
• Risk for preeclampsia increased w/ HA (Am J Hypertension 2008;21(3):360). 2.4-fold ↑ w/ any HA Hx; 3.5-fold ↑ w/ migraine; 4-fold ↑ w/ migraines during Preg.
• Status migrainosus: >72 h → evaluate for secondary causes
Pathophysiology (Headache 2006;46:S49)
• Brain itself lacks pain receptors, but surrounding meningeal, muscle, skin, vessel, subcutaneous tissue, or mucous membrane inflammation/injury → HA pain
• Hormonal fluctuations in estrogen → menstrual migraine or PP migraine (withdrawal); ↓estrogen → increased in serotonergic tone
• Migraine phases: Prodrome → ± aura → main migraine pain → resolution
• See conservative measures above. Narcotics not 1st line; abortive therapy needed early. Acute therapies used more than 2 d weekly can lead to rebound HA.
• Avoid combined OCPs if h/o migraine w/ aura or age >35 yo & no aura. D/c combination hormonal contraception if severity/frequency of HA increases or in setting of new onset migraine w/ aura.
• Abn discharge of neurons in the CNS; 5–10% of pop affected
• Epilepsy – recurrent seizures, 0.5–1% of pop; 41 cases per 100000 women
• Generalized seizures: Start in both cerebral hemispheres at onset
• Tonic–clonic: 10–20-s tonic phase (constant muscle contraction) followed by 30-s clonic phase (intermittent muscle contraction)
• Absence: Transient lapse of consciousness – no loss of posture, muscle tone
• Myoclonic: Brief contraction, sudden onset
• Atonic: Brief loss of complete muscle tone (also called “drop attacks”)
• Partial/focal seizures: Limited to 1 area of 1 cerebral hemisphere at onset
• Simple: Motor, sensory, or autonomic; no impairment of consciousness
• Complex: Impairment of consciousness + automatisms
• Syncope – no aura; motor manifestations <30 s; no postictal confusion; pt may have pallor & clamminess
• Psychogenic sz – asym limb movements, pelvic thrusting
• Other – metabolic (EtOH, hypoglycemia); migraine, TIA
• Eclampsia – generalized convulsions &/or coma in the setting of preeclampsia & w/o evid of other neurologic conditions. Preg assoc; pt often has elevated BPs, blurry vision, proteinuria, RUQ pain.
• Alcohol withdrawal, ilicit drugs, meds (β-lactams, antidepressants, clozipine)
• Brain tumor; BP (a/w preeclampsia/eclampsia)
• Cerebrovascular dz (subdural hematoma, hypertensive encephalopathy)
• Degen disorders (Alzheimer’s)
• Electrolyte imbalance (HoNa, hypoglycemia)
• Aura – premonition, abn smells, tastes, oral automatism
• Postictal period – can last minutes to hours; slowly resolving period post sz. Pt may be confused, disoriented, lethargic.
• Status epilepticus – state of continuous seizures >30 min or repeated seizures w/o resolution of postictal periods. Assoc complications: Rhabdomyolosis, lactic acidosis, neuronal death.
Workup and Studies
• Obtain collateral Hx from witnesses as pt will often have amnesia of event
• Ask about loss of responsiveness, aura, unusual behavior, loss of autonomic control (urinary or fecal incontinence)
• Evaluate for etiology w/ h/o fever, illness, prev sz; in Preg, elevated BPs, prot in the urine, ext & facial swelling
• Exam to look for focal neurologic abnormalities or evid of injury from sz activity (oropharyngeal or musculoskeletal or secondary head injury & ecchymoses)
• Labs: CBC, CMP, LFTs, toxicology screen, medication levels
• Preg: Preeclampsia labs (CBC, LFTs, BUN/Cr, uric acid, LDH, proteinuria)
Pregnancy Care (Neurol 2006;66:354)
• 500000 WWE are of childbearing age; 3–5 births per 1000 will be to WWE (Neurol 2000;55:S21). Preg w/ AEDs → ↑ IUGR & hypertensive disorders, ↑ CS (Acta Obstet Gynecol Scan 2006;85:643). If sz free for 2 y, consider withdrawal of AEDs at least 6 mo prior to conception.
• Anticonvulsants that Ø steroid levels: Phenobarbitol, primidone, phenytoin, carbamezapine (to lesser extent w/ oxcarbazepine, felbamate, topiramate)
• If OCPs are deemed necessary, use 50 mcg of estrogen component or extended cycle treatments (3 cycles followed by 4-d break)
• Emergency Contraception: Levonorgestrel 1.5 mg separated by 12 h (doubled dose).
• WHO recommends alternative form of contraception: Levonorgestrel IUD, copper IUD, Depo-Provera (a/w decreased sz frequency)
• New onset seizures in a woman w/ preeclampsia, not attributable to other causes
• Accounts for 12% of mat deaths, worldwide (developing countries > developed countries) (Semin Perinatol 2009;33:130). ∼38% occur w/o preceding sx.
• 2% mortality; 23% will require ventilation; 35% have 1 major complication (pulm edema, renal failure, respiratory distress syn, dissem intravascular coagulation, stroke, cardiac arrest, acute respiratory distress syn)
• Seizures occur in 2–3% of pts w/ sev preeclampsia not receiving magnesium ppx; incid 1.6–10 cases per 10000 deliveries
• Distribution by GA:
<20 w GA: Consider molar Preg or antiphospholipid Ab syn
Up to 48-h PP: 5–39%
>48 h PP: 5–17%, think AVM, ruptured aneurysm, carotid artery dissection, or idiopathic sz d/o
Pathophysiology (Am J Obstet Gynecol 2004;190:714)
• Cerebral autoregulation in resp to high systemic BP → vasospasm of cerebral arteries, intracellular edema
• Loss of autoregulation of cerebral bld flow in resp to high systemic BP → hyperperfusion, endothelial damage, extracellular edema
Clinical Manifestations (Obstet Gynecol 2011;118:995)
• HA – cerebral edema (sens to predict eclampsia 0.98 [95% CI 0.87–1]) (Acta Obstet Gynecol Scand 2011;90:564)
• Vision changes – vasospasm of cerebral & retinal vessels
• Neurologic sx – most common premonitory sx (rates vary from 50–90%)
• Full PIERS model – odds ratio of 2.92 for predicting adverse outcomes in preeclampsia; calculator at: piers.cfri.ca/PIERSCalculatorH.aspx (Lancet 2011;377:219)
• Note: Presence of HTN & proteinuria are poor predictors of eclampsia, rare event. See also chaps. 11 and 12 for preeclampsia.
Treatment and Medication
• Drug of choice = magnesium sulfate (calcium channel antagonism) 4–6 g IV bolus then 1–2 g/h. If no IV → 5 g IM in each buttock (10 g total; rpt 3 g alternating buttock q4h). If seizing on magnesium, rebolus 2 g IV. Therapeutic level 4–6 mEq/L.
• 2nd line: Phenytoin: Loading dose by weight (<50 kg = 1000 mg; 50–70 kg = 1250 mg; >70 kg = 1500 mg). Therapeutic level 12–20 mcg/mL. Check 2 h after loading → subseq dose; if <10 mcg/mL → 500 mg IV, if 10–12 mcg/mL → 250 mg. check level q12h.
• 3rd line: Diazepam 5–10 mg IV bolus, rpt q10–15min prn, max 30 mg in 8 h
• Diazepam, phenytoin were a/w increased recurrence of seizures compared w/ magnesium sulfate (Br J Obstet Gynaecol 1998;105:300; N Engl J Med 1995;333)
• Fetal brady occurs during eclamptic sz. Recover mom; no need for urgent CS
• MagPIE trial: International RCT, >10000 w/ at least mild preeclampsia randomized to magnesium sulfate or placebo. Magnesium sulfate decreases relative risk of eclampsia by 58% (95% CI 40–71). No documented adverse effects on mom or baby in short-term or long-term period (Lancet 2002;359:1877; British J Obstet Gynecol 2006;114:300)
STROKE IN PREGNANCY
Epidemiology and Pathophysiology
• Stroke in Preg = 4–26/100000 (3–10/100000, nonpregnant women)
• Most common in 3rd trimester or puerperium, but also ↑ in PP (8.7× for ischemic stroke; 24× for hemorrhagic stroke). ∼10% of all mat deaths.
• Most common cause of stroke in Preg is preeclampsia/eclampsia
• ↑ due to hypercoagulable state of Preg; cerebral endothelial dysfxn
Diagnosis (Obstet Med 2011;4:2)
• Acute: Hx, PE (listen for murmurs, carotid & subclav bruits, & look for signs of periph emboli). Urgent CT, noncontrast, to rule out hemorrhage, followed by CT angio. MRI/MRA w/ gadolinium. Doppler scan of the LE → if negative, then MRV.
• Risk factors: Hypercoagulable state: Lupus anticoagulant, anticardiolipin antibodies, anti-β2 glycoprotein, Factor V Leiden, prothrombin, prot C & S, antithrombin III. Peripartum cardiomyopathy.
Post Reversible Encephalopathy Syn (Mayo Clin Proc 2010;85:427)
• Related to cerebral autoregulation & endothelial dysfxn. Seen in preeclampsia.
• Features: HA, altered consciousness, visual disturbances (hemianopia, visual hallucinations), seizures (often presenting manifestation)
• Radiology: Symmetrical white matter edema in the post cerebral hemispheres, rarely seen on CT, but better depicted on MRI
• Rx: Lower BP, fully reversible w/i days to weeks
Postpartum Cerebral Angiopathy (Am J Obstet Gynecol 2004;191:375)
• Reversible cerebral vasoconstriction syndromes
• Timeline: Few days post deliv. Features: Thunderclap HA, vomiting, seizures.
• Radiology: Multifocal segmental narrowing of cerebral arteries, resolution in 4–6 w
• CSF nml
Cerebral Aneurysm Rupture and SAH (N Engl J Med 1996;335:768)
• Relative risk of intracerebral hemorrhage during Preg & up to 6 w PP is 5.6 times that of the nonpregnant pt
• Surgical rx after SAH during Preg improves mat & fetal outcomes
• Favor vaginal deliv unless aneurysm is diagnosed at term or there has been neurosurgical intervention w/i the week before deliv
CEREBRAL VENOUS THROMBOSIS
Definition and Epidemiology (Stroke 2011;42:1158)
• Thrombosis of the venous sinuses, cerebral veins, or jugular veins
• Represents 2% of all Preg-related strokes; 12/100000 deliveries (Stroke 2011;42:1158). Risk is highest during 3rd trimester & PP.
• Dehyd, puerpurial & PP infxn, thrombophilia inherent to Preg
• Risk increased w/ use of OCPs (22.1-fold increased odds [95% CI 5.9–84.2%]); increased odds for pts w/ thrombophilia (eg, prothrombin gene mut)
• Acute: Brain CT &/or MRI, bubble study & vascular US of the venous sinuses, cerebral veins, or jugular veins–Best is MRI T2 + MRV – better visualization, good detection of brain parenchyma, no radiation. Can evaluate for both thrombosis & stroke (Stroke 2011;42:1158).
• A nml D-dimer, high negative predictive value, low probability of CVT
• Empty delta sign on contrast-enhanced CT (hyperdensity of cortical vein or dural sinus, filling defect) seen in 25–50% of cases
• Venous infarction is flame-shaped
Figure 18.1 Management of cerebral venous thrombosis
MULTIPLE SCLEROSIS IN PREGNANCY
• Immune-mediated demyelinating neurologic condition, characterized by inflamm lesions affecting the brain & spinal cord & resulting in neurologic disability
• Dz classification:
Relapsing-remitting (RR): Manifestations develop in the context of clearly defined acute relapses followed by partial or complete recovery
Secondary progressive: Following an initial RR course, manifestations worsen gradually w/ or w/o superimposed acute relapses
Primary progressive: Manifestations gradually progress from onset w/o relapses
Progressive relapsing: Manifestations gradually progress from onset w/ subseq superimposed relapses
• Occurs in 3:2 ratio of females to males; peak incid of 30 y of age
• Effect of Preg on MS activity (PRIMS Study. N Engl J Med 1998;339:285; Brain 2004;127:1353)
• 70% reduction in relapse risk in the 3rd trimester of Preg in RRMS pts
• 72% relapse in 1st 3 mo PP – a/w relapse in prepregnancy year, relapse during Preg, no association w/ breastfeeding or epidural placement (Brain 2004;127:1353)
• Long-term prog – increasing disability not related to Preg – fullterm Preg can lengthen time to secondarily progressive course (N Engl J Med 1998;339:285)
Diagnosis During Pregnancy and Postpartum
• Most common presenting sx are paresthesia in 1 or more ext, or 1 side of the face, weakness or clumsiness of leg or hand, or visual disturbances (eg, partial blindness, dimness of vision, or scotoma). Optic neuritis has been reported as the 1st symptom of MS in lactating women (Obstet Gynecol 2001;98:902).
• T2-weighted imaging remains the std tool for dx confirmation after 1st trimester
Rx During Preg
• Acute flare: 3–5-d course of high-dose corticosteroids administered IV
• Some corticosteroids cross the placenta. No association w/ prematurity, IUFD, or SABs
• DMT are offered to MS pt experiencing at least 1 relapse per year
• Interferon B–reduces relapse rates by ∼30%; animal, human studies limited, but show no adverse fetal effects–not a/w increased risk of SAB (Exp Cell Res 2011;317:1301; J Neurol 2010;257:2020; Neurol2010;75:1794)
• Natalizumab (monoclonal Ab against VCAM alpha-4-integrin) may be used for more aggressive dz; safety has not been established in Preg – pts should stop drug 3 mo prior to conception
• Fingolimod (modifies receptors involved in vascular genesis); no evid regarding safety in Preg – pts should stop drug 2 mo prior to conception
• IVIG – not licensed as std MS therapy, but beneficial effects reported w/ use during Preg
• 3–5-d course of high-dose corticosteroids (Solu Medrol 1000 mg QD) – protection from relapse for 4 w PP (J Neurol 2004;251:1133)
• DMT can be restarted but protective effects may be delayed for weeks
NEUROPATHIES IN PREGNANCY
Bell’s Palsy (Otolaryngol Head Neck Surg 2007;137:858)
• Definition: Paralysis of the facial nerve – involving V1, V2, V3
• PE: Asym facial expression & unilateral weakness of eye closure
• Epidemiology: 2–4-fold ↑ during Preg, esp 3rd trimester or in 1st-w PP
• Pathophysiology: Increased perineural edema, hypercoagulability (thrombus of vasa-nervorum), relative immunosuppression in Preg
• Association w/ preeclampsia (QJM 2002;95:359)
• Rx: Cort taper; w/ exception of 1st 9 w of Preg
• Definition: Sensory neuropathy that occurs w/ compression of the lateral femoral cutaneous nerve as it penetrates the tensor fascia lata at the inguinal ligament
• Pathophysiology: Expanding abdominal wall & increased lumbar lordosis
• Rx rarely req
Postpartum Compression Neuropathies (Obstet Gynecol 2003;101:279)
• Epidemiology: Reported in 1–8/10000 deliveries
• Femoral neuropathy: Motor loss involving the quadriceps, w/ sparing of adduction; sensory loss involving the anter thigh & most of the medial thigh
• Lateral femoral cutaneous neuropathy: No motor fibers; lateral hip pain w/ paresthesias or hypesthesias over upper outer thigh
• Peroneal neuropathy: Foot drop caused by prolonged squatting sustained knee flexion, pres on the fibular head from stirrups or palmar pres during pushing
• Obturator neuropathies: Uncommon complication of deliv; pt p/w medial thigh pain & adductor weakness
• Risk factors: Fetal macrosomia, malpresentation, sensory blockade, prolonged lithotomy position, prolonged 2nd stage, improper use of leg stirrups & retractors