Neurologic Disorders in Pregnancy

Raymond Powrie MD FRCP(C) FACPProfessor of Medicine, Obstetrics & Gynecology Alpert School of Medicine at Brown University

Interim Chief of MedicineWomen & Infants Hospital of Rhode Island

Chief Medical Quality Officer Care New England

Condition Prevalence in Pregnancy

Headaches Tension 86% Migraine 2% in pregnancy (0.2 % hospitalized) – 17% of all womenCluster 0.01% all women in a lifetimeSecondary causes

Mononeuropathies

Carpal Tunnel 5-10%Bell’s 0.057%Obturator Nerve Femoral NeuropathyPeroneal Nerve CompressionMeralgia paresthetica

Epilepsy 1-2%

Multiple Sclerosis 0.15

Myasthenia gravis 0.02%

Stroke 0.01% Intracerebral bleeds, subarachnoid hemorrhage, ischemic stroke, Cerebral venous thrombosis

Headaches

Headaches Type Location Pain

characteristics

Other characteristics

Duration Treatment Prophylaxis forHA>2/week or 2 debilitating/month

Tension Occipital or band like around head

Pressure End of day 30 min to 7 days

Paracetamol 1 gm every 6 hours

NSAIDS 1st and 2nd trimester

ASA<100 mg /dailyNortriptuline 10-50 mg PO QHS

Migraine Fronto-temporal, unilateral

Throbbing/pulsating

Associated nausea, photophobia. Aura in up to 10-30%.

4-72 hours Paracetamol 1 gm every 6 hours

NSAIDS 1st and 2nd trimester

Codeine, pethidine

Metroclopramide/caffeine/paracetamol cocktail prochlorperazine

Nortriptyline 10-50 mg PO QHS

Beta Blockers

Rebound HA Bilateral Throbbing or pressure

Occurs with use of analgesia more than 2-3 times/week

Variable Stop analgesia and consider prophylaxis

Avoid analgesia, avoid triggers and consider prophylaxis with nortriptyline or beta blockers

Caffeine withdrawal

Bilateral Pulsating 1 hour if caffeine ingested, 7 days if not

Resolves with time Maintain consistent caffeine uptake

Headaches Type Location Pain characteristics Other characteristics Duration Treatment

Preeclampsia Bilateral Pulsating ScotomataEpigastric painHypertesionProteinuria

Intermittent Delivery

Hypertensive crisis bilateral Throbbing/pulsating BP usually >160/120 Resolves within 1 hour of normalization of BP

Gradual lowering of PB

Subarachnoid Hemorrhage

Unilateral Abrupt in onset, severe and ‘worst ever’ , incapacitating. Worse with exertion

N/VAltered consciousness

Days Intervention to treat underlying vascular lesion

Cerebral venous thrombosis

Diffuse severe ProgressiveOften neuro deficits

Constant

Cluster Unilateralperiorbital

Severe lancinating short lived

Tearing, sweating, congestion, edema, miosis, agitation

15-180 minutes Prednisone High Flow oxygen

Headaches Type Location Pain characteristics Other characteristics Duration Treatment

Post-dural puncture HA

Diffuse Constant but worse with upright position

Neck stiffness, Hyper-aucusis nauseaphotophobia

1 week Epidural blood patch or IV caffeine

Brain tumor Localized Constant

Worse in morningWorse with cough or bending forward

Focal neurologic signs

Constant Resection

Idiopathic intracranial hypertension (‘pseudotumor cerebri’)

Diffuse Constant

Worse with coughing or val salva

PapilledemaVisual field defects Intracranial pressure on LP is >200 mm H2O

Constant but resolves within 72 hours of normalization of intracranial pressure

Lumbar puncture

Acetozolamide

CVT

Cerebral Venous Thrombosis• Pregnancy carries an increased risk of cerebral

venous thrombosis (CVT)• Symptoms (headache and neurological complaints)

classically develop within three weeks after delivery• Causes ~2% of strokes seen in pregnancy– incidence is higher in under-developed countries. – dehydration is an important and preventable additional

risk• Fatality rate ranging from 4 to 36%

Sidebar

CVT

Red Flags• Sudden onset• New-onset • Severe (‘the worst headache of my life’)• Increasing in severity and frequency• Concomitant HIV/ Cancer• Head trauma • Associated neurologic findings including sleepiness or

change in mental status• Fever• Seizures

Mono-Neuropathies

Mononeuropathies Neuropathy Features Etiology Treatment Meralgia paresthetica(lateral femoral cutaneous nerve)

Numbness over upper outer thigh

Compression of groin by gravid abdomen

Resolves in weeks after delivery

Obturator nerve Medial thigh pain & abductor weakness – circumducting wide based gait

Compression of nerve with vaginal delivery

Resolves in months after delivery

Femoral neuropathy ‘knee buckling’ but normal thigh adduction AND sensory loss over the anterior and medial thigh

Lithotomy positioning with sharp flexion of the hip compresses nerve

Recovery over months with physical therapy +/- kneed brace

Peroneal nerve compression

Foot drop with pain and tingling on dorsum of foot and anterolateral leg

Prolonged squatting, sustained knee flexion of pressure on fibular head from stirrups or labor coaches

Recovery over 8 weeks =/- leg brace

Meralgia Paresthetica

Obturator Neuropathy

Femoral Neuropathy

Peroneal Neuropathy

Mononeuropathies Neuropathy Features Etiology Treatment

Bell’s Palsy (C.N. VII)

Assymmetric facial droop 0.057% of pregnancies

Edema of facial nerveEsp. third trimester and with preeclampsia

Prednisone 1mg/kg daily for 7 daysNo antivirals

Carpal tunnel syndrome(median nerve)

Numbness/pain thumb, index and middle finger 5-10% of pregnancies

Edema in carpal tunnel compresses median nerve

Splints

Carpal Tunnel Syndrome

Multiple Sclerosis

Multiple Sclerosis 3.6 per 100 000

• Neuroinflammation and neurodegeneration in brain and spinal cord– Sensory loss in limbs, visual loss, sub-acute motor

loss, double vision and gait disturbance most common

– Variable pace of progression • Relapsing remitting• Secondary progressive• Primary progressive• Progressive relapsing

Pregnancy Effects • Inheritance poorly understood

– 2-3% prevalence in offspring versus 0.1% in general population • No difference in long- term outcome

– Less relapses in pregnancy– Increased relapse in first three months after delivery (double

the rate) • Treatment of relapse

– High dose steroids 3g methylprednisolone IV daily for 3-5 days– Cannot use mitoxantrone or natalizumab– Might use IV immunoglobulin or plasmapheresis but long term

benefits unclear

MSDisease Modifying Agents (DMD)

• Disease modifying agents– best for relapsing remitting type– glatiramer OK but little studied

• Interferon-beta an abortifacient– Recommended to stop preconception

• Extra relapse of 0.2/year off medication • Pregnancy may also help ameliorate

disease course

Symptom Management

Symptoms Pregnancy Effects Treatment in Pregnancy

Fatigue Worsened by fatigue of normal pregnancy

Sleep hygieneAvoid stimulantsAvoid amantadine

Limb spasticity Worsened in some in pregnancy

Physical therapy and benzodiazepines?Tizanidine

Urinary symptoms UTI more likely BaclofenOxybutinin? tolteridine

Postpartum

• Probably no role for IV gammaglobulin prophylaxis

• DMD medications likely compatible with breastfeeding but often deferred– Not restarted in the context of a relapse

Myasthenia Gravis1 in 20000 deliveries

• Chronic autoimmune disorder in which autoantibodies block/destroy acetylcholine receptors (AchR antibodies) causing impaired transmission at neuromuscular junction

Myasthenia Gravis

• Early fatigue in affected SKELETAL muscle – Ocular and extraocular muscles causing diploplia

and ptosis – Can affect muscles of speech, swallowing and

breathing • Does not affect cardiac or smooth (uterine)

muscle

MGTreatment

• Pyridostigmine (an oral cholinesterase inhibitor)– Dose may need to be increased

• Plasmapheresis or IV immunoglobulin• Particularly for “myasthenic crisis”

• Steroids/azathioprine/cyclosporine• Thymectomy

• ideally before a pregnancy to decrease the risk of neonatal MG

MG Medications to Avoid

• Magnesium sulfate• Antibiotics

– Aminoglycosides (e.g. gentamicin)– Macrolides (e.g. ‘- mycin’) – Ampicillin– Fluoroquinilones (e.g. ‘-floxin’)

• Calcium channel blockers (e.g. nifedipine) • Beta-blockers (e.g. labetalol) • Lithium• Iodine contrast• Statins

MG

• Myasthenic crisis – Acute weakness of respiratory muscles requiring ventilation – Don’t decrease steroid dosing precipitously

• Cholinergic crisis– Small pupils, hyper-salivation and bradycardia

• Fetal/ Neonatal MG– In utero: polyhydramnios, arthrogryposis multiplex congenita– Neonatal: non-reassuring fetal heart tracing and neonatal weakness by 24 hours – Breastfeeding on pyridostigmine is fine

• In labor: – Skeletal muscle weakness may affect ability to push– Consider switch of PO pyridostigmine to IM at a dose of 1/3 of the PO dose

Stroke

Raymond Powrie

Professor Medicine and Obstetrics and Gynecology

Brown University

Stroke

• Ischemic 85%– Thrombosis – Embolism – Systemic hypoperfusion

• Hemorrhagic 15%– Intracerebral

• Usually hypertension related– Subarachnoid Hemorrhage (SAH)

• Usually aneurysms and arteriovenous malformations (AVMs)

Stroke in Pregnancy

• Incidence – 11-26 deliveries per 100,000 in pregnancy versus

10.7 per 100,000 in women of reproductive age

Stroke in Pregnancy Timeframe

• Can occur at any time• Greatest risk is probably in the day before and

the days following delivery

Stroke in Pregnancy Risk Factors

• pre-eclampsia (25-40% of all pregnancy related strokes)

• cesarean delivery• OCP• hypertension • hypotension (typically from hemorrhage) • thrombophilia especially the lupus anticoagulant or anticardiolipin• alcohol and recreational drug abuse esp. cocaine• diabetes • sickle cell disease • smoking • heart disease including peripartum cardiomyopathy• hyperemesis and disturbances in electrolyte and fluid balance

Stroke in Preeclampsia

• Can be due to hemorrhage or ischemia• Not always associated with severe

hypertension – One study of 28 patients found a pre-stroke

systolic BP <150-160 was common

Blood Pressures in Pre-eclamptic Patients Who Had a Stroke in Pregnancy

SAH Aneurysms & AVMLesion Diagnostic test Treatment

SAH CT/MRI =/- LP for xanthochromia CT angiogram and coiling (anueurysm) embolization or sterotactic radiosurgery (AVM)

Aneurysms CT angiogram Coiling if >7 mm even in pregnancy Limited second stage

AVM CT angiogramMRI/MRV

Pregnancy risk lowEmbolization or radiosurgery can be done after pregnancy if warrantedLimited second stage

Sidebar

PRES• PRES Reversible posterior leucoencephalopathy syndrome can

occur as a consequence of eclampsia and pre-eclampsia

• Presents with altered alertness and behaviour, seizures and visual loss, headaches and somnolence

• On neuro-imaging, the most common abnormality is white matter oedema seen as hyperintensity on MRI FLAIR images in the posterior cerebral hemispheres– May be more likely to be asymmetric in eclamptic patients

Sidebar

PRES• Comparing ‘TSE FLAIR’ imaging to ‘Diffusion

weighted’ MR imaging is useful in patients with eclampsia to differentiate vasogenic edema from edema caused by ischemia

Acute Stroke Timing

Seen by provider 10 minutes

Neurologic assessment and head CT

25 minutes

CT head read 45 minutes maximum

Fibrinolytics (if indicated) •since the time of arrival in the ER •Since the time of onset of symptoms

60 minutes

180 minutes

Thrombolysis in Pregnancy

Case report: Thrombolytic therapy of a26 year old pregnant patientThe 26 year old patient in her 23rd gestational week noticedweakness of her right arm on awakening. She presentedwith dense hemiparesis of the right side in theemergency department. Speech was not affected (lefthandedness). Diffusion weighted MR imaging showedhyperintensity of the left basal ganglia and occlusionof the medial cerebral artery M1 segment (see figure1). Thrombolytic therapy with alteplase 0.9 mg/kg ofbody weight for one hour was started. After two hoursre-opening of the vessel was seen on transcranial ultrasound.Hemiparesiswas considerably improved. Onthe following day the right arm paresis deterioratedwith leg strength being improved. The MR imagingshowed demarcation of an acute ischemic infarctionin the basal ganglia and partial re-occlusion of theMCA (see figure 2). No hemorrhage was seen. Cardiotocogramand ultrasound did not show abnormalityof the fetus. Further work-up revealed elevated IgGand IgM anti-cardiolipin antibodies (46 GPL-U/m, 8.1GPL-U/ml, respectively). Anticoagulation with subcutaneouslow molecular weight heparin was initiated.The patient was transferred to the rehabilitation uniton day 9. Premature vaginal delivery of a healthy boyoccurred in the 32nd + 6 gestational weekwith a birthweight of 2100 grams, (length 43 cm, APGAR 3/7/8,NA-pH 7.00). The boy is reported healthy at one yearfollow-up.

• rt-TPA (tissue plasminogen activator e.g. alteplase®) can and should be given in pregnancy when indicated

• 28 cases in the literature… 10 for stroke

Cincinnati Prehospital Stroke Scale

• Specificity 88% • Sensitivity 66-100%

STROKE

• S *Ask her to SMILE. • T *Ask her to TALK, to SPEAK A SIMPLE

SENTENCE. (Coherently) (i.e. . . It is sunny out today?

• R *Ask her to RAISE BOTH ARMS

• TRANSFER/RAPID CT AND NEURO CONSULT

Facial Droop

• Have the patient smile or show teeth– Normal: both sides of face move equally– Abnormal: One side of face does not move as well as the other

Arm Drift

• Arm Drift: Patient closes eyes and extends both arms straight out with palms for 10 seconds– Normal: both arms move the same or both arms do not move at all– Abnormal: one arm does not move or one arm drifts downward with the other

Abnormal Speech• Abnormal speech: have the patient say ‘you can’t teach an old

dog new tricks’ – Normal: patient uses correct words with no slurring– Abnormal: patient slurs words, uses the the wrong words or is unable

to speak

Differential Diagnosis Acute Stroke

• Migraine• TIA• Head trauma• Brain tumor• Todd's palsy (paresis, aphasia, neglect, etc. after a seizure

episode)• Functional deficit (conversion reaction)• Systemic infection• Toxic-metabolic disturbances

– hypoglycemia– acute renal failure– hepatic insufficiency– drug intoxication

Stroke versus Migraine Aura

• Can’t really diagnose a migraine the first or even the second time it happens

• Auras are typically– Brief– More likely to be a positive than a negative symptoms

• Wavey lines inv vision versus no vision• ‘Pins and needles’ versus numbness

– Visual>>Perioral sensory>>>Upper Limbs sensory

Stroke versus Migrainous Aura

• Symptoms must be visual, sensory, or speech related• Visual/sensory symptoms should be one sided • Symptoms gradually progress and last 5–60 minutes• Patients with migraine aura should almost always

have had a history of visual symptoms at some time– the scotoma and the zig-zag lines (aka fortification lines)

are typical

Stroke versus Migrainous Aura

• If more than one aura symptom is present, symptoms should occur in succession rather than simultaneously

• Sensory symptoms that progress as a slow march, and the combination of positive ‘pins and needles’ sensation and subsequent numbness, typically lasting 5 to 60 minutes strongly suggest migraine aura

• Migraine aura speech symptoms are still being defined – Comprehension is rarely if ever affected, whereas searching for words

or using wrong words is a typical feature – Dysarticulation is always present