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Neurologic Disorders in Pregnancy Raymond Powrie MD FRCP(C) FACP Professor of Medicine, Obstetrics & Gynecology Alpert School of Medicine at Brown University Interim Chief of Medicine Women & 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 women Cluster 0.01% all women in a lifetime Secondary causes Mononeuropathies Carpal Tunnel 5-10% Bell’s 0.057% Obturator Nerve Femoral Neuropathy Peroneal Nerve Compression Meralgia 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 Type Location Pain characteris tics Tension Occipital or band like around head Pressure Frontotemporal, unilateral Throbbin g/pulsatin g Migraine Other characteristics Duration Treatment Prophylaxis for HA>2/week or 2 debilitating/month End of day 30 min to 7 days Paracetamol 1 gm every 6 hours ASA<100 mg /daily Nortriptuline 10-50 mg PO QHS Headaches NSAIDS 1st and 2nd trimester Associated nausea, photophobia. Aura in up to 10-30%. 4-72 hours Paracetamol 1 gm every 6 hours Nortriptyline 10-50 mg PO QHS NSAIDS 1st and 2nd trimester Beta Blockers Codeine, pethidine Metroclopramide/caffeine/parace tamol cocktail prochlorperazine Rebound HA Bilateral Throbbin g or pressure Caffeine withdrawal Bilateral Pulsating Occurs with use of analgesia more than 23 times/week Variable Stop analgesia and consider prophylaxis Avoid analgesia, avoid triggers and consider prophylaxis with nortriptyline or beta blockers 1 hour if caffeine ingested, 7 days if not Resolves with time Maintain consistent caffeine uptake Type Location Pain characteristics Preeclampsia Bilateral Pulsating Hypertensive crisis bilateral Subarachnoid Hemorrhage Other characteristics Duration Treatment Scotomata Epigastric pain Hypertesion Proteinuria Intermittent Delivery Throbbing/pulsating BP usually >160/120 Resolves within 1 hour of normalization of BP Gradual lowering of PB Unilateral Abrupt in onset, severe and ‘worst ever’ , incapacitating. Worse with exertion N/V Altered consciousness Days Intervention to treat underlying vascular lesion Cerebral venous thrombosis Diffuse severe Progressive Often neuro deficits Constant Cluster Unilateral periorbital Severe lancinating short lived Tearing, sweating, congestion, edema, miosis, agitation 15-180 minutes Headaches 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 nausea photophobia 1 week Epidural blood patch or IV caffeine Brain tumor Localized Constant Focal neurologic signs Constant Resection Papilledema Visual field defects Intracranial pressure on LP is >200 mm H2O Constant but resolves within 72 hours of normalization of intracranial pressure Lumbar puncture Worse in morning Worse with cough or bending forward Idiopathic intracranial hypertension (‘pseudotumor cerebri’) Diffuse Constant Worse with coughing or val salva 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 nerve Esp. third trimester and with preeclampsia Prednisone 1mg/kg daily for 7 days No 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 MS Disease 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 hygiene Avoid stimulants Avoid amantadine Limb spasticity Worsened in some in pregnancy Physical therapy and benzodiazepines ?Tizanidine Urinary symptoms UTI more likely Baclofen Oxybutinin ? 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 Gravis 1 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 MG Treatment • 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 & AVM Lesion 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 angiogram MRI/MRV Pregnancy risk low Embolization or radiosurgery can be done after pregnancy if warranted Limited 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 CT head read 25 minutes Fibrinolytics (if indicated) •since the time of arrival in the ER •Since the time of onset of symptoms 45 minutes maximum 60 minutes 180 minutes Thrombolysis in Pregnancy Case report: Thrombolytic therapy of a 26 year old pregnant patient The 26 year old patient in her 23rd gestational week noticed weakness of her right arm on awakening. She presented with dense hemiparesis of the right side in the emergency department. Speech was not affected (left handedness). Diffusion weighted MR imaging showed hyperintensity of the left basal ganglia and occlusion of the medial cerebral artery M1 segment (see figure 1). Thrombolytic therapy with alteplase 0.9 mg/kg of body weight for one hour was started. After two hours re-opening of the vessel was seen on transcranial ultrasound. Hemiparesiswas considerably improved. On the following day the right arm paresis deteriorated with leg strength being improved. The MR imaging showed demarcation of an acute ischemic infarction in the basal ganglia and partial re-occlusion of the MCA (see figure 2). No hemorrhage was seen. Cardiotocogram and ultrasound did not show abnormality of the fetus. Further work-up revealed elevated IgG and IgM anti-cardiolipin antibodies (46 GPL-U/m, 8.1 GPL-U/ml, respectively). Anticoagulation with subcutaneous low molecular weight heparin was initiated. The patient was transferred to the rehabilitation unit on day 9. Premature vaginal delivery of a healthy boy occurred in the 32nd + 6 gestational weekwith a birth weight of 2100 grams, (length 43 cm, APGAR 3/7/8, NA-pH 7.00). The boy is reported healthy at one year follow-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