Neurologic Emergencies September 4 2009 Matthew Robbins MD

Neurologic Emergencies September 4, 2009 Matthew Robbins, MD Assistant Professor of Neurology Montefiore Headache Center Albert Einstein College of Medicine

Case #1 • History – 49 year old man is found lying on the grounds outside of Bronx Psychiatric Center. He is unresponsive to staff members and 911 was called. The day prior he was less talkative than usual. – Meds: Haloperidol decanoate 100 mg q. Month, Seroquel 25 mg qhs • Exam – BP 145/92, HR 108, T 100. 3 F – Awake, nonverbal, follows no requests. – Axial and appendicular rigidity, no tremor, no myoclonus

Case #1: Differential Diagnosis • • infectious causes of fever drug withdrawal syndromes neuroleptic malignant syndrome serotonin syndrome lethal catatonia acute generalized dystonic reaction malignant hyperthermia parkinsonism

Case #1: Tests • CK = 2300 mg/d. L

Neuroleptic Malignant Syndrome

Neuroleptic Malignant Syndrome: Features • Diagnostic triad: – Fever (>99. 0°F) – Altered mental status – Rigidity (“lead pipe”) • Other features: – – Elevated CK Elevated WBC (>10, 000) Autonomic instability (labile BP, HR) Develops over 24 -72 hours • Mortality 4 -22% • N. B. Withdrawal of Levodopa in Parkinson’s can cause NMS

Neuroleptic Malignant Syndrome: Risk Factors • • • Depot drug Affective disorder Genetic predisposition High potency neuroleptics Rapid dose escalation Dehydration

Neuroleptic Malignant Syndrome: Management • Withdraw (or reinstitute, if levodopa) the offending agent • IV hydration +/- urine alkalinization • Look for underlying infection • Bromocriptine 5 mg TID, titrate up as needed • Start Dantrolene 1 to 3 mg/kg (div TID) if rigidity not controlled • Improvement over 10 -13 days • Rechallenge with neuroleptic at 2 weeks the earliest

Case #2 • History – A 41 year old European woman with a history of depression is brought to the ED by her family “acting drunk” for the past 12 hours. She stopped a medication given to her by her psychiatrist back in France 1 week ago, and a bottle of Venlafaxine was found in her purse. • Exam – Next slide

Diagnosis? Boyer E and Shannon M. N Engl J Med 2005; 352: 1112 -1120

Serotonin Syndrome vs. NMS Pelonero AL, Levenson JL, Pandurangi AK. Neuroleptic malignant syndrome: a review. Psychiatr Serv 1998; 49: 1163 -1172.

Drugs and Drug Interactions Associated with the Serotonin Syndrome Boyer E and Shannon M. N Engl J Med 2005; 352: 1112 -1120

Serotonin Syndrome Management • Remove offending agent(s) • Control agitation with benzodiazepines • 5 -HT 2 A antagonists – Cyproheptadine 12 mg x 1, 2 mg q 2 PRN – IV chlorpromazine or SL olanzapine • Treat hypotension • Treat hyperthermia

Case #3 • History – 40 year old woman presents to the ED with new -onset constant left frontal pain for 2 days. • Exam – Next slide

Case #3

Carotid Artery Dissection: Features • Ipsilateral pain – Headache 55 -100% • Can be thunderclap – Neck pain 25% • Horner’s syndrome <50% – No anhidrosis • Pulsatile tinnitus 25% • Cranial nerve palsies 12% – Most common: hypoglossal • Ischemia 50 -95% – Retina – Cerebral

Carotid Artery Dissection: Who is at risk? • Connective tissue disorders 1 -5% – – Ehlers-Danlos Marfan’s Fibromuscular dysplasia Polycystic kidney disease • Family history 5% • Antecedent URI • Minor precipitating event – “beauty-parlor stroke” – Chiropractic manipulation, yoga, Valsalva • Vascular risk factors • Migraine

Carotid Artery Dissection: Evaluation and Management • Tests – Angiography gold standard – MRA neck (fat-suppressed, T 1 axial thin cuts) – CTA neck • Management – – Improvement is the rule (although 2% recurrence rate) Anticoagulation: IV heparin and warfarin Antiplatelets? Repeat MRA q 3 -6 months, assess for recanalization

Case #4 History • 63 RHM awoke in the morning: – Hallucinating (seeing his mother, who has been dead for years) – Worsening confusion – Double vision upon looking up – Ataxia • PMH: smoker, DM, HTN, atrial fibrillation

Case #4 • Exam – BP 189/100 – Drowsy but alert and oriented, fluent – Left homonymous hemianopia – Right ptosis, hypotropia, and exotropia – Bilateral upgaze paresis – Bilateral Babinski signs – Marked gait ataxia

Case 4 Hyperdense basilar artery

• “Top of the basilar” syndrome Features 3 types of manifestations: 1. Oculomotor • Disrupted vertical gaze • Ptosis, dilated pupils (B/L) • Convergence-retraction nystagmus 2. Behavioral • Somnolence • Peduncular hallucinosis • Amnesia 3. Visual • Field deficits • Balint’s syndrome • • Other features seen: ataxia Prognosis: very poor

“Top-of-the-basilar” syndrome Management • Vessel recanalization is the key – IV t. PA – IA t. PA – Mechanical clot retrieval • Short-term anticoagulation? • Antiplatelets?

Case #5 History – 56 yo RHM starting having pain in his upper back 2 weeks ago, after lifting a heavy box in his garage. – Pain initially responded to ibuprofen. – Since yesterday, pain intensified, sweating, numbness of both legs. – PMH: DM, asthma

Case #5 Exam – BP 102/78 HR 91 T 99. 4°F – No focal tenderness – MSE, CN normal – Bilateral mild paraparesis – DTRs 2+ throughout except absent L triceps and B/L Babinski signs – Absent vibration and diminshed pinprick in legs – +Romberg – Spastic gait

Intramedullary vs. Extramedullary Cord Lesions Signs/Symptoms Intramedullary Extramedullary Adapted from Brazis PW, Masdeu JC, Biller J. Localization in Clinical Neurology, 5 th ed, 2006.

Case #5 Tests – WBC 17, 000 – ESR 57 mm/hr – MRI C-spine +/- gadolinium: next slide

Case #5

Spinal epidural abscess • Who is at risk? – Diabetics – Back trauma – IV drug abusers – Alcoholics – Pregnancy – Prior spinal surgery – HIV • Infections – Staph aureus (50 -90%) – MRSA now common – Strep. species (5 -10%) – Gram negative and anaerobic species (13 -17%) – Accompanying infections – Diskitis 80% – Osteomyelitis 65%

Spinal Epidural Abscess • Workup – MRI spine +/- contrast (>CT) – Blood cultures (+) 50% – No LP or myelogram • Management – Call neurosurgery • urgent open surgery • if small: CT-guided drainage – Antibiotics • Vancomycin initially • Ceftriaxone / Ceftazadime / Metronidazole if other sp. considered

Other Causes of Spinal Cord Compression • Neoplasm – Primary tumors • breast, lung, prostate, lymphoma, sarcoma, kidney – Management • • MRI +/- gadolinium Postvoid residual Steroids + XRT Surgery if XRT unsuccessful or instability

Other Causes of Spinal Cord Compression • Trauma – Steroids • Bolus: 10 -100 mg IV dexamethasone • Maintenance: 4 -25 mg IV dexamethasone q 4 h – Postvoid residual + catheterization – Neurosurgical consult • Other causes – Vascular – Inflammatory – Other infections (e. g. TB)

Conus Medullaris vs. Cauda Equina Syndromes

Conus Medullaris Syndrome

Case #6 • History – A 34 year old woman presented to the ED with 3 days of worsening holocephalic headache. – 1 week ago, uncomplicated delivery of her 2 nd child after epidural anesthesia. – In the ED, she had a brief convulsion.

Case #6 • Exam – Normal mental status – Edematous optic disks – L inferior quadrantanopia – flattened L nasolabial fold – Clumsy L hand – Extinction to double simultaneous stimuli on the L – Mildly L hemiparetic gait

Case #6 • Differential diagnosis – Cortical vein / venous sinus thrombosis – Pituitary apoplexy – Post-dural puncture headache / intracranial hypotension ( can cause subdural) – Reversible cerebrovasoconstrictive syndrome (RCVS) – Posterior reversible leukoencephalopathy syndrome (PRES)

Emergent Head CT

MRV brain MRI brain

“Empty Delta” Sign Lee, E. J. Y. Radiology 2002; 224: 788 -789 Copyright ©Radiological

Frequency of Thrombosis of the Major Cerebral Veins and Sinuses Stam J. N Engl J Med 2005; 352: 1791 -1798

Causes of and Risk Factors Associated with Cerebral Venous Sinus Thrombosis Stam J. N Engl J Med 2005; 352: 1791 -1798

Venous Sinus Thrombosis: Clinical Manifestations • Headache >90% – Rarely thunderclap headache • • Seizures 40% Hemorrhagic infarction 40% Focal hemispheric findings Other symptoms by way of: – Cavernous sinus – Deep venous drainage

Venous Sinus Thrombosis: Management • Acute anticoagulation – IV heparin • Chronic anticoagulation – Warfarin – Re-image to assess recanalization in 3 -6 months • Treat underlying cause • Reduce intracranial pressure – Avoid dehydrating treatments

Case #7 History • 30 year old male (no PMH, on no meds) brought to the ED by friends with shortness of breath • First: sore throat for the past 6 days • 3 days ago: increasing weakness in both the upper and lower limbs • 2 days ago: “breathy” voice and trouble chewing • Today: progressive dyspnea on exertion and then at rest

Case #7 Exam • BP 110/80, HR 96, RR 26, afebrile • Normal mental status • Bilateral moderate ptosis • Fluctuating diplopia on extreme horizontal gaze B/L • Breathy speech • Neck flexors, extensors 4/5 • Deltoids, triceps 4/5, quads 5 -/5 • Normal sensation • DTRs 1+

Case #7 • ABG – p. H 7. 31, Pa. O 2 74, Pa. CO 2 52, HCO 3 27 m. Eq/L • CXR – Normal • FVC – 12 m. L/kg

Clinical Features of Neuromuscular Respiratory Failure • • Shortness of breath Staccato speech Inability to count past 20 in a single breath Tachypnea Accessory muscle use Paradoxical breathing Orthopnea

Myasthenic Crisis: Precipitants

Myasthenia and Medications

Myasthenic Crisis: Respiratory Management • Bi. PAP trial – If no hypercapnia • Intubation and mechanical ventilation – FVC < 15 m. L/kg – p. CO 2 > 50 mm. Hg – Hypoxemia (late feature) – Marked bulbar dysfunction

Myasthenic Crisis: Pharmacological Management • IVIg or plasmapharesis – May be equally efficacious • Acetylcholinesterase inhibitors – Hold while respiratory compromise • Corticosteroids – NOT IV acutely, eventually can start PO for maintenance

Case #8 History • 40 year old woman comes to the ED with 5 days of weakness of her legs • Intermittent tingling of toes and finger tips • Past day – arms feel somewhat weak • 2 weeks prior to symptom onset – flu-like illness

Case #8 Examination • Transverse smile • 4/5 proximal and 3+/5 distal muscles • Diminished light touch and pinprick distally • DTRs: – 1+ biceps, brachioradialis – Remainder absent

Acute Inflammatory Demyelinating Polyradiculoneuropathy (Guillain-Barré Syndrome)

AIDP: Tests • CSF analysis – WBCs • Acellular in 90% • Elevated in 10% (11 -50 cells/mm 3) – Lyme, sarcoid, HIV, EBV, neoplastic – Protein • Often normal in 1 st week • Increased in 90% by end of the 2 nd week

AIDP: Tests • Electrodiagnostics – Predominance of demyelinating features • • multifocal conduction block slowing of nerve conduction velocities prolonged distal and F-wave latencies various degrees of denervation – Frequently normal early *not an emergency

AIDP: Variants • Acute motor-sensory axonal neuropathy – severe, fulminant paralysis + sensory loss – incomplete recovery • Acute motor axonal neuropathy – Most closely associated with C. jejuni – Rapid progression • Miller-Fisher Syndrome – Ophthalmoplegia, ataxia, areflexia – Associated with GQ 1 b or GT 1 a antibodies – Limb weakness infrequent

AIDP Variants (2) • Bickerstaff brainstem encephalitis – Disturbance of consciousness, hyperreflexia – Ataxia, ophthalmoplegia – GQ 1 b antibodies – Abnormal brain MRI 30% • Pharyngeal-cervical-brachial variant • Acute pandysautonomia • Pure sensory GBS

AIDP: Management • Nonpharmacological – Telemetry / ICU – Respiratory assessment – Bowel regimen if needed • Pharmacological – IVIg – Plasmapheresis

Case #9 History • 71 year old healthy woman brought to the ED for 2 days of headache and confusion. • When asked, she complained about a diffuse headache, but could not answer questions coherently. Case 5 -24 from Plum and Posner’s Diagnosis of Stupor and Coma, 4 th ed.

Case #9 Exam • Temp 98°F • Mild left hemiparesis • Mild left-sided inattention

Case #9 • A right hemisphere ischemic stroke was suspected, but the CT did not disclose any abnormality, and she was admitted to the stroke service. • The following day, her temp spiked to 102°F. • LP: – 7 WBCs, 19 RBCs – Protein 48, Glucose 103 – normal opening pressure

Case #9 • FLAIR MRI

Case #9 • By this time, she lapsed into a stuporous state, with small but reactive pupils, full roving eye movements, and symmetrically increased motor tone. • She was started on acyclovir. • Despite treatment she developed edema of the right temporal lobe with uncal herniation.

Herpes Encephalitis: Clinical Features • • • Fever near universal Headache >90% Focal neurological deficits Seizures Mortality 20 -30% Behavioral disturbances (if untreated: 70%) Time course – Acute onset (days to 1 week) – Immunosuppressed patients: days to weeks (subacute)

Herpes Encephalitis: Tests • CSF – Pleocytosis (100 -500 WBCs) – Increased RBCs common – Mild high protein, normal glucose – HSV PCR • In brain biopsy specimens: 98% sens. 100% spec. • Can be negative on day 1 or 2 of illness • Stays (+) in >80% by 1 week of therapy

Herpes Encephalitis: Tests • MRI – Inferomedial temporal lobe(s) high T 2 signal and enhancement • EEG – Focal findings in >80% • Intermittent high amplitude slow waves • PLEDs (periodic lateralized epileptiform discharges) (not pathognomonic but very suggestive)

Herpes Encephalitis: Management • Antiviral agent: Acyclovir – 10 mg/kg IV q 8 hours – Treat for 14 to 21 days – Infusion should be slow – Monitor renal function • When to stop Acyclovir if PCR is (-)? – Low clinical suspicion <1% still has HSV – High clinical suspicion 5% still has HSV

Case #10 • A 47 year old hypertensive man awoke one morning with the most severe, holocephalic, pounding headache that he has ever had, and felt quite nauseous. His family called 911. • Physical and neurological exam was normal. • A nonconstrast CT was unremarkable, and he was discharged after feeling somewhat better.

Thunderclap Headache: Differential Diagnosis

Thunderclap Headache Initial approach

Thunderclap Headache: CT vs CSF in Subarachnoid Hemorrhage Time Sensitivity: CT Sensitivity: CSF Xanthochromia Day 0 95% Unclear from 0 -2 hours 100% at 12 hours Day 3 74% 100% 1 week 50% 100% 2 weeks 30% 100% 3 weeks Almost 0% >70% 4 weeks Almost 0% >40% Adapted from Wolff’s Headache, 8 th ed.