NMS

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

2. 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 100mg qMonth, Seroquel
25mg qhs
• Exam
– BP 145/92, HR 108, T 100.3F
– Awake, nonverbal, follows no requests.
– Axial and appendicular rigidity, no tremor, no
myoclonus

3. 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

4. Case #1: Tests
• CK = 2300 mg/dL

5. Neuroleptic Malignant Syndrome

6. 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

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

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

9. 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

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

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

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

13. Serotonin Syndrome
Management
• Remove offending agent(s)
• Control agitation with benzodiazepines
• 5-HT2A antagonists
– Cyproheptadine 12mg x1, 2mg q2PRN
– IV chlorpromazine or SL olanzapine
• Treat hypotension
• Treat hyperthermia

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

15. Case #3

16. Case #3

17. 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

18. 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

19. Carotid Artery Dissection:
Evaluation and Management
• Tests
– Angiography  gold standard
– MRA neck (fat-suppressed, T1 axial thin cuts)
– CTA neck
• Management
– Improvement is the rule (although 2% recurrence rate)
– Anticoagulation: IV heparin and warfarin
– Antiplatelets?
– Repeat MRA q3-6 months, assess for recanalization

20. 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

21. 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

22. Case 4
Hyperdense basilar artery

23. “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

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

25. 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

26. 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

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

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

29. Case #5

30. 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%

31. 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

32. 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

33. Other Causes of
Spinal Cord Compression
• Trauma
– Steroids
• Bolus: 10-100mg IV dexamethasone
• Maintenance: 4-25mg IV dexamethasone q4h
– Postvoid residual + catheterization
– Neurosurgical consult
• Other causes
– Vascular
– Inflammatory
– Other infections (e.g. TB)

34. Conus Medullaris vs.
Cauda Equina Syndromes

35. Conus Medullaris Syndrome

36. 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 2nd
child after epidural anesthesia.
– In the ED, she had a brief convulsion.

37. 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

38. 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)

39. Emergent Head CT

40. MRV brain MRI brain

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

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

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

44. 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

45. 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

46. 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

47. 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+

48. Case #7
• ABG
– pH 7.31, PaO2 74, PaCO2 52, HCO3 27 mEq/L
• CXR
– Normal
• FVC
– 12 mL/kg

49. 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

50. Myasthenic Crisis: Precipitants

51. Myasthenia and Medications

52. Myasthenic Crisis:
Respiratory Management
• BiPAP trial
– If no hypercapnia
• Intubation and mechanical ventilation
– FVC < 15 mL/kg
– pCO2 > 50 mmHg
– Hypoxemia (late feature)
– Marked bulbar dysfunction

53. 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

54. 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

55. 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

56. Acute Inflammatory
Demyelinating
Polyradiculoneuropathy
(Guillain-Barré Syndrome)

57. AIDP: Tests
• CSF analysis
– WBCs
• Acellular in 90%
• Elevated in 10% (11-50 cells/mm3)
– Lyme, sarcoid, HIV, EBV, neoplastic
– Protein
• Often normal in 1st week
• Increased in 90% by end of the 2nd week

58. 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

59. 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 GQ1b or GT1a antibodies
– Limb weakness infrequent

60. AIDP Variants (2)
• Bickerstaff brainstem encephalitis
– Disturbance of consciousness, hyperreflexia
– Ataxia, ophthalmoplegia
– GQ1b antibodies
– Abnormal brain MRI 30%
• Pharyngeal-cervical-brachial variant
• Acute pandysautonomia
• Pure sensory GBS

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

62. 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, 4th ed.

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

64. 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

65. Case #9
• FLAIR
MRI

66. 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.

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

68. 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

69. Herpes Encephalitis:
Tests
• MRI
– Inferomedial temporal lobe(s) high T2 signal
and enhancement
• EEG
– Focal findings in >80%
• Intermittent high amplitude slow waves
• PLEDs (periodic lateralized epileptiform discharges)
(not pathognomonic but very suggestive)

70. Herpes Encephalitis:
Management
• Antiviral agent: Acyclovir
– 10 mg/kg IV q8 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

71. 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.

72. Thunderclap Headache:
Differential Diagnosis

73. Thunderclap Headache
Initial approach

74. 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, 8th ed.