Transcript Professor Rounds LSU NEUROLOGY

Professor Rounds
LSU NEUROLOGY
Raisa C. Martínez, PGY-2
29.Nov.12
• Hospital: Ochsner-Kenner Medical Center
 Admission Date: 10/11/12
 Discharge Date: 10/22/12
• Staff Neurologist: Dr. Barton & Dr. Mader
• Fellows: Dr. Obih & Dr. Mukardamwala
Chief Complaint
“My knees are weak.”
History of Present Illness
53 yo. Caucasian, R-handed, male with PMHx of SHF, HTN, HPLD,
DM2, A-fib, CAD, and COPD who presented to the hospital
complaining of progressive weakness in his lower extremities
bilaterally. Patient reported the symptoms developed approximately
3 weeks prior to admission, yet according to family members, these
symptoms had begun to develop 2 months prior. Weakness
developed in both extremities simultaneously and is not ascending
in nature. There is also weakness in the upper extremities bilaterally,
specifically the shoulders, which began shortly after the leg onset.
He endorses that the lower extremity weakness is significantly
worse than the upper extremities. Patient cannot climb the stairs of
his house, and now is only able to walk with a shuffling gait. Denies
any range of motion (ROM) limitations, but does take longer to do
activities of daily living (ADL’s).
• Patient cannot get up from a chair without
assistance.
• Denies sensory episodes of numbness,
tingling, burning or cramping.
• Denies pain, tremors, twitching, swelling,
redness, or tenderness in muscles or
joints.
• Denies backaches, arthritis, or
musculoskeletal trauma.
Review of Systems: (+)
• Gen: Unintentional weight loss (15 lbs in 8 wks.),
decreased appetite, decreased energy, mild jaundice
• CV: lower extremity edema
• Pulm: Shortness of breath (chronic problem, yet now
requiring O2)
• GI: Constipation
• Neuro: decreased/abnormal taste
• Heme: Easy bruising, R shoulder/back hematoma
Review of Systems: (-)
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Gen: No fevers, chills or night sweats, no trauma
Eyes: No changes in vision, photophobia or inflammation
ENT: No dysphagia, epistaxis or tinnitus
CV: No palpitations, chest pain, or claudication, or syncope
Pulm: No cough with or without sputum, no paroxysmal nocturnal
dyspnea, no orthopnea
Endocrine: no heat/cold intolerance, no increased thirst, no hair loss
GI: No N/V, abdominal pain, distension, changes in stool color or
caliber
GU: No dysuria, flank pain, hematuria, changes in frequency, or
erectile dysfunction
Neuro: No HA, dizziness, lightheadedness, LOC, AMS
MSK: No arthralgias, no myalgias
Skin: No rash, insect bite or soft tissue infections
Past Medical History & Chart Check
• Conditions:
 HTN, CAD, SHF (EF 30%), Afib, DM2, HLPD, COPD,
GERD
• Allergies:
 NKDA/NKFD
• Surgeries:
 CABG (‘95 & ‘96)
 AICD (2003)
 Cholecystectomy
• Family Hx:
 Mother (75) CAD
 Father (72) CAD, DM2, HTN
 No hx. of nerve/muscle
disease
• Social Hx:
 Smoke: 2pck/d x 35 years, quit
1 month prior
 EtOH: social events
 Illicit drugs: none
 OTC: none
 Herbs/Remedies: none
 Lives with mother
• Recent Hospitalizations:
 9/30/12 for Coumadin toxicity
and right shoulder hematoma.
 Coumadin stopped
…
• Medications:
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Spiriva 18 mcg
Coreg 25 mg bid
Losartan 50 mg
ASA 81 mg
Plavix 75 mg
Nexium 40 mg
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Amiodarone 100 mg
Simvastatin 40 mg
Ultram 50 mg PRN
Folic acid 800mg
Lasix 40 mg
Physical Exam
• GENERAL: AAO x3, moderately obese, no apparent distress.
• HEENT: atraumatic,+ scleral icterus, no thyromegaly or cervical
lymphadenopathy. Supple neck.
• CARDIOVASCULAR: Irregularly regular rate and rhythm. No
murmurs,rubs, or gallops.
• RESPIRATORY: Minimal bibasilar crackles, poor breath sounds.
• ABDOMEN: Protuberant, NT/ND,+BS, no hepato-splenomegaly.
• EXTREM: + 3 edema bilateral LE, 1+ pulses LE, 2+ UE, Right LE
muscle wasting
• Skin: + mild jaundice, R shoulder hematoma. No rash, petechiae, or
ulcers
Neurologic Exam
• Orientation
 Person, Place, Time
• Memory
 Remote & recent intact
• Language
• Cranial Nerves:
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 No aphasia
• Fund of Knowledge
 Appropriate
 Aware of current events
• Concentration
 Appropriate
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I: Intact (coffee & alcohol swabs)
II:25/20 bilateral, VF intact
II, III: PERRLA
II,IV,VI: EOMI
V1-3: intact bilaterally, clenches and
grinds teeth, +corneal
VII: symmetric facial expression ;
abnormal taste
VIII: AC>BC, no lateralization
IX, X: uvula midline, symmetric
palate elevation, + gag
XI: TPZ 5/5 ; SCM 5/5
XII:tongue midline
Motor
Shoulder abd
RIGHT
3/5
LEFT
3/5
Shoulder add
Upper arm flex
Upper arm ext
Wrist flex
3/5
4/5
4/5
5/5
3/5
4/5
4/5
5/5
Wrist ext
5/5
5/5
Grasp
Finger Spread
Hip Flex
Thigh abd
Thigh add
5/5
5/5
3/5
4/5
4/5
5/5
5/5
3/5
4/5
4/5
Leg flex
Leg ext
Foot dorsiflex
Foot inversion
Sole cupping
Toe ext
Great toe ext
5/5
5/5
5/5
5/5
5/5
5/5
5/5
5/5
5/5
5/5
5/5
5/5
5/5
5/5
…
• DTR’s
 +2 Biceps, Triceps,
Brachioradialis bilateral
 +1 Patellar bilateral
 0 Achilles bilateral
• Babinski:
 Absent
• Coordination/Balance
 No dysmetria, no tremor, no
Romberg
• Gait
 Wide based, shuffling gait
 Extra steps to turn around
 Unable to get up from chair
with arms crossed
• Sensory
 Decreased pinprick bilateral
plantar surfaces
 Otherwise, intact to light
touch, pinprick, vibration,
temperature and joint-position
throughout
Clinical Approach
Differential Diagnosis
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Onset and Duration:
 Hyperacute (24-72 hours)
 Acute (< 1 month)
 Subacute (1 - 6 months)
 Chronic (> 6 months)
Anatomic Classification:
 Fiber type:
 Motor vs sensory
 Somatic vs autonomic
 Fiber size
Distribution
 Symmetry
 Length-dependent
Axonopathy vs myelinopathy (?)
Laboratory Work-Up
• Hematology:
• Chemistry:
95.8
134 105 51 103
4.8 20 1.4
Ca = 8.3
Mg = 2.6
Phos = 3.8
TPr Alb Tbi AST ALT AkP
6.9 2.3 1.3 39 8 82
11.2 10.8 226
18.5
33.5
Iron = 27
Ferritin = 427
Folate = 9.8
Vit B12 = 451
HgA1C = 5.4%
FT4 = 1.14
TSH = 11.6
Lactic acid = 1.4
INR = 2.3
PT = 24.7
PTT = 42.7
CRP = 127
ESR = 42
LDH = 153
Aldo = 3.3
CPK = 12
…
• CSF:
 Clear, 12 mL total
 Gluc = 73 Prot = 29
LDH = 16 Wbc = 0
Rbc = 0
 Cultures : No organisms
 Arbovirus Panel : negative
• Autoimmune:
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ANA: (-)
RF: (-)
Thyroperoxidase: (-)
Thyroglobulin: 8.3
• Infectious
 RPR : (-)
 Hep Panel: (-)
 HIV: (-)
Neuro-imaging
Head CT
• Remote Left posterior frontal lobe and
Right frontal lobe lacunar infarcts
Cervical/Thoracic/Lumbar CT
• Cervical spondylosis C3-C4
• Mild thoracic and lumbar spondylosis
Electrophysiology
Sensory Nerve Conduction:
Onset
Latency
Peak
Latency
Amp
Segment
Latency
Diff
Distance
Conduction Velocity
Sural R.
NR
NR
NR
NR
NR
NR
NR
Sural L.
NR
NR
NR
NR
NR
NR
NR
Median L.
Digit I
4.3 ms
5.5
11µV
Wrist digit
4.3
130mm
31m/s (50)
Digit II
5.0 ms
5.8 ms (3.5)
6µV (20)
Wrist-digit
5.0 ms
160mm
32m/s (50)
Digit III
NR
NR
NR
Wrist-digit
NR
NR
NR
Ulnar L.
Digit V
NR
NR
NR
NR
NR
NR
NR
Nerve/Site
Electrophysiology
Motor Nerve Conduction:
Nerve/Site
Latency
Amplitude
Segment
Latency
Diff
Distance
Conduction
Velocity
Peroneal L.
NR
NR
NR
NR
NR
NR
5.3 (6.7)
19.1
3.5mV (4)
2.3mV
Ankle-Pop
13.8ms
365mm
26ms (40)
NR
NR
NR
NR
NR
Tibial R.
Ankle
Popliteal
Peroneal R.
Ankle
Poplieal
Tibial L
Ankle
Popliteal
Ankle-Fib
6.5 ms (5.8)
0.6mV (4)
Ankle -Pop
Median L
Wrist
Elbow
5.6ms (4.4)
11.3 ms
1.6mV (4)
1.3mV
Wrist-Elbow
5.7 ms
225 mm
39 ms (50)
Ulnar L.
Wrist
Below elbow
Above elbow
3.9 ms (4.5)
9.3 ms
12.1 ms
1.2 mV (7)
0.9mV
1.0mV
Wrist-below Elbow
Below Elbow-Above
Elbow
5.4 ms
2.8 ms
225 mm
100 mm
42 m/s (50)
36 m/s
Electrophysiology
F-Wave Studies:
Nerve
Tibial R.
Tibial L
Median L
Ulnar
M-late ncy
9.1
16
6.9
4.6
F-late ncy
0.8
0.0
1.8
Needle EMG:
Fibs
PW
Fasc
Pattern
0
0
0
2
Rate
Polys
Dur
Amp
1+
Incr
Incr
Biceps brachii L
Vastus lateralis L
Pathology
Muscle Biopsy : Right Deltoid
• Features of Denervation:
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Atrophic angulated fibers
Increased nuclear bags
Increased CD56
Fiber Type 1 (slow) predominance
No necrosis or infiltration
Normal vasculature
Increased intra-fascicular connective tissue
No RRF, normal stainings (Oil Red O, PAS, SDH,
cytochrome, Myophosphorylase, Acid phosphatase)
In Summary…
53 yo. male with subacute progressive,
symmetric, proximal weakness of arms
and legs with associated unsteady gait,
and hyporreflexia.
Nerve conduction revealed a mixed sensory
and motor neuropathy with both axonal
degeneration and demyelination.
Toxic Neuropathy
Amiodarone
Amiodarone
• Di-iodinated benzofuran derivative initially developed in
the 1960s as an anti-anginal agent.
• Later used as a cardiac antiarrhythmic agent in the
management of supraventricular and ventricular
arrhythmias.
• Approved for the treatment of refractory and lifethreatening ventricular arrhythmias.
• Class III antiarrhythmic agent and shares the capacity to
prolong the duration of action potentials and
refractoriness in Purkinje fibers and ventricular muscle
Adverse Effects
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Prevalence of side effects 15% in the first year, 50% long-term therapy
An amphiphilic drug that forms intra-lysosomal lipid complexes in multiple
tissues:
 Pulmonary
 Chronic Insterstitial Pneumonitis, ARDS, Organizing PNA, Amiodarone
phosphoplipid complexes in air-spaces, decreased DLCO
 Thyroid
 Hyperthyroidism or Hypothyroidism
 Incidence affected by underlying thyroid status
 Skin
 Facial “blue man syndrome”
 Ocular
 Corneal microdeposits, optic neuropathy
 Cardiac
 Sinus bradycardia, Prolonged QT, potentiates Warfarin
 Neurologic
Neurotoxicity
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Tremor
 occurring in 43% and 39% in 2 large series
 6 to 10 Hz action tremor, bilateral and symmetric
 clinically indistinguishable from essential tremor
Ataxia
 7% and 37% of cases in these same series
 associated with limb ataxia and other findings clearly suggesting cerebellar
dysfunction
Optic neuropathy
 insidious onset and slow progression of bilateral visual loss
 associated with optic disc swelling
Myopathy
 without associated neuropathy, with a proximal pattern of weakness and
occasional myalgia
Basal ganglia dysfunction
Encephalopathy
Pseudotumor cerebri
Neuropathy
• Clinical Features :
 Symmetric, subacute to chronic, sensorimotor
polyneuropathy
 Proximal or distal weakness
 Large-fiber sensory modalities are typically involved
with or without small fiber dysfunction
 Occasionally, neuropathy is predominantly motor
 Not length-dependent
 Evolution may be rapid, mimicking Guillain-Barré
 Glove-stocking loss of all sensory modalities, depressed
reflexes, and an ataxic gait
• Electro-diagnostic and Lab Features:
 Demyelination and axonal involvement
 Reinnervation features
 “Myopathic” MUP’s rarely seen
 CK levels do not correlate
 CSF is normal
 Helps distinguish from GBS
 Histopathology
 Loss of large and small myelinated axons
 Muscle is less affected than nerve
• Pathogenesis:
 Direct toxic effect on Schwann cells
 Cause of axon loss thoight to be “secondary.”
 Half-life (~53 days) predisposes to widespread drug
accumulation
 Severity and likelihood of developing toxicity
uncertain
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Age or dose not a risk factors
Length of time receiving medication
Medication metabolism?
Dosing strategy of current era
Literature Review
Summary: Retrospective medical record analysis of cardiac patients treated with
amiodarone at Mayo Clinic between 1998-2006. Neurologic effects that might be
attributable to amiodarone were tabulated.
Summary: Three patients developed peripheral neuropathy after taking amiodarone
for more than 18 months. All had high serum concentrations of amiodarone and its
desethyl metabolite; in one patient concentrations in a sural nerve biopsy were 80
times higher than in serum. Peripheral neuropathy is a complication of large doses
of amiodarone taken over long periods.
Summary: Two patients had slightly asymmetric, mixed, but primarily demyelinating
sensorimotor polyneuropathy. One also had a substantial myopathy. The third had an
acute neuropathy resembling GBS. Seemingly CK levels did not correlate with clinical
or EMG evidence of mypathy. Histologic evaluations of peripheral nerves revealed
demyelination, some axon loss and a variable number of characteristic lysosomal
inclusions. After discontinuation of amiodarone, two patients improved and one died
of cardiac arrhythmia.
• Main Treatment :
 DISCONTINUING Amiodarone
 Reversible partially or almost completely in 16 months afterwards
 May lead to death secondary to cardiac
problems
Hospital Course
• Amiodarone was discontinued by the 3rd day of
hospitalization
 Neuropathy:
 Subjective improved strength and energy
 At discharge, able to ambulate 200 feet
 Follow up appointment LSU Neurology-Kenner
 Pleural effusion with interstitial disease,
 PFT: mild restrictive pattern with decreased DLCO
 Hypothyroidism
 Synthroid 50 mcg
 Atrial fibrillation and AICD
 Monitor ICD activations
References
•
Alport A, Sander H. Clinical Approach to Peripheral Neuropathy: Anatomic
Localization and Diagnostic Testing. Continuum 2012; 18:13-38.
•
Martinez-Arizala A, Sobol SM, McCarty GE, et al. Amiodarone neuropathy.
Neurology 1983;33:643-645.
Pulipaka U, Lacomis D, Omalu B. Amiodarone-Induced Neuromyopathy: Three
cases and a review of literature. J Clin Neuromusc Disease 2002;3:97-105.
Fraser Ag, McQueen IN, Watt AH, et al. Peripheral Neuropathy during long-term
high dose amiodarone therapy. J Neurol Neursurg Psychiatry 1985; 48:576-578.
Kang HM, Kang YS, Kim SH, Seong JK, Kang DY, Lee HY, Lee BS. Amiodarone
induced hepatitis and polyneuropathy. Korean Journal of Internal Medicine
2007;22:225-229.
Charness ME, Morady F, Scheinman MM. Frequent neurologic toxicity associated
with amiodarone therapy. Neurology 1984;34:669-671.
Orr C, Ahlskog, E. Frequency, Characteristics, and Risk Factors for Amiodarone
Neurotoxicity. Arch Neurol 2009;66:865-869.
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