MG and LEMS overlap syndrome

MG and LEMS overlap syndrome

Young-Min Lim, MD

Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

History

„ In 1999, a 48-year-old woman presented with a 2-month history of easy fatigability, drooping of the right eyelid, intermittent diplopia and difficulty swallowing, and limb weakness.

„ The symptoms fluctuated during the day and worsen as the day progressed or when fatigued.

„ She did not report dry mouth, constipation,

blurred vision.

History

„ Her past medical history showed nothing significant.

„ Family history was positive for her younger sister having myasthenia gravis (MG).

Neurologic Examination

1. Normal mentation

2. Cranial nerve examination

„ Ptosis on the right.

„ Fatigability of right eyelid muscle on sustained upward gaze.

„ Isocoric pupils with prompt light reflex

„ Full extraocular movements.

Neurologic Examination

2. Cranial nerve examination

„ Normal strength of masticatory and facial muscles.

„ Normal speech, no dysarthria.

„ Normal swallowing function

„ Normal tongue movement, no atrophy or fasciculation.

Neurologic Examination

3. Motor function

„ No muscle wasting

„ No fasciculation

„ Normal muscle tone

„ Weakness of 5-/5 in neck flexors and extensors

„ Weakness of 4+/5 in proximal arm and leg

muscles.

Neurologic Examination

4. Normal sensory examination 5. Absent deep tendon reflexes

„ Potentiation after brief voluntary contraction of the tested muscles.

6. Normal coordination

Impression

„ Generalized Myasthenia Gravis

„ Lamber-Eaton Myasthenic syndrome

„ R/O Congenital Myasthenic syndrome

Investigations

„ Normal serum creatine kinase and thyroid function.

„ Positive fluorescent antinuclear antibody at 1: 40 with a nucleolar pattern.

„ Elevated acetylcholine receptors (AChR) antibodies at 5.9 nmol/L (normal < 0.15)

„ Voltage gated calcium channel (VGCC) antibody testing was not done.

Investigations

„ Positive edrophonium test with improvement of right ptosis

„ Normal chest CT

„ Extensive investigations, including tumor markers, mammography, gastrofibroscopy, and abdominopelvic CT, for possible

malignancy were negative.

Electrophysiologic Data

1

repetitive nerve stimulation (RNS) test ADM FCU Orb.Oculi

Amplitude of CMAP (mV) 10.60 3.20 1.44

Response at the low rate of simulation (%)

2/sec -13.3 -22.2 -8.3

3/sec -14.2 -13.6 -12.8

5/sec -10.0 -13.6 -7.5

Response at the high rate of stimulation

(50/sec, %) 25.6 178.9

Posttetanic stimulation / post-exercise

5/sec immediately after HRS / post-exercise -2.8 -14.4 -6.8 5/sec 4 minutes after HRS / post-exercise -8.3 -9.0 -18.9

Electrophysiologic Data

Repeat RNS test ADM FCU Orb.Oculi

Amplitude of CMAP (mV) 3.40 0.56 0.37

Response at the low rate of simulation (%)

2/sec -10.5 -16.1 -30.3

3/sec -7.8 -25.0 -28.1

5/sec -2.9 -13.1 -29.7

Response at the high rate of stimulation

(50/sec, %) 194.5 497.2

Posttetanic stimulation / post-exercise

5/sec immediately after HRS / post-exercise -3.7 -13.0 -10.8

LRS of ulnar nerve (3Hz) HRS of ulnar nerve (50Hz)

Diagnosis

Overlap myasthenic syndrome 1. Feature of MG

„ Positive AchR antibodies

„ Positive edrophonium test

„ Good response to anticholinesterase treatment 2. Feature of LEMS

„ Areflexia with facilitation after contraction

„ She was treated with pyridostigmine, prednisolone, azathioprine.

„ Her symptom, including right ptosis and limb weakness, gradually improved with treatment.

Treatment and Progress

„ 4 serial assays for AChR antibodies were persistently positive (range, 6.7 – 7.0 nmol/L).

„ Follow-up chest CT revealed thymic hyperplasia.

„ There was no evidence of malignancy during 10-year follow-up.

Treatment and Progress

Serial AChR-ab and RNS tests

Date AChR-ab (nmol/L)

RNS (ADM) RNS (FCU) CMAP

(mV)

LRS (%)

HRS (%)

CMAP (mV)

LRS (%)

HRS (%)

1999 5.9 10.50 -14.2 25.6 3.20 -13.6 178.9

3.40 -7.8 194.5 0.56 -25.0 497.2

2002 6.7

2003 13.60 -4.5 41.7 3.16 -16.0 38.7

2004 7.0

2007 4.9 -17.0 165 1.0 -13.0 279

2008 6.9

Overlap Myasthenic Syndrome

Review

„ MG and LEMS represent two distinct

autoimmune disorders of the neuromuscular transmission and relatively common.

„ Co-existence of these disorders in the same patient is very rare and still controversial.

„ About twenty four cases with combined MG and LEMS features have been reported.

„ The AChR-ab tested positive in 18 (95%) of 19 tested cases.

„ The VGCC-ab test was positive in 7 (58%) of 12 tested patients.

„ Seven cases with positive AChR-ab and VGCC-ab titers provide immunologic

evidence for overlap myasthenic syndrome.

Oh S.J. Clin Neurophysiol. 2005

Characteristics of Overlap Syndrome

„ Common oculo-bulbar symptoms

„ A good response to edrophonium

„ Positive AchR antibodies

„ Areflexia

„ Positive VGCC antibodies

„ The ‘LEMS triad’ in the repetitive nerve stimulation (RNS) test

„ Absence of small-cell lung cancer (SCLC)