Transcript Title of Study Authors university or hospital affiliation

Lambert Eaton Myasthenic Syndrome:
An Elusive Diagnosis
Julie Silverman, MD and Susan Merel, MD
University of Washington
Background
Lambert Eaton Myasthenic Syndrome (LEMS) is an
uncommon disorder of the neuromuscular junction in
which antibodies are made against presynaptic
voltage-gated calcium channels. Approximately 5070% of people diagnosed with LEMS are found to
have an underlying malignancy. Symptoms of LEMS
include proximal muscle weakness, fatigue and
autonomic dysfunction. Although these symptoms are
well-described, the diagnosis of LEMS can be difficult
to make due to the non-specificity of symptoms as
well as the rarity of the disease. The annual incidence
is 0.48 per million population.
Case Report
A 70-year-old previously healthy woman presented to
her primary care physician with concerns of dyspnea,
orthopnea and peripheral edema. Review of systems
further revealed malaise, fatigue, muscle weakness,
nausea and excessive thirst.
Past Medical History
Hypertension
Hyperlipidemia
Osteoarthritis
Mild mitral insufficiency
Social History
Married
Retired office manager
Lifelong non-smoker
Rare alcohol use
Past Surgical History
Unilateral oophorectomy
Appendectomy
Hysterectomy
Left knee arthroscopy
Left knee arthroplasty
Medications
Atenolol
Losartan
Triamterene-HCTZ
Simvastatin
Omeprazole
Pyridoxine
Flax seed oil
Vitamin C
Family History
Mother died from asthma
Patient underwent extensive cardiopulmonary workup including unremarkable electrocardiogram, transthoracic
echocardiogram, myocardial scintigraphy study, chest CT scan and pulmonary function tests.
Patient's symptoms continued, with worsening dry mouth, anorexia and unintentional fifteen-pound weight loss
over the next two months. An EGD, colonoscopy, abdominal ultrasound and abdominal CT scan were obtained,
all of which were unrevealing.
Over the next several months, the patient was hospitalized five times
at four different hospitals. The chief complaints included nausea and
vomiting, difficulty swallowing and profound fatigue.
She was seen by a variety of specialty services, including neurology,
gastroenterology, otolaryngology, speech therapy and rehabilitation
medicine. More diagnostic studies were performed, including a barium
swallow study, esophageal manometry, laryngoscopy, head and neck
CTs and repeat chest, abdomen and pelvis CT scans.
Concerned that depression might be the cause of the patient's symptoms, patient's primary care provider
started her on a selective serotonin reuptake inhibitor (SSRI). Patient denied improvement in symptoms with
SSRI.
Patient was ultimately admitted to the University of
Washington with severe hyponatremia (Na 112 mEq/L),
due to hypovolemia and SSRI-induced SIADH. Despite
normalization of sodium, patient’s symptoms of
weakness, malaise and autonomic dysfunction continued,
prompting further investigation. An electromyogram
(EMG) with repetitive stimulation was performed, which
showed a disorder of presynaptic neurotransmission
consistent with LEMS.
Patient underwent extensive malignancy workup –
including CT chest, abdomen, pelvis, PET scan and
serum tumor markers – which returned negative. She
was started on pyridostigmine and 3,4-DAP with
subjective improvement in symptoms within days of
starting treatment.
Discussion
This case illustrates the potential difficulty of
diagnosing LEMS. At time of her diagnosis, which
was six months after initial presentation, the patient
had been hospitalized at five different institutions,
undergone more than a dozen studies and
procedures and had been evaluated by at least six
different subspecialty services.
LEMS is important to consider in older patients
presenting with weakness and autonomic
dysfunction. While the prevalence of LEMS is low,
recognition of this syndrome is critical, as up to
seventy percent of patients with LEMS have an
underlying malignancy. Additionally, treatment can
be quite effective in reducing symptoms.