History and exam

Key diagnostic factors

common

history of small cell lung cancer or other malignancy

Cancer is found either at disease onset or subsequently in around 50% of patients with Lambert-Eaton myasthenic syndrome (LEMS).[2]​​[8][9]​​ Small cell lung cancer (SCLC) is the most commonly associated cancer, although an association with lymphoproliferative disorders has also been described.[3] LEMS precedes the diagnosis of SCLC in up to 69% of patients with LEMS.[7] SCLC is subsequently diagnosed in up to 96% of patients within 1 year of diagnosis.[8]

history of autoimmune disorder

Around 27% of patients with nonparaneoplastic Lambert-Eaton myasthenic syndrome exhibit evidence of an additional organ-specific autoimmune disorder.[12] Autoimmune thyroid disease is the most common; vitamin B12 deficiency, rheumatoid arthritis, inflammatory myopathy, and systemic vasculitis have also been observed.

history of cigarette smoking

Around 50% of patients with Lambert-Eaton myasthenic syndrome have underlying cancer, usually small cell lung cancer (SCLC).[2]​​[8][9]​​​ Cigarette smoking is a strong risk factor for SCLC.

family history of autoimmune disease

Organ-specific autoimmune disease has been described in up to 44% of first-degree relatives of patients with autoimmune or nonparaneoplastic Lambert-Eaton myasthenic syndrome.[10]

limb weakness

Weakness begins in the proximal legs, typically hip flexion and hip abduction, with variable progression, and subsequently usually affects the proximal arms. Distal limb muscles may be involved; this is more common in Lambert-Eaton myasthenic syndrome (LEMS) in association with an underlying cancer (CA-LEMS).[1]

dry mouth

Xerostomia is the most frequently encountered autonomic symptom, occurring in up to 78% of patients, and often precedes other symptoms.[1] This may be experienced by the patient as a "metallic taste."

weakness

Objective weakness is usually mild compared with reported symptoms.[3] Typical pattern of weakness is proximal greater than distal limb weakness most prominent in the hip girdle. A "waddling" gait may be noted. Weakness of facial muscles may also be noted; extraocular involvement is relatively less common.

Other diagnostic factors

common

dysarthria

Common, occurring in up to 71% of patients with Lambert-Eaton myasthenic syndrome, although it typically occurs late in the disease course.[1]

areflexia

Tendon reflexes are reduced or absent in most patients, but may be preserved early in the disease. Hypoactive reflexes can often be potentiated by brief, isometric contraction of the appropriate muscle.[2]

ptosis

May be seen in nearly half of patients.[1] This occurs late in the evolution of Lambert-Eaton myasthenic syndrome, whereas ptosis is typically an early symptom of myasthenia gravis.

diplopia

Up to one third of patients with Lambert-Eaton myasthenic syndrome (LEMS) report diplopia.[1] This is seen later in the development of LEMS, whereas it is often reported early in myasthenia gravis.

impotence

Impotence due to autonomic dysfunction occurs in up to 65% of men with Lambert-Eaton myasthenic syndrome.[1]

dysphagia

Reported in up to 43% of patients with Lambert-Eaton myasthenic syndrome. It is an important symptom to recognize, because prominent swallowing difficulty may necessitate more aggressive therapy.[1]

orthostatic hypotension

Indicates autonomic dysfunction.

uncommon

pupillary dilation

Pupils may be dilated and respond poorly to light.

dyspnea

May indicate severe respiratory or bulbar weakness; a neurologic emergency.

cerebellar ataxia

Uncommon in Lambert-Eaton myasthenic syndrome. Presence on examination suggests a more widespread paraneoplastic syndrome associated with anti-Hu antibodies or reduced P/Q type voltage-gated calcium-channels in the molecular layer of the cerebellum and should further prompt aggressive evaluation for small cell lung cancer.[1][21]​​​

Risk factors

strong

underlying small cell lung cancer or other malignancy

Cancer is found either at disease onset or subsequently in around 50% of patients with Lambert-Eaton myasthenic syndrome (LEMS).[2]​​[8][9]​​​ Small cell lung cancer (SCLC) is the most commonly associated cancer, although an association with lymphoproliferative disorders has also been described.[3] LEMS precedes the diagnosis of SCLC in up to 69% of patients with LEMS.[7] SCLC is subsequently diagnosed in up to 96% of patients within 1 year of diagnosis.[8]

coexisting autoimmune disorder

Around 27% of patients with nonparaneoplastic Lambert-Eaton myasthenic syndrome exhibit evidence of an additional organ-specific autoimmune disorder.[12] Autoimmune thyroid disease is the most common; vitamin B12 deficiency, rheumatoid arthritis, inflammatory myopathy, and systemic vasculitis have also been observed.

cigarette smoking

Around 50% of patients with Lambert-Eaton myasthenic syndrome (LEMS) have underlying cancer, usually small cell lung cancer (SCLC).[2][8][9]​​ Cigarette smoking is a strong risk factor for SCLC.

Male predominance in cancer-associated LEMS varies and likely reflects regional sex-based differences in prevalence of tobacco use.

family history of autoimmune disease

Organ-specific autoimmune disease has been described in up to 44% of first-degree relatives of patients with autoimmune or nonparaneoplastic Lambert-Eaton myasthenic syndrome.[10]

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