Plasma Exchange May Treat Lung Cancer-linked LEMS and PCD

Plasmapheresis, or plasma exchange, may be an effective way of managing small cell lung cancer-associated Lambert-Eaton myasthenic syndrome (LEMS) and paraneoplastic cerebellar degeneration (PCD), combined with peripheral nerve damage, a case report suggests.

The simultaneous development of LEMS and PCD is usually associated with small cell lung cancer (SCLC) — an aggressive type of lung cancer most commonly seen in smokers.

In the reported case, however, PCD developed several months after the onset of LEMS. As such, this case highlights that people with SCLC-induced LEMS should be closely monitored for a potentially delayed onset of PCD and tested for the presence of anti-SOX1 antibodies associated with all three conditions.

The case report study, “Simultaneous paraneoplastic cerebellar degeneration, Lambert-Eaton syndrome and neuropathy associated with AGNA/anti-SOX1 and VGCC antibodies,” was published in the journal Neurological Research and Practice.

When cells in the body become cancerous, the immune system targets and kills them by producing antibodies against the proteins they produce. However, some of these proteins also are made by healthy cells, like those in the nervous system.

As such, this sometimes results in a “cross-wiring” that promotes the production of self-reactive antibodies against the body’s own nervous system. That, in turn, can lead to rare conditions known as paraneoplastic neurological syndromes, which include both LEMS and PCD.

LEMS is associated with the production of self-reactive antibodies against a protein called voltage-gated calcium channel or VGCC, which is found at the contact point between nerve and muscle cells. The result is the loss of muscle contraction and muscle weakness.

PCD, meanwhile, is a condition in which antibodies against tumor cells attack healthy cells in the cerebellum, a motor-controlling brain structure. Anti-VGCC antibodies also have been found in 40% of PCD patients.

The presence of self-reactive antibodies against SOX1, a protein found in cells in the cerebellum, is highly specific for SCLC, and is associated with the development of LEMS and PCD.

Notably, anti-SOX1 antibodies have been associated with those against VGCC, further strengthening a link between SCLC and LEMS and PCD.

Now, researchers at the University Hospital Essen, in Germany, reported the case of a 54-year-old man who developed LEMS after having been diagnosed with SCLC. That was followed by rapidly progressing PCD and peripheral nervous system damage, the symptoms of which were successfully managed with plasma exchange. Of note, the peripheral nervous system controls movement and sensation throughout the body.

The man first complained of painless muscular weakness, dizziness, and swallowing difficulties, which progressed to speech problems, shortness of breath, and the inability to stand up or climb stairs alone two months later. At that point, he then was diagnosed with SCLC-associated LEMS.

Further analysis revealed the presence of anti-VGCC antibodies in his blood. Both the SCLC and LEMS responded well to standard treatments and the patient reached a state of stable remission.

However, nine months later, the man developed rapidly progressing symptoms, which included instability walking, vertigo, and weakness in the upper limbs. At that time, the symptoms were attributed to LEMS, but were later found to likely represent the onset of PCD.

Also at this point, antibodies against both VGCC and SOX1 were found in the patient’s blood.

The man responded poorly to common LEMS treatments, including intravenous immunoglobulin, pyridostigmine, and 3,4-diaminopyridine — sold as Firdapse and Ruzurgi.

Seven months later, his condition worsened. He was unable to stand, exhibited worsened movement instability and speech problems, and struggled with eating and drinking. Further assessments showed signs of cerebellum shrinkage suggestive of PCD, and a new partial paralysis of both upper limbs, which correlated with peripheral motor nerve damage.

Increased levels of anti-Sox1 antibodies were found in the patients’ blood and cerebrospinal fluid, which is the liquid that surrounds the brain and spinal cord. According to the researchers, those findings represented “a potential common cause for the PCD, [LEMS] and [peripheral nerve damage].”

However, the team noted, the cause of the patient’s peripheral nerve damage was not conclusively solved, even though anti-SOX1 antibodies have been previously associated with a similar type of damage.

The man was then treated with five courses of plasmapheresis, or plasma exchange, which is commonly used in autoimmune diseases to remove harmful self-reactive antibodies circulating in the bloodstream.

That treatment resulted in motor improvements, with the patient seeing his ataxia, or lack of movement control, ease. He also regained the ability to sit independently and stand with support. Further improvement was likely prevented by his already pronounced neurodegeneration, the team noted.

Four weeks later, a PET/CT scan revealed a suspected cancer metastasis in one of his adrenal glands, which are the small glands located on top of the kidneys. The researchers believe that metastasis might have triggered the man’s rapid progression. Notably, no new metastases had been detected at his last CT scan follow-up, seven months before the PET/CT scan.

The detection of this potential metastasis may offer another therapeutic approach, “as successful treatment of the metastasis might also improve the symptoms of PCD,” the team wrote.

These findings suggest that “delayed onset of PCD should be considered in SCLC patients with [LEMS], and patients should be tested for AGNA/SOX1-antibodies,” the researchers concluded.