Overlapping Symptoms Challenge Diagnosis in Rare Co-Occurrence of PD, MG

The combination of Parkinson disease (PD) and myasthenia gravis (MG) is rarely seen in clinical practice, with a prevalence estimated at 3 in 6 million. Complicating matters further, the disparate diseases share many clinical features, making it difficult to recognize co-occurring disease.

In a case report published in Frontiers of Neurology, investigators describe the experience of diagnosing MG in a patient with preexisting PD. The overlapping symptoms between PD and MG can be especially challenging, they wrote. These include fatigue, weakness, dysarthria, and dysphagia.

“As fatigue is a frequent symptom of Parkinson disease, our patient’s weakness did not initially remind us of the pathological fatigue occurring in myasthenia gravis,” the authors said.

In addition to their case report, the investigators reviewed previously reported cases, identifying their similarities and differences. They also explored possible underlying mechanisms of pathogenesis in this unusual comorbidity.

Old man with eye fatigue

Image credit: sebra - stock.adobe.com.jpeg

Present Case

A 74-year-old man with PD was admitted to the hospital due to a poor clinical response to levodopa, the gold standard of anti-parkinsonian therapy. He received his PD diagnosis after a 4-year history of bradykinesia, a cardinal symptom of parkinsonism. Later, he developed ptosis, dysphagia, dysphonia, head drop, and a shuffling gait.

At the time of his admission, the patient presented with bradykinesia, ptosis, facial masking, dysarthria, and head drop.To explore the cause of ptosis, not common in PD, the investigators performed several diagnostic tests to exclude MG. Instead, results confirmed the diagnosis.

Thus, the patient began treatment for MG in addition to PD. Interestingly, although the ptosis and head drop improved significantly within 1 month’s time, his PD symptoms significantly worsened, necessitating increases in his PD treatment.

Previous Cases

The authors noted that in clinical practice, patients with PD may develop fatigue, weakness, gait disturbances, dysphagia, dysarthria, and limitations of eye movement, which are also symptoms of MG. Because of the rarity of PD comorbid with MG, it is difficult to consider a diagnosis of MG in patients who have PD with such symptoms, they said. 

To better understand PD and comorbid MG, the investigators reviewed previously reported cases of co-occurrence, identifying similarities and differences between cases. Specifically, they collected data on a patient’s age at the time PD/MS onset; the first-occurring diagnosis; test results highly suggestive of MG; PD- and MG-related symptoms; whether a patient presented with head drop and, if so, did head drop present as the first or sole symptom of MG; and the patient’s overall response to PD and MG treatment.

Based on their case review, the authors pointed out the following:

• Nearly 80% of patients with both diagnoses were men
• In more than 70% of cases, a diagnosis of PD preceded MG
• Over 75% of patients had generalized MG
• Most patients responded well to MG treatments with anticholinesterase inhibitors or immunosuppressive therapy

Even so, intravenous immunoglobulin or even plasma exchange was required to control symptoms of MG in less than 20% of the cases, they said.

Interestingly, the incidence of head drop in the patients with the comorbid conditions—approximately one-third—was markedly higher that than seen in patients with PD or in MG alone, they added. 

Underlying Pathogenesis

Although PD and comorbid MG may seem like a coincidence, an underlying mechanism of pathogenesis is likely, the investigators noted. They suggested that an imbalance between the neurotransmitters dopamine (PD) and acetylcholine (MG) and the immune system may very well play significant roles in the pathogenesis of co-occurring disease. To substantiate this possibility, they noted the following data from their literature review:   

• The anti-parkinsonian drug trihexyphenidyl (THP) induced or worsened MG symptoms; these symptoms appear to be closely related to higher serum levels of THP
• Pryridostigmine, used to treat MG, appeared to cause an imbalance between dopamine and acetylcholine by increasing acetylcholine levels, thus inducing or worsening parkinsonism
• Patients with an autoimmune disease generally have a 33% increased risk of PD
• Six patients with both PD and MG had a history of autoimmune disease diagnosis, including Graves disease, rheumatoid arthritis, and psoriasis.
• Seventy percent of patients developed MG after the onset of PD; the investigators said that in these cases, it is likely that MG is secondary to the autoimmune mechanism of PD

“As a curable disease, myasthenia gravis should not be neglected when it occurs against the backdrop of Parkinson disease,” the authors concluded. “Head drop and ptosis are not common phenomena in PD, and thus comorbid MG should be suspected in such situations.”

Reference

Zhang Q, Xu E, Li H-F, Chan P, Zhao Z, Ma J. Parkison’s disease and comorbid myasthenia gravis: a case report and literature review. Front Neurol. Published online January 8, 2024. doi:10.3389/fneur.2023.1303434