Parkinsonian syndrome diagnosed after alpha-synuclein skin test

17 Dec 2024, 15:45 by Katherine Poinsatte, PhD · Parkinson's News Today

A 45-year-old man initially deemed to have depression was later diagnosed with parkinsonian syndrome following a skin biopsy that detected alpha-synuclein, a protein that forms toxic clumps in the brains of people with Parkinson’s disease, according to a case study from researchers in Miami.

After receiving a combination of carbidopa and levodopa — often used to treat Parkinson’s and related conditions — the man’s motor and mental health symptoms eased.

The patient’s subsequent improvement underscores the importance of considering neurodegenerative etiologies [causes] in patients with atypical or treatment-resistant psychiatric symptoms,” the researchers wrote, noting that a “diagnosis of neurocognitive and psychiatric disorders, particularly when symptoms overlap significantly, poses a substantial challenge in clinical practice.”

The team reported that the alpha-synuclein skin test — called “a novel diagnostic tool” by the researchers — “ultimately led to the diagnosis of parkinsonian syndrome.”

The case study, “Parkinsonian Syndrome Diagnosed via Novel Alpha-Synuclein Skin Biopsy in a Patient Presenting With Catatonic Symptoms,” was published in the journal Cureus.

Man, 45, had depression plus classic Parkinson’s motor symptoms

One of the classic motor symptoms of Parkinson’s disease is bradykinesia — slowness of movement.

Meanwhile, major depressive disorder, or clinical depression, can cause catatonia, a condition marked by impaired communication, rigidity, and unusual movements or lack of movement, as well as behavior abnormalities.

The significant overlap in symptoms between depression and parkinsonian syndrome or atypical parkinsonism — conditions that share similar symptoms to Parkinson’s disease — can make diagnosis difficult.

“The differential diagnosis of neurocognitive and psychiatric disorders is a complex and often challenging task,” the researchers wrote.

Novel diagnostic tools, such as alpha-synuclein skin tests, can help clinicians distinguish between the two conditions, according to the team.

The formation of toxic clumps mainly containing the protein alpha-synuclein, known as Lewy bodies, is a hallmark feature of Parkinson’s disease, and of Lewy body dementia. These toxic clumps of alpha-synuclein lead to the death of brain cells responsible for making a chemical messenger called dopamine, driving disease symptoms.

In addition to accumulating in the brain, alpha-synuclein protein clumps build up in the skin.

In this case study, a man in his mid-40s went to Mount Sinai Medical Center Behavioral Health Department in Miami Beach with a diagnosis of depression with catatonia and anxiety. His first symptom was slowed body movements that interfered with his job in the music industry.

As part of his treatment by a psychiatrist and in a rehabilitation center, the man was prescribed many medications. However, none of them gave him relief from his symptoms.

“The persistence of symptoms despite psychiatric interventions raised the suspicion of an underlying neurological condition,” the researchers wrote.

Alpha-synuclein skin test ‘pivotal’ in parkinsonian syndrome diagnosis

During his evaluation for depression treatment with electroconvulsive therapy — a procedure that uses a mild electrical current to cause a brief seizure — the patient reported symptoms of depression, anxiety, sleep disturbances, and hallucinations, or sensing things such as visions or sounds that seem real but are not. All of these are known nonmotor symptoms of Parkinson’s disease.

The man had a stooped posture, walked with a shuffling gait, and had slowed movements, the doctors noted. The patient reported difficulty in initiating movements, sometimes “freezing up,” and said he felt as if “[his] feet were made of lead”.

Doctors noted he had cogwheel rigidity, a sign of Parkinson’s, in which the limbs move with small jerky movements. He also exhibited micrographia, a common Parkinson’s symptom characterized by small, cramped handwriting.

The man’s cognitive processes also were affected. He was unable to state the date and also had his attention and recall impaired. His mother noted he repeated questions and forgot to close doors.

At a follow-up weeks later, his movements were worsening. His symptoms included bradykinesia and posture changes. His mother said he “seems frozen. [He] cannot get out of bed.”

The man then was then given the skin biopsy, which tested positive for the presence of alpha-synuclein.

Utilizing innovative and novel diagnostic tools like the alpha-synuclein biopsy can offer valuable insights and inform appropriate treatment plans.

“The positive alpha-synuclein biopsy result was pivotal in distinguishing between catatonia and parkinsonian syndrome, facilitating the initiation of appropriate treatment,” the researchers wrote.

Treatment with carbidopa and levodopa was given for the man’s motor dysfunction, which resulted in his bradykinesia easing and his movements feeling “smoother, not as rigid.” Nuplazid (pimavanserin) treatment, given in parallel, moderately reduced his hallucinations.

“The intricacy of this case emphasizes the need for a multidisciplinary approach in diagnosing and managing patients with overlapping psychiatric and neurological symptoms,” the researchers concluded. “Utilizing innovative and novel diagnostic tools like the alpha-synuclein biopsy can offer valuable insights and inform appropriate treatment plans.”