From the Guidelines
The diagnostic approach for a patient presenting with symptoms suggestive of Parkinson's disease should begin with a thorough clinical evaluation, and DaTscan can be used to help confirm dopaminergic deficiency, as stated in the acr appropriateness criteria® movement disorders and neurodegenerative diseases 1.
Diagnostic Approach
The diagnosis of Parkinson's disease is primarily clinical, as no definitive biomarker exists. A thorough clinical evaluation focusing on cardinal motor symptoms: resting tremor, bradykinesia, rigidity, and postural instability is essential. Neuroimaging (MRI) may be performed to rule out other conditions.
- Clinical features of Parkinson's disease include resting tremor, bradykinesia, and rigidity, which are related to progressive degeneration of the dopaminergic neurons in the substantia nigra projecting to the striatum 1.
- DaTscan can help confirm dopaminergic deficiency, which is a characteristic feature of Parkinson's disease 1.
Treatment Approach
Treatment typically starts with levodopa (usually combined with carbidopa as Sinemet), beginning at 25/100 mg three times daily and titrating based on response.
- For younger patients or those with milder symptoms, dopamine agonists like pramipexole (0.125-0.5 mg three times daily) or ropinirole (0.25-1 mg three times daily) may be initiated first to delay levodopa-related motor complications.
- MAO-B inhibitors such as selegiline (5 mg twice daily) or rasagiline (1 mg daily) can be used as monotherapy in early disease or as adjuncts later.
- COMT inhibitors like entacapone (200 mg with each levodopa dose) help extend levodopa's effect.
- Non-pharmacological approaches including physical therapy, exercise, and speech therapy are essential components of treatment.
Disease Management
As the disease progresses, treatment must be adjusted to manage motor fluctuations, dyskinesias, and non-motor symptoms like depression, cognitive impairment, and autonomic dysfunction.
- Deep brain stimulation may be considered for patients with medication-refractory symptoms or severe medication-induced complications.
- The clinical presentation of Parkinson's disease is characterized by resting tremor, bradykinesia, and rigidity, and is related to progressive degeneration of the dopaminergic neurons in the substantia nigra projecting to the striatum, as stated in the acr appropriateness criteria® movement disorders and neurodegenerative diseases 1.
From the FDA Drug Label
The safety and efficacy of Ioflupane I 123 Injection were evaluated in two multicenter, single-arm, open-label studies (Study 1 and Study 2) that enrolled 284 adult patients with suspected PS. In these studies, Ioflupane I 123 Injection image interpretation was compared to a reference clinical diagnostic standard of "PS" or "non-PS" PS consisted of Parkinson's disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). These conditions have been associated with dopaminergic neurodegeneration and Ioflupane I 123 Injection imaging was not designed to distinguish among the conditions Among the non-PS population, subjects with a history of the following conditions were included: vascular parkinsonism, psychogenic parkinsonism, essential tremor (ET), various forms of tremor, and other non-PS diagnoses; Ioflupane I 123 Injection imaging was not designed to distinguish among these conditions Patients underwent SPECT imaging with a variety of multi-headed cameras or multi-detector single- slice systems 3 to 6 hours after Ioflupane I 123 Injection administration.
The diagnostic approach for a patient presenting with symptoms suggestive of Parkinson's disease involves the use of Ioflupane I 123 Injection imaging to help differentiate between Parkinsonian syndromes (PS) and non-PS conditions.
- Key points:
- Ioflupane I 123 Injection imaging is used to visualize striatal dopamine transporters.
- A normal image is inconsistent with clinical conditions associated with PS, while an abnormal image is consistent with clinical conditions associated with PS.
- The imaging results should be interpreted in conjunction with clinical diagnostic standards.
- Ioflupane I 123 Injection imaging is not designed to distinguish among different types of PS or non-PS conditions. The treatment approach typically involves the use of levodopa therapies, such as carbidopa and levodopa, to help manage symptoms of Parkinson's disease.
- Key points:
- Carbidopa inhibits decarboxylation of peripheral levodopa, allowing more levodopa to be available for transport to the brain.
- The combination of carbidopa and levodopa increases plasma levels and the plasma half-life of levodopa, and decreases plasma and urinary dopamine and homovanillic acid.
- Carbidopa and levodopa tablets have a bioavailability of approximately 99% relative to the concomitant administration of carbidopa and levodopa 2, 3.
From the Research
Diagnostic Approach
- The diagnosis of Parkinson's disease (PD) is primarily clinical, but in cases of diagnostic uncertainty, evaluation of nigrostriatal dopaminergic degeneration (NSDD) by imaging of the dopamine transporter using DaTscan with single-photon emission computed tomography (SPECT) brain imaging may be helpful 4.
- DaTscan imaging can be useful in several clinical scenarios to determine if NSDD is present, including in patients with early subtle symptoms, suboptimal response to levodopa, prominent action tremor, drug-induced parkinsonism, and in patients with lower extremity or other less common parkinsonism clinical presentations 4.
- The use of DAT-SPECT shows some utility in the early diagnosis of PD and differentiation from other non-degenerative parkinsonian disorders, since it can accurately detect the presynaptic dopaminergic deficit 5.
Treatment Approach
- DaTscan imaging changed clinical diagnosis in 39.8% of patients and led to medication therapy changes in 70.1% of patients 4.
- DAT imaging may also have some prognostic value for disease progression, but it has limited value in differentiating among degenerative causes of parkinsonism 5.
- Clinical assessment remains the most important aspect in evaluating these patients, and DAT-SPECT is a sensitive modality to detect nigrostriatal degeneration 5.
- The introduction of DaTscan imaging and its utility necessitate the development of clinical recommendations for appropriate use, including cases where PD diagnosis is uncertain, tremor of uncertain etiology is present, and nonmotor and/or supportive symptoms and features associated with PD are present but the classical motor syndrome is absent or atypical 6.
DaTscan Imaging
- The Dopamine Transporter Scan (DaT) is a radionuclear imaging technique which was approved by the FDA to differentiate essential tremor (ET) from Parkinson's disease (PD) 7.
- DaTscan imaging provides an effective tool for assessing striatal dopaminergic deficiency, and its diagnostic sensitivity and specificity are high 6.
- DAT-SPECT imaging has been shown to have high sensitivity/specificity by multiple studies, and it may be useful in several clinical situations, including the diagnosis and differential diagnosis of PD, atypical parkinsonian syndromes, and several other different neurological disorders 5, 8.