There are several conditions that may look like Parkinson’s disease in the early stages, but differ in pathology and severity. What is the current state of affairs in terms of the breakdown of these pathologies and the treatment options for people affected by Parkinson’s plus syndromes?
NICE guidelines recommend that Parkinson’s should be suspected if a patient has tremor, rigidity, slowness, balance problems, and/or gait abnormalities. When such symptoms occur, prompt referral to a specialist is essential. The guidelines also urge relevant professionals to use the UK Parkinson’s Disease Society Brain Bank Criteria when making a diagnosis. However, Prof. Annette Hand, MD, Newcastle, UK, noted that some of the criteria described therein are outdated. However, it is still a standardization that serves its purpose for general use, and the MDS criteria are also helpful.
It is important to review the initial Parkinson’s diagnosis regularly every 6-12 months to see if any of the Parkinson’s Plus features may be developing. This should be communicated to patients from the beginning. Three main diseases that initially look like Parkinson’s disease (PD) but ultimately are not and evolve into more idiosyncratic pathologies and higher severity are:
- Multiple System Atrophy (MSA)
- Progressive supranuclear palsy (PSP)
- Corticobasal degeneration (CBD)
They all have different diagnostic results, life expectancy averaging 5-10 years, rapid progression, limited response to treatment, and specific symptoms that differ from those of Parkinson’s disease.
Diagnostic testing
Both structural (MRI) and functional (PET and SPECT) techniques play a role in diagnostic evaluation, with both performing better on some aspects of the procedure and less well on others. On the functional side, both 18F-dopaand 123I-ioflupane scansshow clear pictures of the differences between the brains of healthy individuals and PD patients. However, decreased dopaminergic function is also seen in all atypical PDs, so these tests are not in themselves sufficient to distinguish between them. There is too much general overlap between the manifestations of the pathologies. Prof. Nicola Pavese, MD, Newcastle, UK, stated that this pathway will not provide the desired answers at the level of diagnosis.
The 18F-FDG PET scan, which allows examination of glucose metabolism in the brain, clearly shows the differences between PD and MSA, with hyperactivity or hypo-metabolism detected due to greater loss of synapses in the striatum of MSA patients. Advanced software can now covary areas of increased and decreased glucose metabolism in the brain, revealing reproducible patterns of activity specific to the disease and assessing disease progression. A study using 18F-FDG-PETshows recognizable patterns specific to PD and all three major forms of atypical PD. Although this is useful, there is currently no standardized application in a clinical setting. Pavese summarized, however, that the lessons learned so far offer hope for the future. You know that these diseases have different pathologies. MSA, Parkinson’s disease, and dementia with Lewy bodies are synucleinopathies, whereas PSP and CBD have misfolded tau protein. Tracers for misfolded proteins are currently more developed in the tauopathies than in the synucleinopathies, but work is being done.
MRI scans usually show normal images in the early stages of PD and MSA. Red flags that can be identified on structural assessment and are indicative of Parkinson’s plus syndromes are putaminal atrophy, putaminal hypointensity, and putaminal slit. Others include atrophy of the pons, atrophy of the cerebellum, and dilation of the fourth ventricle. MRI scans may reveal pathology more localized to the midbrain in patients with PSP, often referred to as King Penguin or hummingbird signs because of their visual appearance; brainstem planimetry may also be measured. Atrophy of the tegmentum of the midbrain results in what is sometimes called the Mickey Mouse sign, although this can be seen in other conditions, so imaging and clinical features must be considered as a whole. In CBD, asymmetric atrophy of the cortex, parietofrontal and occipital areas can be observed. However, these findings are usually only visible on MRI in advanced stages of disease. There are now new MRI sequences that are sensitive to neuromelanin and provide clear images of PD compared with healthy brain scans, but there have been few studies of atypical parkinsonism.
Focus on interdisciplinarity
Kelley Storey, Newcastle (UK) discussed how a care plan needs to be created with appropriate referral to a multidisciplinary team at the outset, with ongoing communication and documentation between the various professionals essential. Collaboration with palliative care is important because it focuses not only on end-of-life care but also on the management of non-motor symptoms.
There is a movement disorders service in Newcastle that runs a clinic every three months for atypical Parkinson’s disease with a regional reach. The clinic consists of three movement disorder neurologists, four PD specialist nurses, a specialized neurophysiotherapist, a neuro S&L therapist, PC counselors, and two PC specialist nurses and one MSA nurse. The team meets regularly to discuss ongoing research studies and potential issues with patients. Then, patients and their families receive direct, one-on-one care to discuss everything from how to take medications to making sure they are connected with the professionals who are responsible for the patient’s condition.
At the beginning, the patient is given a movement disorder questionnaire, which reduces the likelihood that the patient will forget something they want to discuss. Because the clinic is the hub of the following services:
- Support for bladder and bowel emptying
- Sialorrhea treatment
- Social services
- OP
- MSA/PSP/CBS Welfare Associations
- Gastro-PEG team/dietary assistants
- Family doctor
The primary care physician is the key person for continuity of care and the team works with him or her to provide medication and support management. An early red flag to watch for is a lack of response to levodopa. A more recent complication is that many symptoms of MSA overlap with those of Long Covid. Covid test results are recorded accurately to distinguish them, and a DaTscan shows whether a dopaminergic deficit is present, so the totality of historical and current records should give an indication of possible Parkinson’s syndromes.
Source: When is Parkinson’s not Parkinson’s – differential diagnosis; Parkinson’s Academy webinar, 6/24/2022; www.neurologyacademy.org
InFo NEUROLOGY & PSYCHIATRY 2023; 21(1): 36-37.
