Magnetic resonance imaging

There have been several attempts to use this paraclinical test to find and define patients with asymptomatic or very early PD. One study measured the amount of brain atrophy and white-matter hyperintensities compared with healthy individuals [1]. In this study, there was no correlation in the size or number of white-matter changes between early PD patients and healthy controls. In addition, there was no significant difference in the amount of brain atrophy between the early PD patients and normal controls.

Nuclear imaging

There have been several attempts to use nuclear medicine as a reliable method to document or confirm a dopamine-deficient state. Currently, a dopamine transporter scan (DaTscan^TM) is approved for this use. It is able to differentiate PD with essential tremors, PD versus drug-induced parkinsonism, and psychogenic tremor. However, one of the limitations of this imaging modality is the lack of discrimination between PD and atypical parkinsonian syndrome (APS). In 2009, pre- and postsynaptic dopamine was studied in early parkinsonism using single-photon-emission computed tomography (SPECT) with a combination of [¹²³I]ioflupane (I-FP-CIT), which is a presynaptic ligand for dopamine transporter protein, and [¹²³I]-iolopride (I-IBZM), which is a postsynaptic ligand with affinity to the D2 and D3 receptors located at high concentration in the striatum [2]. When compared with healthy controls, both groups had significantly lower baseline I-FP-CIT ratios. However, there was no significant difference between PD patients and APS patients. The presynaptic phase of the study did not correlate with the disease duration, age of onset or Mini Mental Status Examination (MMSE) scores. When evaluating postsynaptic ratios alone with I-IBZM, there was no significant difference between any of the groups. However, the authors found that by combining the presynaptic and postsynaptic analysis, an accuracy of 85% in excluding APS was found.

One study tried to use a combine striatal binding and cerebral influx analysis of dynamic [¹¹C]raclopride positron emission tomography (PET) in an attempt to improve early differentiation between multiple-system atrophy (MSA) and PD [3]. They divided the study population in three groups: healthy controls, PD patients and MSA patients. When comparing the subjects with healthy controls, the investigators found that the PD patients had slightly lower [¹¹C]raclopride binding in the caudate and slightly higher binding in the posterior putamen. The MSA group showed lower binding in the caudate and in the putamen when compared with healthy controls. When comparing the MSA patients with the PD patients, the MSA patients showed decreased binding in the posterior portions of the putamen bilaterally. On statistical parametric mapping analysis, the PD patients had increased [¹¹C]raclopride binding in the median and left insular cortex, temporofrontal areas, striatum and thalamus when compared with healthy controls. On the other hand, the MSA patients, when compared with the control group, showed decreased cerebellar influx. When comparing the PD group with the MSA group, the MSA group showed decreased striatal, ventral mesencephalic, pontine and cerebellar influx. The investigators concluded that using discriminant analysis combining [¹¹C]raclopride striatal gradient analysis and regional [¹¹C]raclopride influx could distinguish MSA and PD patients with accuracy, and that it showed better performance than the more conventional [¹¹C]raclopride conventional PET analysis.

Vitamin D

Vitamin D deficiency has been reported to be more common in patients with PD. A study was design to evaluate whether this vitamin deficiency is due to lack of mobility and exposure to the sun, or whether it is an integral part of the pathophysiology of PD [4]. the study used a blood bank from the placebo arm of the DATATOP (Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism) trial and tested the blood samples for vitamin D levels at baseline and at the endpoint. The authors found a higher prevalence of vitamin D deficiency at baseline compared with other studies. However, when testing the endpoint blood samples, they found that the vitamin D levels were higher than the baseline values. They concluded that vitamin insufficiency or deficiency may have been present before the clinical manifestation of PD and therefore may play a role in the pathogenesis of PD.

Somatostatin

Some PD patients suffer from slow gastric emptying and also have significant nausea. This is more prominent with patients who have fluctuations of symptoms. It is thought that either medications or pathology affecting the vagal afferents may be the reason for this phenomenon. One study aimed to clarify whether or not digestive hormone secretions in untreated early PD patients are regulated by central command, and if digestive hormone dynamics in early PD patients with and without nausea or vomiting change after treatment of PD [5]. The authors measured plasma levels of digestive hormones (somatostatin and gastrin) at baseline and 3 weeks after PD medications had been applied. They found that the somatostatin levels at baseline were significantly increased in PD patients compared with the healthy controls, especially in those patients suffering from nausea and vomiting. The increases in somatostatin blood levels were similar in all the treatment groups. Levels of gastrin, serotonin, epinephrine, norepinephrine, dopamine and arginine vasopressin were not significantly different between all the groups at baseline or at the end point. The authors concluded that the increase in somatostatin secretions in PD is centrally mediated via vagal afferent fibers.

Deep-brain stimulation

Deep-brain stimulation (DBS) is an approved treatment for PD patients who have motor fluctuations. It has been shown to improve patients’ quality of life. However, recently there have been reports of DBS surgery in early PD patients [6–9]. In one of these studies, it was found that early PD patients were more adept than the more advance population at cooperating during surgery and at articulating stimulation effects. This is believed to be because of better tolerability of the “off” period and decreased disability [6]. In an illustrative case report, it was found that there was an improvement in the Unified Parkinson’s Disease Rating Scale (UPDRS) scores over time [7]. The patient showed a 9-point improvement per year; typically, the total UPDRS score worsens by 8–14 points per year in early-stage PD. In addition, focusing only on motor symptoms using the UPDRS-III, it has been shown previously that the usual decline is 1.9–6.7 points per year, while the patient in this study showed only a 2-point decline per year in the “off” state and improved scores in the “on” state. The authors stated that this observation may be an indication that DBS surgery early in the disease may have a disease-modifying effect. However, they also suggested that this reulst may have been due to optimized treatment. In quality-of-life measures, this patient also improvement in the quality-of-life scales. In summary, over a 2-year period, this patient showed improvement in the motor scores of the UPDRS-III and also in quality-of-life measures. In DBS patients, language is known to be affected, with decreased fluency. These are usually advanced PD patients. In early PD patients, a study reported the impact of DBS with regard to language [8]. The authors compared the performance of healthy controls and early PD patients treated with either DBS/medication or medication alone. Patients were assessed on and off treatment, with controls following a parallel testing schedule. The DBS patients showed improved naming of manipulated but not nonmanipulated objects compared both with controls and with patients on medication only. However, the DBS patients performed poorly at grammar but not in lexicon compared with the other two groups. The authors suggested that DBS surgery impacts language in early PD but that this may be specific to grammatical process and not to lexical processes.

Lastly, there was a randomized, double-blinded trial of transcranial electrostimulation in early PD patients [10]. The authors studied the effect of noninvasive transcranial stimulation on the motor and psychological symptoms in early PD. The subjects were treated with 10 days of placebo versus active treatment and were then followed for 14 weeks and assessed using the UPDRS-I and -III. In week 2, the active treatment resulted in a reduction – although nonsignificant – in the UPDRS scores when compared with placebo. Similarly, the anxiety, depression and sleepiness score differences were not significant.