Autologous stem cells in neurology: is there a future?

Stem cells seem very promising in the treatment of degenerative neurological diseases for which there are currently no or limited therapeutic strategies. However, their clinical application meets many regulatory hurdles. This article gives an overview of stem cells, their potential healing capacities as well as their identified and potential risks, such as tumor formation, unwanted immune responses and the transmission of adventitious agents. As there is no clinical experience with embryonic and induced pluripotent stem cells (as the result of their unacceptable risk on tumor formation), most attention will be paid to fresh autologous adult stem cells (ASCs). To evaluate eventual clinical benefits, preclinical studies are essential, though their value is limited as in these studies, various types of stem cells, with different histories of procurement and culturing, are applied in various concentrations by various routes of administration. On top of that, in most animal studies allogenic human, thus non-autologous, stem cells are applied, which might mask the real effects. More reliable, though small-sized, clinical trials with autologous ASCs did show satisfying clinical benefits in regenerative medicine, without major health concerns. One should wonder, though, why it is so hard to get compelling evidence for the healing and renewing capacities of these stem cells when these cells indeed are really essential for tissue repair during life. Why so many hurdles have to be taken before health authorities such as the European Medicine Agency (EMA) and/or the Food and Drug Administration (FDA) approve stem cells in the treatment of (especially no-option) patients.

Recognition and management of Parkinson's disease during the premotor (prodromal) phase.

Therapeutic strategies in Parkinson's disease (PD) provide control of motor (nigral) and nonmotor (extranigral) symptoms. Nigral dopamine-related signs and symptoms are addressed by supplementation or substitution of cerebral dopamine, and extranigral nondopamine-related symptoms are treated by addressing specific autonomic, neuropsychiatric and sleep dysfunctions. However, the ultimate goal in treating PD is to slow, stop or modify disease progression through early and appropriate intervention. Recognition of the various nonmotor clinical manifestations of PD is critical to early diagnosis and treatment. Disease-modifying drugs, once identified, should be initiated as soon as possible, preferably in the prodromal (premotor) phase of the disease. In this review, clinical signs and symptoms of this phase will be described, as will the (suggested) criteria for diagnosis and optimal initiation of disease-modifying agents. Both symptomatic and disease-modifying agents applicable in the premotor phase of PD will also be addressed.

Efficacy of a physical therapy program in patients with Parkinson's disease: a randomized controlled trial.

OBJECTIVE: To investigate the effects of a physical therapy (PT) program in groups of people with Parkinson's disease (PD). DESIGN: Randomized controlled trial with a crossover design. SETTING: Two outpatient rehabilitation clinics in Boston and Amsterdam, respectively. PARTICIPANTS: Sixty-eight subjects diagnosed with typical, idiopathic PD, Hoehn and Yahr stage II or III, and stable medication use. INTERVENTION: Group A received PT and medication therapy (MT) for the first 6 weeks, followed by MT only for the second 6 weeks. Group B received only MT for the first 6 weeks and PT and MT for the second 6 weeks. MAIN OUTCOME MEASURES: The Sickness Impact Profile (SIP-68), the mobility portion of the SIP-68, the Unified Parkinson's Disease Rating Scale (UPDRS), and comfortable walking speed (CWS) at baseline, 6-week, 12-week, and 3-month follow-up. RESULTS: At 6 weeks, differences between groups were significant for the SIP mobility ( P =.015; effect size [ES]=.55), for CWS ( P =.012; ES=.49), for the activities of daily living (ADL) section of the UPDRS ( P =.014; ES=.45), and for the total UPDRS ( P =.007; ES=.56). The total SIP and the mentation and motor sections of the UPDRS did not differ significantly between groups. Significant differences were found at 3 months compared with baseline for CWS, the UPDRS ADL, and total scores. CONCLUSIONS: People with PD derive benefits in the short term from PT group treatment, in addition to their MT, for quality of life related to mobility, CWS, and ADLs; long-term benefits were found in CWS, UPDRS ADL, and total scores but varied between groups.

Early-stage [123I]beta-CIT SPECT and long-term clinical follow-up in patients with an initial diagnosis of Parkinson's disease.

PURPOSE: Previous studies using dopamine transporter single-photon emission computed tomography (SPECT) to try and distinguish between patients with idiopathic Parkinson's disease (IPD) and patients with atypical parkinsonian syndromes (APS) have mainly focussed on patients with an already established clinical diagnosis of several years' duration. Differences in the pattern of striatal involvement between IPD and APS have been found in only few studies. We hypothesized that distinguishing SPECT features might be most pronounced at an early disease stage, and the purpose of the present study was to investigate this hypothesis. METHODS: The study included 72 patients with an initial clinical diagnosis of IPD, supported by decreased striatal [(123)I]beta-CIT binding on baseline SPECT. In ten patients, the diagnosis was changed to APS over a mean follow-up period of 62 months. We retrospectively compared the patterns of striatal involvement on the baseline SPECT scans between the group of patients (re)diagnosed with APS and the remaining 62 patients in whom a diagnosis of IPD was maintained. RESULTS: In the group of patients with APS, baseline [(123)I]beta-CIT binding in both caudate nuclei was lower than in the group of patients with IPD. In addition, putamen to caudate binding ratios were higher in the group of APS patients. In spite of these differences, individual binding values showed considerable overlap between the groups. CONCLUSION: [(123)I]beta-CIT SPECT scanning in early-stage, untreated parkinsonian patients revealed a relative sparing of the caudate nucleus in patients with IPD as compared to patients later (re)diagnosed with APS. Nevertheless, the pattern of striatal involvement appears to have little predictive value for a later re-diagnosis of APS in individual cases.