Chromosomal radiosensitivity in patients with multiple sclerosis.

Multiple sclerosis is a clinically heterogeneous autoimmune disease leading to severe neurological disability. Although during the last years many disease-modifying agents as treatment options for multiple sclerosis have been made available, their mechanisms of action are still not fully determined. In the present study radiosensitivity in lymphocytes of patients with relapsing-remitting multiple sclerosis, secondary progressive multiple sclerosis and healthy controls was investigated. Whole blood cultures from multiple sclerosis patients and healthy controls were used to analyze the spontaneous and radiation-induced micronuclei in binucleated lymphocytes. A subgroup of patients with relapsing-remitting multiple sclerosis was treated with immunomodulatory agents, interferon ß or glatiramer acetate. The secondary progressive multiple sclerosis patients group was not receiving any treatment. Our results reveal that the basal DNA damage was not different between relapsing-remitting and secondary progressive multiple sclerosis patients, and healthy controls. No differences between gamma-irradiation induced micronuclei frequencies in binucleated cells from relapsing-remitting and secondary progressive multiple sclerosis patients, and healthy controls were found either. Nevertheless, when we compared the radiation induced DNA damage in binucleated cells from healthy individuals with the whole group of patients, a reduction in the frequency of micronuclei was obtained in the patients group. Induced micronuclei yield was significantly lower in the irradiated samples from treated relapsing-remitting multiple sclerosis patients than in healthy controls and relapsing-remitting not treated patients. Intrinsic sensitivity of lymphocytes subpopulations to the apoptotic effect of immunomodulatory treatment could be responsible for this result.

Impaired comprehension of temporal connectives in Parkinson's disease--a neuroimaging study.

Parkinson's disease has been found to impair comprehension of complex sentences. Here we follow up on earlier findings that sentences describing two successive events in the form of "Before B, A" are understood worse by Parkinson patients than sentences in the form of "After A, B". Before-initial sentences express events in an order inconsistent with their actual order of occurrence and therefore require additional computations during comprehension. In a behavioral study we tested whether 28 German Parkinson patients reading 'before'- and 'after'-initial sentences correctly understood the sequence of events. A second functional magnetic resonance imaging study investigated 16 different patients who read sentences while in the scanner. The behavioral study revealed that 'before' sentences were misunderstood with regard to the temporal sequence of events in 53% (controls 6.5%). The imaging study demonstrated a functional network of the caudate nucleus, middle frontal gyrus, medial superior frontal gyrus, parietal lobule and inferior temporal gyrus. This network was dynamically modulated for 'before' compared to 'after' sentences in healthy controls but not in Parkinson patients. The current results suggest that the additional computations required for 'before' sentences are supported by a network with the caudate nucleus as a central element. This network was compromised in Parkinson patients. We propose that dysfunction of the caudate nucleus networks underlies Parkinson patients' difficulty in dealing with complex sentence structures.

Intertemporal choice in Parkinson's disease.

The administration of dopamine agonists in Parkinson's disease has been associated with impulse control disorders, in particular, pathological gambling. In the present investigation, 17 patients with Parkinson's disease without impulse control disorders and 17 matched control participants were offered choices between monetary rewards (ranging between 11 and 80 euros) available immediately and larger rewards (between 25 and 85 euros) available after delays ranging from 7 to 186 days. Participants had a 1-in-6 chance of winning a reward that they chose on 1 randomly selected trial. Assuming a hyperbolic discounting model, k values were estimated from the pattern of participants' choices. Patients were tested twice, once on dopamine agonist medication and once after 12 hours without medication. Patients showed a considerably steeper discounting function than healthy controls independent of medication status, with k values more than 3 times larger than those of controls. This study shows that patients with Parkinson's disease without clinically apparent impulse control disorders nevertheless tend to make impulsive decisions in intertemporal monetary choice. The lack of difference between sessions could be a result either of the persistent effects of dopaminergic therapy or hint at a genuine medication-independent change in intertemporal choice behavior in Parkinson's disease. This needs to be addressed in further studies. The paradigm used is easy to apply and should be used more extensively to describe decision behavior in Parkinson's disease.