Recent advances in the assessment and treatment of falls in Parkinson's disease

Falls are among the most incapacitating features of Parkinson's disease. Prevention of falls requires a systematic assessment of all contributing factors (with emphasis on freezing of gait and frontal executive dysfunction), and a multidisciplinary treatment approach tailored to the specific pathophysiology of falls for each individual patient

Freezing of gait in Parkinson's disease: the paradoxical interplay between gait and cognition

Freezing of gait is a disabling episodic gait disturbance common in patients with Parkinson's disease. Recent evidences suggest a complex interplay between gait impairment and executive functions. Aim of our study was to evaluate whether specific motor conditions (sitting or walking) influence cognitive performance in patients with or without different types of freezing

Treatment of patients with MYC rearrangement positive large B-cell lymphoma with R-CHOP plus lenalidomide:results of a multicenter phase II HOVON trial

Patients with MYC-rearrangement positive large B-cell lymphoma (MYC+ LBCL) have an inferior prognosis following standard first-line therapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) compared to patients withoutMYC rearrangement. Although intensive chemotherapy regimens yield higher remission rates, toxicity remains a concern. Lenalidomide is an oral immunomodulatory drug which downregulates MYC and its target genes thereby providing support using lenalidomide as additional therapeutic option for MYC+ LBCL. A phase II trial was conducted evaluating the efficacy of lenalidomide (15 mg day 1-14) in combination with R-CHOP (R2CHOP) in newly diagnosed MYC+ LBCL patients identified through a nationwide MYCFISH screening program. The primary endpoint was complete metabolic response (CMR) on centrally reviewed F-18-fluorodeoxyglucose (F-18-FDG) positron emission tomography (PET)-computer tomography (CT)-scan at end-of-treatment. Secondary endpoints were overall survival (OS), disease free survival (DFS) and event-free survival (EFS). Eighty-two patients with stage II-IV MYC+ LBCL were treated with six cycles of R2CHOP. At end of treatment, 67% (95% Confidence interval [CI]: 58-75) of the patients reached CMR. With a median follow-up of 25.4 months, 2-year estimates for OS, DFS, EFS were 73% (95% CI: 62-82), 75% (95% CI: 63-84) and 63% change to: (95% CI: 52-73) respectively. In this prospective trial for newly diagnosed MYC+ LBCL patients, we found that administering R2CHOP was safe, and yields comparable CMR and survival rates as in studies applying more intensive chemotherapy regimens. Hence, these findings offer new prospects for MYC+ LBCL patients and warrant comparison in prospective randomized clinical trials. This trial was registered at www.clinicaltrialsregister.eu (#2014-002654-39).</p

Gait-related cerebral alterations in patients with Parkinson's disease with freezing of gait

Contains fulltext : 97934.pdf (publisher's version ) (Closed access)Freezing of gait is a common, debilitating feature of Parkinson’s disease. We have studied gait planning in patients with freezing of gait, using motor imagery of walking in combination with functional magnetic resonance imaging. This approach exploits the large neural overlap that exists between planning and imagining a movement. In addition, it avoids confounds introduced by brain responses to altered motor performance and somatosensory feedback during actual freezing episodes. We included 24 patients with Parkinson’s disease: 12 patients with freezing of gait, 12 matched patients without freezing of gait and 21 matched healthy controls. Subjects performed two previously validated tasks—motor imagery of gait and a visual imagery control task. During functional magnetic resonance imaging scanning, we quantified imagery performance by measuring the time required to imagine walking on paths of different widths and lengths. In addition, we used voxel-based morphometry to test whether between-group differences in imagery-related activity were related to structural differences. Imagery times indicated that patients with freezing of gait, patients without freezing of gait and controls engaged in motor imagery of gait, with matched task performance. During motor imagery of gait, patients with freezing of gait showed more activity than patients without freezing of gait in the mesencephalic locomotor region. Patients with freezing of gait also tended to have decreased responses in mesial frontal and posterior parietal regions. Furthermore, patients with freezing of gait had grey matter atrophy in a small portion of the mesencephalic locomotor region. The gait-related hyperactivity of the mesencephalic locomotor region correlated with clinical parameters (freezing of gait severity and disease duration), but not with the degree of atrophy. These results indicate that patients with Parkinson’s disease with freezing of gait have structural and functional alterations in the mesencephalic locomotor region. We suggest that freezing of gait might emerge when altered cortical control of gait is combined with a limited ability of the mesencephalic locomotor region to react to that alteration. These limitations might become particularly evident during challenging events that require precise regulation of step length and gait timing, such as turning or initiating walking, which are known triggers for freezing of gait