Time estimation and arousal responses in dopa-responsive dystonia.

Dopa-responsive dystonia (DRD) is caused by an impaired dopamine biosynthesis due to a GTP-cyclohydrolase-1 (GCH1) deficiency, resulting in a combination of dystonia and parkinsonism. However, the effect of GCH1 mutations and levodopa treatment on motor control beyond simple movements, such as timing, action preparation and feedback processing, have not been investigated so far. In an active time estimation task with trial-by-trial feedback, participants indicated a target interval (1200 ms) by a motor response. We compared 12 patients tested (in fixed order) under their current levodopa medication ("ON") and after levodopa withdrawal ("OFF") to matched healthy controls (HC), measured twice to control for repetition effects. We assessed time estimation accuracy, trial-to-trial adjustment, as well as task- and feedback-related pupil-linked arousal responses. Patients showed comparable time estimation accuracy ON medication as HC but reduced performance OFF medication. Task-related pupil responses showed the reverse pattern. Trial-to-trial adjustments of response times were reduced in DRD, particularly OFF medication. Our results indicate differential alterations of time estimation accuracy and task-related arousal dynamics in DRD patients as a function of dopaminergic medication state. A medication-independent alteration of task repetition effects in DRD cannot be ruled out with certainty but is discussed as less likely.

Primary Diffuse Large B Cell Lymphoma of Bone: A Single-Center Experience.

Background: Primary diffuse large B-cell lymphoma of the bone (PB-DLBCL) is a rare type of extra-nodal lymphoma. This study aimed to examine the clinical characteristics, outcomes, treatment modalities and risk of central nervous system relapse (CNSR) among adult Jordanian patients with PB-DLBCL. Methods: This retrospective study included patients aged >16 years who were diagnosed with PB-DLBCL and treated at our hospital between 2002 and 2021. Clinical characteristics, treatment modalities, outcomes and CNSR events were extracted from the hospital's data system and analysed. Patients were categorised into unifocal (UF) and multifocal (MF) PB-DLBCL groups according to the number of bone sites involved. The involvement of only one site was defined as UF, whereas the involvement of two or more sites was defined as MF. Results: In total, 12 patients were diagnosed with PB-DLBCL. Their median age was 47.5 years (range, 17-80 years). The male:female ratio was 1:1. There were eight patients in the UF PB-DLBCL group and four in the MF PB-DLBCL group. All patients received treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone. In the UF PB-DLBCL group, the male:female ratio was 5:3, the median age was 41 years, and the follow-up duration was 9-135 (mean, 83.3) months. In the MF PB-DLBCL group, the male:female ratio was 1:3, the median age was 51.5 years, and the survival time was 3-11 (mean, 7) months. Three patients with vertebral UF PB-DLBCL underwent early vertebroplasty without complications. The most common site involved was the vertebral column. Most patients with UF PB-DLBCL achieved complete remission (CR), whereas no patients with MF PB-DLBCL achieved CR. Conclusion: PB-DLBCL is rare in adult Jordanian patients. UF PB-DLBCL is more common than MF PB-DLBCL. Patients with UF PB-DLBCL had a good prognosis. Patients with MF PB-DLBCL had a high international prognostic index score, risk of CNSR and short survival time.

Longitudinal evaluations of somatosensory-motor inhibition in Dopa-responsive dystonia.

INTRODUCTION: GCH1 mutations have been linked to decreased striatal dopamine and development of dopa-responsive dystonia (DRD) and Parkinsonism. Sensory and sensorimotor integration impairments have been documented in various forms of dystonia. DRD patients with confirmed GCH1 mutations have demonstrated normal short-latency afferent inhibition (SAI), a measure of sensorimotor inhibition, under chronic dopaminergic replacement therapy (DRT), but reduced inhibition after a single l-dopa dose following 24 h withdrawal. Studies have revealed normal SAI in other forms of dystonia but reductions with DRT in Parkinson's disease. Longitudinal changes in sensorimotor inhibition are unknown. METHODS: We analyzed sensorimotor inhibition using two different measures: SAI and somatosensory-motor inhibition using dual-site transcranial magnetic stimulation (ds-TMS). SAI was measured using digit stimulation 25 ms prior to contralateral primary motor cortex (M1) TMS. DS-TMS was measured using TMS over the somatosensory cortex 1 or 2.5 ms prior to ipsilateral M1 stimulation. A total of 20 GCH1 mutation carriers and 20 age-matched controls were included in the study. SAI and ds-TMS were evaluated in GCH1 mutation carriers both OFF and ON DRT compared to controls. Furthermore, longitudinal changes of SAI were examined in a subset of the same individuals that were measured âˆ¼five years earlier. RESULTS: Neither SAI nor ds-TMS were significantly different in GCH1 mutation carriers relative to controls. No effects of DRT on SAI or ds-TMS were seen but SAI decreased over time in mutation carriers OFF DRT. CONCLUSION: Our longitudinal results suggest changes in SAI that could be associated with plasticity changes in sensorimotor networks.

ß-Blocker-Induced Tremor.

BACKGROUND: Although the ß-blocker propranolol is considered one of the most effective tremor treatments and other ß-blockers are often prescribed to patients with tremor, those with partial ß-agonist activity on ß-adrenoreceptors can theoretically induce or exacerbate tremor. Here we report 2 patients with tremor induced or worsened by such ß-blockers. CASES: Case 1 is a 38-year-old man with worsening of tremor in both upper extremities after the introduction of pindolol as an adjunct treatment for severe depression. The tremor improved 1 month after discontinuing this medication. Case 2 is a 77-year-old woman with new bilateral hand tremor after receiving labetalol for the management of hypertension during a hospital admission. Tremor markedly attenuated after eliminating labetalol. CONCLUSION: ß-Blockers with partial agonist activity can induce or exacerbate tremor.