Citations

Background and purposeTo describe speech, neurological and imaging characteristics of a series of patients presenting with progressive spastic dysarthria as the first and predominant sign of a presumed neurodegenerative disease.MethodsParticipants were 25 patients with spastic dysarthria as the only or predominant speech disorder. Clinical features, pattern of MRI volume loss on voxel‐based morphometry and pattern of hypometabolism on F18‐fluorodeoxyglucose positron emission tomography (FDG‐PET) scan are described.ResultsAll patients demonstrated speech characteristics consistent with spastic dysarthria, including strained voice quality, slow speaking rate, monopitch and monoloudness, and slow and regular speech alternating motion rates. Eight patients did not have additional neurological findings on examination. Pseudobulbar affect, upper motor neuron pattern limb weakness, spasticity, Hoffman sign and positive Babinski reflexes were noted in some of the remaining patients. Twenty‐three patients had electromyographic assessment and none had diffuse motor neuron disease or met El Escorial criteria for amyotrophic lateral sclerosis. Voxel‐based morphometry revealed striking bilateral white matter volume loss affecting the motor cortex (BA 4), including the frontoparietal operculum (BA 43) with extension into the middle cerebral peduncle. FDG‐PET showed subtle hypometabolism affecting the premotor and motor cortices in some patients, particularly in those who had a disease duration longer than 2 years.ConclusionsA neurodegenerative disorder that begins focally with spastic dysarthria due to involvement of the motor and premotor cortex and descending corticospinal and corticobulbar pathways is characterized. The descriptive label ‘progressive spastic dysarthria’ to best capture the dominant presenting feature of the syndrome is proposed.

ABSTRACTIntroduction: Repetitive discharges may be recorded during nerve conduction studies (NCS) or during needle electromyography in a muscle at rest. Repetitive discharges that occur during voluntary activation and are time‐locked to voluntary motor unit potentials (MUP) have not been described. Methods: Retrospective review of motor unit potential induced repetitive discharges (MIRDs) identified in the EMG laboratory. Characteristics of each MIRD, patient demographics, other EMG findings in the same muscle, and electrophysiological diagnosis were analyzed. Results: MIRDs were observed in 15 patients. The morphology and number of spikes and duration of MIRDs varied. The discharges fired at rates of 50–200 Hz. All but 2 patients had EMG findings of a chronic neurogenic disorder. Conclusions: MIRDs are rare iterative discharges time‐locked to a voluntary MUP. The pathophysiology of MIRDs is unclear, but their presence may indicate a chronic neurogenic process. Muscle Nerve 48: 977–979, 2013

Objective To identify factors associated with triptan discontinuation among migraine patients. Background It is unclear why many migraine patients who are prescribed triptans discontinue this treatment. This study investigated correlates of triptan discontinuation with a focus on potentially modifiable factors to improve compliance. Methods This multicenter cross‐sectional survey (n = 276) was performed at US tertiary care headache clinics. Headache fellows who were members of the American Headache Society Headache Fellows Research Consortium recruited episodic and chronic migraine patients who were current triptan users (use within prior 3 months and for ≥1 year) or past triptan users (no use within 6 months; prior use within 2 years). Univariate analyses were first completed to compare current triptan users to past users for: migraine characteristics, other migraine treatments, triptan education, triptan efficacy, triptan side effects, type of prescribing provider, Migraine Disability Assessment ( MIDAS ) scores and Beck Depression Inventory ( BDI ) scores. Then, a multivariable logistic regression model was selected from all possible combinations of predictor variables to determine the factors that best correlated with triptan discontinuation. Results Compared with those still using triptans (n = 207), those who had discontinued use (n = 69) had higher rates of medication overuse (30 vs 18%, P = .04) and were more likely to have ever used opioids for migraine treatment (57 vs 38%, P = .006) as well as higher MIDAS (mean 63 vs 37, P = .001) and BDI scores (mean 10.4 vs 7.4, P = .009). Compared with discontinued users, current triptan users were more likely to have had their triptan prescribed by a specialist (neurologist, headache specialist, or pain specialist) (74 vs 54%, P = .002) and were more likely to report headache resolution (53 vs 14%, P < .001) or a reduction in pain intensity (71 vs 28%, P < .001) most of the time from their triptan. On a 1‐5 scale (1 = disagree, 5 = agree), triptan users felt they had more: control over their migraine attacks (2.9 vs 2.1), confidence in their prescribing provider (4.5 vs 4.0), and were more educated about triptan use (4.2 vs 3.7) compared with triptan discontinuers ( P < .001 for all comparisons). Although both current and prior users reported similar rates of side effects (48 vs 43%, P = .44), of those who discontinued use, the main reasons were for lack of effect (44%) and side effects (29%). Our multivariable modeling revealed that the strongest correlate of triptan discontinuation was lack of efficacy (odds ratio = 17, 95% confidence interval [8.8, 33.0]). Other factors associated with discontinuation included MIDAS > 24 (2.6, [1.5, 4.6]), BDI >4 (2.5, [1.4, 4.5]), and a history of ever using opioids for migraine therapy (2.2, [1.3, 3.8]). Having a triptan prescribed by a specialist and using at least 1 other abortive medication with the triptan were associated with a decreased likelihood of triptan discontinuation (0.41, [0.2‐0.7] and 0.44 [0.3, 0.8], respectively). Conclusions As expected, discontinuation was most correlated with lack of efficacy, but other important factors associated with those who had discontinued use included greater migraine‐related disability, depression, and the use of opioids for migraine attacks. Compared with patients who had discontinued triptans, current triptan users felt more: educated about their triptan, control over their migraine attacks, and confidence in their prescribing provider. Current triptan users had their triptan prescribed by a specialist and used other abortive medications with their triptan more often compared with patients who had discontinued triptans. Given the cross‐sectional nature of this study, we cannot determine if these factors contributed to triptan discontinuation or reflect the impact of such discontinuation. Interventions that address modifiable risk factors for triptan discontinuation may decrease the likelihood of triptan discontinuation and thus improve overall migraine control. Because lack of efficacy was most strongly associated with triptan discontinuation, future research should determine why triptans are effective for some patients but not others.

Key PointsPhenotypic and genotypic profiling of MDM2 in DLBCL. MDM2 as a negative regulator of p53 tumor suppressor function.

Purpose With improved patient care, better diagnosis, and more treatment options after tumor recurrence, outcomes after fluorouracil (FU) -based treatment are expected to have improved over time in early-stage colon cancer. Data from 18,449 patients enrolled onto 21 phase III trials conducted from 1978 to 2002 were evaluated for potential differences in time to recurrence (TTR), time from recurrence to death (TRD), and overall survival (OS) with regard to FU-based adjuvant regimens. Methods Trials were predefined as old versus newer era using initial accrual before or after 1995. Outcomes were compared between patients enrolled onto old- or newer-era trials, stratified by stage. Results Within the first 3 years, recurrence rates were lower in newer- versus old-era trials for patients with stage II disease, with no differences among those with stage III disease. Both TRD and OS were significantly longer in newer-era trials overall and within each stage. The lymph node (LN) ratio (ie, number of positive nodes divided by total nodes harvested) in those with stage III disease declined over time. TTR improved slightly, with larger number of LNs examined in both stages. Conclusion Improved TRD in newer trials supports the premise that more aggressive intervention (oxaliplatin- and irinotecan-based chemotherapy and/or surgery for recurrent disease) improves OS for patients previously treated in the adjuvant setting. Lower recurrence rates with identical treatments in those with stage II disease enrolled onto newer-era trials reflect stage migration over time, calling into question historical data related to the benefit of FU-based adjuvant therapy in such patients.