Adult diagnosis of congenital serine biosynthesis defect: A treatable cause of progressive neuropathy.

A woman with ichthyosis, contractures, and progressive neuropathy represents the first case of phosphoserine aminotransferase deficiency diagnosed and treated in an adult. She has novel compound heterozygous mutations in the gene PSAT1. Treatment with high dose oral L-serine completely resolved the ichthyosis. Consideration of this diagnosis is important because early treatment with L-serine repletion can halt progression of neurodegeneration and potentially improve neurological disabilities. As exome sequencing becomes more widely implemented in the diagnostic evaluation of progressive neurodegenerative phenotypes, adult neurologists and geneticists will increasingly encounter later onset manifestations of inborn errors of metabolism classically considered in infancy and early childhood.

Association of Miglustat With Swallowing Outcomes in Niemann-Pick Disease, Type C1.

Importance: Niemann-Pick disease, type C1 (NPC1) is a progressive neurovisceral disease with no US Food and Drug Administration-approved therapy. Miglustat, a drug used off-label in the United States for the treatment of NPC1, appears to stabilize neurologic disease progression. Several prospective trials suggest that miglustat stabilizes oropharyngeal swallowing function; however, its effect on dysphagia and aspiration risk has not been demonstrated instrumentally. Objective: To determine if miglustat therapy is associated with stabilized swallowing dysfunction in individuals with NPC1. Design, Setting, and Participants: Patients with confirmed NPC1 diagnoses were evaluated in a single-center cohort study of NPC1 from April 1997 to November 2019. Longitudinal data from individuals with neurologic disease onset prior to age 15 years were analyzed. The study population was divided into those with neurologic disease onset in early childhood (age <6 years) and late childhood (age ≥6 years and <15 years). Analysis began September 2019. Exposures: Oral miglustat at baseline and at follow-up. Main Outcomes and Measures: Oropharyngeal swallowing function was assessed with videofluoroscopic swallowing studies. Overall swallowing ability and aspiration risk were evaluated using the American Speech-Language-Hearing Association National Outcome Measurement System swallowing domain and an adapted Rosenbek aspiration-penetration scale, respectively. Results: Overall, 50 participants were evaluated at baseline (median [interquartile range] age, 9.4 [3.4-16.4] years; 26 [52%] female). The median (interquartile range) duration of follow-up was 3.0 (1.1-4.4) years. Miglustat use was associated with decreased odds of worse American Speech-Language-Hearing Association National Outcome Measurement System swallowing domain outcomes in all 3 subsets (overall: odds ratio [OR], 0.09 [95% CI, 0.02-0.36); P < .001; early childhood: OR, 0.17 [95% CI, 0.04-0.67]; P = .01; late childhood: OR, 0.05 [95% CI, 0.01-0.29]; P = .001). Miglustat use was associated with decreased odds of worse Rosenbek aspiration-penetration scale outcomes in the overall cohort (OR, 0.28 [95% CI, 0.08-0.95]; P = .04) but not in each subgroup (early childhood: OR, 0.27 [95% CI, 0.06-1.22]; P = .09; late childhood: OR, 0.38 [95% CI, 0.06-2.33]; P = .29). Conclusions and Relevance: These data suggest that miglustat use is associated with stabilized swallowing function and reduced aspiration risk in NPC1, thus supporting its use in this population. In addition, these data demonstrate that a quantification of swallowing dysfunction can be used as a clinically relevant, functional outcome measure in future therapeutic trials in NPC1.

Verb and noun deficits in stroke-induced and primary progressive aphasia: The Northwestern Naming Battery().

BACKGROUND: Word class naming deficits are commonly seen in aphasia resulting from stroke (StrAph) and primary progressive aphasia (PPA), with differential production of nouns (objects) and verbs (actions) found based on StrAph type or PPA variant for some individuals. Studies to date, however, have not compared word class naming (or comprehension) ability in the two aphasic disorders. In addition, there are no available measures for testing word class deficits, which control for important psycholinguistic variables across language domains. This study examined noun and verb production and comprehension in individuals with StrAph and PPA using a new test, the Northwestern Naming Battery (NNB; Thompson & Weintraub, experimental version), developed explicitly for this purpose. In addition, we tested verb type effects, based on verb argument structure characteristics, which also is addressed by the NNB. METHOD: Fifty-two participants with StrAph (33 agrammatic, Broca's (StrAg); 19 anomic (StrAn)) and 28 PPA (10 agrammatic (PPA-G); 14 logopenic (PPA-L); 4 semantic (PPA-S)) were included in the study. Nouns and verbs were tested in the Confrontation Naming and Auditory Comprehension subtests of the NNB, with scores used to compute noun to verb ratios as well as performance by verb type. Performance patterns within and across StrAph and PPA groups were then examined. The external validity of the NNB also was tested by comparing (a) NNB Noun Naming scores to the Boston Naming Test (BNT; Kaplan, Goodglass, & Weintraub, 1983) and Western Aphasia Battery (WAB-R, Kertesz, 2007) Noun Naming subtest scores, (b) NNB Verb Naming scores to the Boston Diagnostic Aphasia Examination (BDAE; Goodglass, Kaplan & Barresi, 2001) Action Naming score (for StrAph participants only), and (c) NNB Comprehension subtest scores to WAB-R Auditory Comprehension subtest scores. OUTCOMES AND RESULTS: Both agrammatic (StrAg and PPA-G) groups showed significantly greater difficulty producing verbs compared to nouns, but no comprehension impairment for either word class. Whereas, three of the four PPA-S participants showed poorer noun compared to verb production, as well as comprehension. However, neither the StrAn or PPA-L participants showed significant differences between the two word classes in production or comprehension. In addition, similar to the agrammatic participants, the StrAn participants showed a significant transitivity effect, producing intransitive (one-argument) verbs with greater accuracy than transitive (two- and three-argument) verbs. However, no transitivity effects were found for the PPA-L or PPA-S participants. There were significant correlations between NNB scores and all external validation measures. CONCLUSIONS: These data indicate that the NNB is sensitive to word class deficits in stroke and neurodegenerative aphasia. This is important both clinically for treatment planning and theoretically to inform both psycholinguistic and neural models of language processing.

The effects of compression garments on recovery of muscle performance following high-intensity sprint and plyometric exercise.

This study compared the effects of compression garments on recovery of evoked and voluntary performance following fatiguing exercise. Eleven participants performed 2 sessions separated by 7 days, with and without lower-body compression garments during and 24h post-exercise. Participants performed a 10-min exercise protocol of a 20-m sprint and 10 plyometric bounds every minute. Before, following, 2h and 24h post-exercise, evoked twitch properties of the knee extensors, peak concentric knee extension and flexion force were assessed, with blood samples drawn to measure lactate [La(-)], pH, creatine kinase (CK), aspartate transaminase (AST) and c-reactive protein (C-RP). Heart rate, exertion (RPE) and muscle soreness (MS) measures were obtained pre- and post-exercise. No differences (P=0.50-0.80) and small effect sizes (d<0.3) were present for 20-m sprint (3.59+/-0.22 vs. 3.59+/-0.18s) or bounding performance (17.13+/-1.4 vs. 17.21+/-1.7 m) in garment and control conditions. The decline and recovery in concentric force were not different (P=0.40) between conditions. Full recovery of voluntary performance was observed 2h post-exercise, however, evoked twitch properties remained suppressed 2h post-exercise in both conditions. No differences (P=0.40-0.80, d<0.3) were present between conditions for heart rate, RPE, [La(-)], pH, CK or C-RP. However, 24h post-exercise a smaller change (P=0.08; d=2.5) in AST (23.1+/-3.1 vs. 26.0+/-4.0) and reduced (P=0.01; d=1.1) MS (2.8+/-1.2 vs. 4.5+/-1.4) were present in the garments. In conclusion the effects of compression garments on voluntary performance and recovery were minimal; however, reduced levels of perceived MS were reported following recovery in the garments.

The effects of recovery interventions on consecutive days of intermittent sprint exercise.

The purpose of this study was to compare four recovery interventions following simulated team sport, intermittent-sprint exercise on consecutive days. Ten female netball players performed four randomized sessions of a simulated netball exercise circuit on consecutive days. Each condition consisted of two identical sessions (Session 1 and 2), with the recovery intervention implemented at the completion of Session 1. Participants performed all interventions involving: passive recovery, active recovery (ACT), cold water immersion (CWI) and contrast water therapy (C(T)WT). No significant differences (p > 0.05) were evident between conditions for exercise performance (vertical jump, 20-m sprint, 10-m sprint, total circuit time) during Session 2. Effect size data indicated trends for an ameliorated decline in 5 x 20-m sprints and vertical jump for C(T)WT and CWI, respectively. C(T)WT demonstrated a significant reduction (p = 0.04) in lactate post-intervention compared to ACT recovery. Further, ACT recovery resulted in a significantly elevated (p < 0.01) heart rate compared to all other conditions postintervention and demonstrated significantly higher (p < 0.01) rating of perceived exertion postintervention and muscle soreness pre-exercise Session 2. It is likely that while interventions may be applicable to team sport practices, the 24-hour recovery period between exercise bouts was sufficient to allow performance to be maintained, regardless of recovery interventions.

Recovery of voluntary and evoked muscle performance following intermittent-sprint exercise in the heat.

PURPOSE: This study investigated the effects of hot conditions on the acute recovery of voluntary and evoked muscle performance and physiological responses following intermittent exercise. METHODS: Seven youth male and six female team-sport athletes performed two sessions separated by 7 d, involving a 30-min exercise protocol and 60-min passive recovery in either 22 degrees C or 33 degrees C and 40% relative humidity. The exercise protocol involved a 20-s maximal sprint every 5 min, separated by constant-intensity exercise at 100 W on a cycle ergometer. Maximal voluntary contraction (MVC) and a resting evoked twitch (Pf) of the right knee extensors were assessed before and immediately following exercise and again 15, 30, and 60 min postexercise, and capillary blood was obtained at the same time points to measure lactate, pH, and HCO3. During and following exercise, core temperature, heart rate and rating of perceived exertion (RPE) were also measured. RESULTS: No differences (P=0.73 to 0.95) in peak power during repeated sprints were present between conditions. Postexercise MVC was reduced (P<.05) in both conditions and a moderate effect size (d=0.60) indicated a slower percentage MVC recovered by 60 min in the heat (83+/-10 vs 74+/-11% recovered). Both heart rate and core temperature were significantly higher (P<.05) during recovery in the heat. Capillary blood values did not differ between conditions at any time point, whereas sessional RPE was higher 60 min postexercise in the heat. CONCLUSIONS: The current data suggests that passive recovery in warm temperatures not only delays cardiovascular and thermal recovery, but may also slow the recovery of MVC and RPE.