Variant recurrence confirms the existence of a FBXO31-related spastic-dystonic cerebral palsy syndrome.
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ABSTRACT:
SUBMITTER: Dzinovic I
PROVIDER: S-EPMC8045898 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo examine the feasibility and practicality of whole body vibration therapy for individuals with dystonic or spastic dystonic cerebral palsy.DesignPilot study.SubjectsChildren and adults with dystonic or spastic dystonic cerebral palsy.MethodsStudy participants received total body vibration therapy when standing still on a vibration platform for 3 bouts, duration 3-min, of vibration (20 Hz, 2 mm amplitude), 4 days per week for 4 weeks in addition to their usual therapy. All participants were assessed at baseline and completion of the study using the Gross Motor Function Measure Item Set, Timed Up and Go test, Barry-Albright Dystonia Scale, Edinburgh Visual Gait Score, and Pediatric Evaluation of Disability Inventory.ResultsTen participants (mean age 18.60 years (standard deviation (SD) 14.68); 9 males, Gross Motor Function Classification System level II-IV) completed the study with more than 90% attendance rate. All participants tolerated the protocol with no adverse events.ConclusionThe vibration treatment protocol was feasible and safe for all participants. With no significant differences found in all the outcome measures, future studies with more rigorous study designs are required before this intervention is recommended for this population group.
| S-EPMC8008730 | biostudies-literature
Project description:Glutaric aciduria type 1 (GA1) is an inherited inborn error of metabolism caused by a deficiency of the enzyme glutaryl Co-A dehydrogenase (GCDH). Here, we report a 14-month-old Saudi boy with GA1 who presented with severe dystonia and was mis-diagnosed as cerebral palsy (CP). He presented to our institute with encephalopathy following an episode of gastroenteritis. His physical examination showed dystonia and spastic quadriplegia. His investigations revealed elevated both urinary 3-hydroxy glutaric acid, and serum glutarylcarnitine. The DNA analysis confirmed homozygosity for a mutation in the GCDH-coding gene (c.482G greater than A; p.R161Q). This case alerts pediatricians to consider GA1 as a differential diagnosis of children presenting with dystonic CP.
| S-EPMC4673376 | biostudies-literature
Project description:Choreoathetoid movements are quite common in cerebral palsy (CP). This is the first report of a patient with choreoathetoid CP who was successfully treated with carbamazepine. Therefore, clinicians should try carbamazepine for involuntary movements in CP patients before pursuing other procudures.
| S-EPMC6183257 | biostudies-literature
Project description:IntroductionSpastic diplegia presenting in infancy is common to both cerebral palsy (CP) and hereditary spastic paraplegia (HSP). We report the clinical and genetic features of a cohort of Alberta patients with a diagnosis of HSP, who were initially diagnosed with CP.MethodsFourteen patients with an initial diagnosis of CP were identified from an Alberta registry of HSP patients via chart review. Whole exome sequencing (WES) was performed to identify genetic causes.ResultsFrom 90 families in the database, individuals in 29 families had a pediatric presentation of spasticity, with 20 presenting under 3 years of age. Individuals from 14 families had received an initial diagnosis of CP and correct diagnosis was made after neurogenetic assessment due to symptom progression. All had early onset (<3 years) of symptoms. WES identified pathogenic or likely pathogenic mutations in nine cases involving six genes: ATL1, PLP1, PNPLA6, SACS, SPAST, and SYNE1. In five families, WES did not reveal a genetic etiology but progression of symptoms and positive family history suggests HSP is the most likely diagnosis.ConclusionIn our cohort, 70% of HSP children presenting with spasticity under 3 years had been misdiagnosed with CP. In a young child presenting with spastic diplegia without clear history of prematurity, intrauterine growth restriction, infection or vascular insult, it is important to consider HSP. Accurate diagnosis has implications for prognosis, management, and recurrence risk.
| S-EPMC8592889 | biostudies-literature
Project description:AimTo compare anterior and posterior standing balance reactions, as measured by single-stepping thresholds, in children with and without spastic cerebral palsy (CP).MethodSeventeen ambulatory children with spastic CP (eight males, nine females) and 28 typically developing children (13 males, 15 females; age range 5-12y, mean [SD] 9y 2mo [2y 3mo]), were included in this cross-sectional, observational study. Balance reaction skill was quantified as anterior and posterior single-stepping thresholds, or the treadmill-induced perturbations that consistently elicited a step in that direction. In order to understand the underlying mechanisms of between-group differences in stepping thresholds, dynamic stability was quantified using the minimum margin of stability. Ankle muscle activation latency, magnitude, and co-contraction were assessed with surface electromyography.ResultsWe observed an age and group interaction for anterior thresholds (p=0.001, partial η2 =0.24). At older (≈11y; p<0.001, partial η2 =0.48), but not younger (≈7y; p=0.33, partial η2 =0.02) ages, typically developing children had larger anterior thresholds than those with CP. In response to near-threshold anterior perturbations, older typically developing children recovered from more instability than their peers with CP (p=0.004, partial η2 =0.18). Older children had no between-group differences in ankle muscle activity. No between-group differences were observed in posterior thresholds.InterpretationThe effects of CP on balance reactions are age- and direction-specific. Older typically developing children are more able or willing to withhold a step when unstable.What this paper addsChildren with spastic cerebral palsy have age- and direction-specific balance-reaction impairments. Lower anterior stepping thresholds were observed in older, but not younger children. Older typically developing children withheld a forward step at higher levels of instability. No between-group differences were seen in posterior stepping thresholds.
| S-EPMC7916524 | biostudies-literature
Project description:Our study was designed to pinpoint the chief molecule playing the specific and critical role in the neuroinflammation in spastic CP, which may provide promising target for diagonosis and treatment of spastic CP. To further our exploration, our future study will focus on the molecular mechanism of how TNAP regulates the pro- inflammatory factors related to CP neuroinflammation
2022-08-26 | PXD034911 | Pride
Project description:Hereditary spastic paraplegia (HSP) is a neurological, genetic disorder that predominantly presents with lower limb spasticity and muscle weakness. Pediatric pure HSP types with infancy or childhood symptom onset resemble in clinical presentation to children with bilateral spastic cerebral palsy (SCP). Hence, treatment approaches in these patient groups are analogous. Altered muscle characteristics, including reduced medial gastrocnemius (MG) muscle growth and hyperreflexia have been quantified in children with SCP, using 3D-freehand ultrasound (3DfUS) and instrumented assessments of hyperreflexia, respectively. However, these muscle data have not yet been studied in children with HSP. Therefore, we aimed to explore these MG muscle characteristics in HSP and to test the hypothesis that these data differ from those of children with SCP and typically developing (TD) children. A total of 41 children were retrospectively enrolled including (1) nine children with HSP (ages of 9-17 years with gross motor function levels I and II), (2) 17 age-and severity-matched SCP children, and (3) 15 age-matched typically developing children (TD). Clinically, children with HSP showed significantly increased presence and severity of ankle clonus compared with SCP (p = 0.009). Compared with TD, both HSP and SCP had significantly smaller MG muscle volume normalized to body mass (p ≤ 0.001). Hyperreflexia did not significantly differ between the HSP and SCP group. In addition to the observed pathological muscle activity for both the low-velocity and the change in high-velocity and low-velocity stretches in the two groups, children with HSP tended to present higher muscle activity in response to increased stretch velocity compared with those with SCP. This exploratory study is the first to reveal MG muscle volume deficits in children with HSP. Moreover, high-velocity-dependent hyperreflexia and ankle clonus is observed in children with HSP. Instrumented impairment assessments suggested similar altered MG muscle characteristics in pure HSP type with pediatric onset compared to bilateral SCP. This finding needs to be confirmed in larger sample sizes. Hence, the study results might indicate analogous treatment approaches in these two patient groups.
| S-EPMC7952873 | biostudies-literature
Project description:A subset of individuals diagnosed with cerebral palsy will have an underlying genetic diagnosis. Previously, a missense variant in GAD1 was described as a candidate mutation in a single family diagnosed with autosomal recessive spastic cerebral palsy-1 (CPSQ1; OMIM 603513). Following the ascertainment of a further branch of the CPSQ1 kindred, we found that the previously reported GAD1 variant did not segregate with the neurological disease phenotype in the recently ascertained branch of the kindred. Following genetic linkage studies to map autozygous regions and whole-exome sequencing, a missense variant (c.527 T > C; p. Leu176Pro, rs773333490) in the HPDL gene was detected and found to segregate with disease status in both branches of the kindred. HPDL encodes a 371-amino acid protein (4-Hydroxyphenylpyruvate Dioxygenase Like) that localizes to mitochondria but whose function is uncertain. Recently, biallelic loss of function variants and missense substitution-causing variants in HPDL were reported to cause a childhood onset progressive spastic movement disorder with a variable presentation. These findings suggest that HPDL-related neurological disease may mimic spastic cerebral palsy and that GAD1 should not be included in diagnostic gene panels for inherited cerebral palsy.
| S-EPMC7892364 | biostudies-literature
Project description:Cerebral palsy (CP) has long been investigated to be associated with a range of motor and cognitive dysfunction. As the two most common CP subtypes, spastic cerebral palsy (SCP) and dyskinetic cerebral palsy (DCP) may share common and distinct elements in their pathophysiology. However, the common and distinct dysfunctional characteristics between SCP and DCP on the brain network level are less known. This study aims to detect the alteration of brain functional connectivity in children with SCP and DCP based on resting-state functional MRI (fMRI). Resting-state networks (RSNs) were established based on the independent component analysis (ICA), and the functional network connectivity (FNC) was performed on the fMRI data from 16 DCP, 18 bilateral SCP, and 18 healthy children. Compared with healthy controls, altered functional connectivity within the cerebellum network, sensorimotor network (SMN), left frontoparietal network (LFPN), and salience network (SN) were found in DCP and SCP groups. Furthermore, the disconnections of the FNC consistently focused on the visual pathway; covariance of the default mode network (DMN) with other networks was observed both in DCP and SCP groups, while the DCP group had a distinct connectivity abnormality in motor pathway and self-referential processing-related connections. Correlations between the functional disconnection and the motor-related clinical measurement in children with CP were also found. These findings indicate functional connectivity impairment and altered integration widely exist in children with CP, suggesting that the abnormal functional connectivity is a pathophysiological mechanism of motor and cognitive dysfunction of CP.
| S-EPMC6114065 | biostudies-literature
Project description:AimTo determine the prevalence of dystonia in individuals with periventricular leukomalacia (PVL) and spastic cerebral palsy (CP), but without basal ganglia and thalamic injury (BGTI) on brain magnetic resonance imaging (MRI).MethodThis was a retrospective study of individuals with spastic CP and PVL on MRI evaluated between 2005 and 2018 in a CP center. Individuals with non-PVL brain lesions on MRI, including BGTI, were excluded. Dystonia was assessed via blinded review of neurological exam videos by pediatric movement disorders specialists.ResultsEighty-five participants (45 males, 40 females; mean age at videotaping 12 years [standard deviation 5 years 6 months], range 4-26 years) met inclusion and exclusion criteria. Of these participants, 50 (59%) displayed dystonia in their exam videos. The most common locations of dystonia were the fingers and hip adductors. The prevalence of dystonia was unaffected by the gestational age or severity of PVL, and was affected by Gross Motor Function Classification System level.InterpretationDystonia is common in individuals with spastic CP and PVL, even without BGTI on MRI. Our findings suggest vigilance for dystonia in individuals with spastic CP should remain high, even without MRI evidence of BGTI.What this paper addsIndividuals with spastic cerebral palsy and isolated periventricular leukomalacia on magnetic resonance imaging commonly display dystonia. Common sites of dystonia are in the fingers and hip adductors.
| S-EPMC10392705 | biostudies-literature