Kearns-Sayre syndrome (KSS) is a rare mitochondrial disease associated to a widespread cerebral leukodystrophy. MRI shows a typical centripetal pattern where U-fibers are mainly affected with a ...relative spare of periventricular white matter. Recently, different patterns of spinal cord involvement have been described in KSS. Here we report 4 new cases with typical cerebral leukodystrophy associated with spinal cord lesions. A pattern characterized by abnormal signal intensity in the H gray matter and posterior columns was found in 2 patients, while the remaining 2 presented a peculiar involvement of the spinal trigeminal nuclei at the junction of low medulla and cervical cord. MRI spinal cord involvement in KSS is probably an underestimated finding and should be evaluated in the diagnostic work up of these patients.
The terms Pediatric Autoimmune Neuropsychiatric disorders associated with streptococcal infections (PANDAS), Pediatric acute-onset neuropsychiatric Syndrome (PANS), and Childhood Acute ...Neuropsychiatric Symptoms (CANS) have been used to describe certain acute onset neuropsychiatric pediatric disorders. This clinical characteristic was unusually abrupt onset of obsessive compulsive symptoms and/or severe eating restrictions and concomitant cognitive, behavioral or neurological symptoms. Because the CANS/PANS criteria define a broad spectrum of neuropsychiatric conditions, the syndrome is presumed to result from a variety of disease mechanisms and to have multiple etiologies, ranging from postinfectious autoimmune and neuroinflammatory disorders to toxic, endocrine or metabolic disorders. We suggest a diagnostic flow-chart in case of acute onset neuropsychiatric syndrome to better define diagnostic criteria, identify possible subtypes and delineate treatment.
•Definition of acute-onset neuropsychiatric symptoms triggered by infectious agents.•Clinical characteristic of CANS and PANS are discussed.•Diagnostic criteria and limitations of each one are reviewed.
Cerebral palsy (CP) is a heterogeneous group of syndromes that cause a non-progressive disorder of early onset, with abnormal control of movement and posture. Various aetiologies can cause the CP ...clinical spectrum, but all have a disruption of motor control in common. CP can be divided into four major types based on the motor disability: predominant spastic, dyskinetic, ataxic and mixed form. Dyskinetic CP (DCP) is the most common cause of acquired dystonia in children. The treatment of DCP is challenging because most individuals have mixed degrees of chorea, athetosis and dystonia. Pharmacological treatment is often unsatisfactory. Functional neurosurgery, in particular deep brain stimulation targeting the basal ganglia or the cerebellum, is emerging as a promising therapeutic approach in selected patients with DCP. We evaluated herein the effects of DBS on patients with DCP in a review of published patient data in the largest available studies.
•Cerebral palsy is a complex condition frequently dominated by dystonic features.•Bilateral DBS of the GPi has been associated with a variable improvement of dystonia in cerebral palsy (range 1–50%).•The appropriate selection of patients with prominent dystonia is of key importance for the therapeutic success of DBS.
Mitochondrial membrane Protein-Associated Neurodegeneration (MPAN) is a lethal neurodegenerative disorder caused by mutations in the human gene C19orf12. The molecular mechanisms underlying the ...disorder are still unclear, and no established therapy is available. Here, we describe the generation and characterization of two human induced pluripotent stem cell (iPSC) lines derived from skin fibroblasts of two MPAN patients carrying homozygous recessive mutations in C19orf12. These iPSC lines represent a useful resource for future investigations on the pathology of MPAN, as well as for the development of successful treatments.
Dystonia is a clinically and genetically heterogeneous movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements and/or postures. ...Heterozygous variants in lysine methyltransferase 2B (KMT2B), encoding a histone H3 methyltransferase, have been associated with a childhood-onset, progressive and complex form of dystonia (dystonia 28, DYT28). Since 2016, more than one hundred rare KMT2B variants have been reported, including frameshift, nonsense, splice site, missense and other in-frame changes, many having an uncertain clinical impact.
We characterize the genome-wide peripheral blood DNA methylation profiles of a cohort of 18 patients with pathogenic and unclassified KMT2B variants. We resolve the "episignature" associated with KMT2B haploinsufficiency, proving that this approach is robust in diagnosing clinically unsolved cases, properly classifying them with respect to other partially overlapping dystonic phenotypes, other rare neurodevelopmental disorders and healthy controls. Notably, defective KMT2B function in DYT28 causes a non-random DNA hypermethylation across the genome, selectively involving promoters and other regulatory regions positively controlling gene expression.
We demonstrate a distinctive DNA hypermethylation pattern associated with DYT28, provide an epigenetic signature for this disorder enabling accurate diagnosis and reclassification of ambiguous genetic findings and suggest potential therapeutic approaches.
Paroxysmal exercise-induced neurological symptoms (PENS) encompass a wide spectrum of clinical phenomena commonly presenting during childhood and characteristically elicited by physical exercise. ...Interestingly, few shared pathogenetic mechanisms have been identified beyond the well-known entity of paroxysmal exercise-induced dyskinesia, PENS could be part of more complex phenotypes including neuromuscular, neurodegenerative, and neurometabolic disease, epilepsies, and psychogenetic disorders. The wide and partially overlapping phenotypes and the genetic heterogeneity make the differential diagnosis frequently difficult and delayed; however, since some of these disorders may be treatable, a prompt diagnosis is mandatory. Therefore, an accurate characterization of these symptoms is pivotal for orienting more targeted biochemical, radiological, neurophysiological, and genetic investigations and finally treatment. In this article, we review the clinical, genetic, pathophysiologic, and therapeutic landscape of paroxysmal exercise induced neurological symptoms, focusing on phenomenology and differential diagnosis.
This observational study aims to characterize, from a socio-demographic and psychopathological perspective, a sample of children with Functional Neurological Disorders (FND). Thirteen paediatric ...patients (below 18 years old) with FND and their parents completed a battery of anamnestic and neuropsychological tests, assessing socio-demographic status, cognitive level, behavioural and emotional issues, depression, anxiety, alexithymic traits and dissociative symptoms. Five patients presented movement disorders (tremor, myoclonus and gait disorder), three patients psychogenic non-epileptic seizures and five patients sensitivity disturbances (pain, anaesthesia and paraesthesia). Cognitive profile was normal in 11 patients; academic performance was good in nine patients, but three had a diagnosis of Specific Learning Difficulty or Attention Deficit Hyperactivity Disorder. Precipitating events occurred in 11 patients. At the self-report questionnaires, mean scores close to the clinical cut off were documented with respect to affective and somatic problems. At the parent-report questionnaires, clinically significant mean scores were observed in the subscales assessing anxious–depressive symptoms and somatic complaints. We speculate that paediatric FND patients, although acknowledging the relevance of somatic symptoms, have difficulties in recognizing internal emotional states (that, instead, are easily recognized by their parents). The case of one FND patient was described. These preliminary data might help identifying different clinical phenotypes of paediatric FND.
This study is aimed at better understanding the role of a wearable and silent ElectroMyoGraphy-based biofeedback on motor learning in children and adolescents with primary and secondary dystonia.
A ...crossover study with a wash-out period of at least 1 week was designed; the device provides the patient with a vibration proportional to the activation of an impaired target muscle. The protocol consisted of two 5-day blocks during which subjects were trained and tested on a figure-8 writing task: their performances (at different levels of difficulty) were evaluated in terms of both kinematics and muscular activations on day 1 and day 5, while the other 3 days were purely used as training sessions. The training was performed with and without using the biofeedback device: the week of use was randomized. Data were collected on 14 subjects with primary and secondary (acquired) dystonia (age: 6-19 years).
Results comparing kinematic-based and EMG-based outcome measures pre- and post-training showed learning due to practice for both subjects with primary and secondary dystonia. On top of said learning, an improvement in terms of inter-joint coordination and muscular pattern functionality was recorded only for secondary dystonia subjects, when trained with the aid of the EMG-based biofeedback device.
Our results support the hypothesis that children and adolescents with primary dystonia in which there is intact sensory processing do not benefit from feedback augmentation, whereas children with secondary dystonia, in which sensory deficits are often present, exhibit a higher learning capacity when augmented movement-related sensory information is provided. This study represents a fundamental investigation to address the scarcity of noninvasive therapeutic interventions for young subjects with dystonia.
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