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PURPOSE: In this study, patients with epilepsy with eyelid myoclonia (E-EM) were evaluated according to their EEG findings, seizure outcomes, and their consistency with the final ictal EEG findings. We also investigated the possible prognostic factors. METHODS: Patients with E-EM and at least two years of follow-up in our clinic were included in the study. We analyzed the presence of eyelid myoclonia, absence and myoclonic seizures, and generalized tonic-clonic seizures for the prior two years and then verified with the latest ictal EEG features. Video-EEGs were analyzed according to the background activity, the existence of generalized spike-wave discharge or polyspike-wave complexes, focal spike-wave discharge, photoparoxysmal responses, and fast activity. RESULTS: 21 patients were involved in this study. In six patients, the seizures were undetected on the first EEGs, whereas they were detected on subsequent ones. The seizures were captured on the first EEGs of six patients; however, they disappeared on subsequent ones. Only one patient had seizures detected on every EEG. The consistency of the seizures was variable in eight patients. At the final follow-up, seizures were reported as being under control for more than two years in 12 patients, according to patients and their parents' reports. However, ictal EEG findings were detected in six of these patients. No electroclinical feature was associated with seizure freedom. CONCLUSION: This study provides further evidence that seizure freedom in E-EM patients is overestimated. The patients and their parents may not be aware of the seizures. Therefore, video-EEG monitorization is essential during follow-up.
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Electroencefalografía , Convulsiones , Humanos , Masculino , Femenino , Adulto , Adolescente , Adulto Joven , Niño , Convulsiones/fisiopatología , Convulsiones/diagnóstico , Convulsiones/complicaciones , Mioclonía/fisiopatología , Mioclonía/diagnóstico , Mioclonía/etiología , Persona de Mediana Edad , Párpados/fisiopatología , Grabación en Video , Preescolar , Estudios de Seguimiento , Epilepsias Mioclónicas/fisiopatología , Epilepsias Mioclónicas/complicaciones , Epilepsias Mioclónicas/diagnóstico , Estudios Retrospectivos , Epilepsia/fisiopatología , Epilepsia/complicaciones , Epilepsia/diagnósticoRESUMEN
Introduction: Acyl-CoA binding domain containing 5 (ACBD5) deficiency is a newly defined inborn peroxisomal disorder with only 7 patients reported to date. Herein, we report a patient with ACBD5 deficiency who was diagnosed after a complicated diagnostic process. Case Presentation: A 6-year-old male patient was admitted with complaints of neuromotor regression and visual disturbances. He had spastic paraparesis dominated with axial hypotonic posturing and horizontal nystagmus. His very-long-chain fatty acid levels were within normal ranges with a slightly elevated C26:0/C22:0 ratio. Brain magnetic resonance imaging revealed white matter involvement. Clinical exome sequencing displayed a novel homozygous intronic splice site variant (c.936 + 2T>G) in the ACBD5 (NM_145698.5) gene. Conclusion: With this report, a novel variant in ACBD5 deficiency was described. Macular dystrophy was demonstrated with optical coherence tomography imaging for the first time in the literature in ACBD5 deficiency. In order to contribute to the knowledge about the clinical, biochemical, and genetic spectrum of ACBD5 deficiency, new patients need to be defined.
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BACKGROUND: Pontocerebellar hypoplasia type 10 (PCH10) due to CLP1 gene mutations is characterized by structural brain anomalies, progressive microcephaly, severe intellectual and physical disabilities, and spasticity. In this follow-up study, evolution of phenotypic and neurological characteristics of patients with PCH10 is discussed. METHODS: Phenotype, growth parameters, motor functions, developmental tests, spasticity assessments, functional independence assessments, electroencephalography (EEG), and brain magnetic resonance imaging (MRI) of 10 patients with PCH10 were monitored on separate examinations. Alterations were recorded. RESULTS: Patients were followed-up for an average of 2.83 years. The tone of the upper extremities was significantly higher than that of the lower extremities, according to Modified Ashworth Scale (MAS) values. Sixty percent of patients could sit unsupported; 20% achieved supported sitting initially but lost the ability during follow-up. Absence of grabbing or sitting was observed in 20% of patients. During follow-up, one person achieved supported sitting and one person achieved head holding. Only one patient was able to speak a few words. Cerebellar atrophy (two of 10), pons hypoplasia (four of 10), cortical atrophy (seven of 10), enlarged ventricles (10 of 10), thinning of the corpus callosum (10 of 10), hypomyelination (six of 10), and increased white matter signal intensity (six of 10) were the observed MRI findings. CONCLUSIONS: Progressive cerebral and cerebellar atrophy was demonstrated radiologically for the first time in a PCH10 cohort. It is of crucial importance to identify these patients promptly with the help of dysmorphic findings and spasticity being pronounced in the upper extremities. Furthermore, we note that phenotypic and neurological examination findings tend to change slightly over time.
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Imagen por Resonancia Magnética , Humanos , Masculino , Femenino , Niño , Preescolar , Adolescente , Estudios de Seguimiento , Progresión de la Enfermedad , Lactante , Atrofias Olivopontocerebelosas/patología , Atrofias Olivopontocerebelosas/diagnóstico por imagen , Atrofias Olivopontocerebelosas/fisiopatología , Electroencefalografía , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Fenotipo , Espasticidad Muscular/fisiopatología , Espasticidad Muscular/diagnóstico por imagen , Enfermedades CerebelosasRESUMEN
BACKGROUND: Epileptic encephalopathy with spike-and-wave activation in sleep (EE-SWAS) is a syndrome of childhood, characterized by diffuse or generalized spike-wave activity in electroencephalography during non-rapid eye movement sleep. Neuropeptides have been demonstrated in several studies to function in the sleep-wake cycle and display convulsant and anticonvulsant features. In this study, we aimed to investigate the relationship between EE-SWAS and neuropeptides such as dynorphin, galanin, ghrelin, leptin, melatonin, and orexin. METHODS: This multicenter study was conducted from July 2019 to January 2021. There were three groups: Group 1 contained patients with EE-SWAS. Group 2 consisted of patients with self-limited focal epilepsy of childhood (SeLFE), and group 3 was the control group. Levels of neuropeptides were compared in the sera of these three groups. RESULTS: There were 59 children aged between four and 15 years. Group 1 contained 14 children, group 2 contained 24 children, and group 3 contained 21 children. The level of leptin is higher and the level of melatonin is lower in group 1 than in group 3 (P = 0.01 and P = 0.005, respectively). In group 3, the level of orexin was lower than in both groups 2 and 3 (P = 0.01 and P = 0.01). CONCLUSIONS: These data show that the level of leptin was higher and the level of melatonin was lower in patients with EE-SWAS than in the control group. Furthermore, patients with EE-SWAS had lower orexin levels than both the control group and patients with SeLFE. Further research is required to understand the potential role of these neuropeptides in the pathophysiology of EE-SWAS.
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Epilepsias Parciales , Epilepsia Generalizada , Melatonina , Estado Epiléptico , Niño , Humanos , Preescolar , Adolescente , Orexinas , Leptina , Sueño/fisiología , ElectroencefalografíaRESUMEN
BACKGROUND: Ocrelizumab is a recombinant humanized anti-CD20 monoclonal IgG1, approved by FDA and EMA for adult patients with multiple sclerosis (MS). The data on the efficacy and safety of Ocrelizumab for pediatric MS cases are limited. OBJECTIVE: Here, we describe pediatric relapsing-remitting MS (P-RRMS) cases who were treated with Ocrelizumab as a disease-modifying drug. METHOD: P-RRMS cases who were started Ocrelizumab below 18 years-of-age and followed-up >12 months with Ocrelizumab treatment were included. The primary end-points were annualized relapse rate (ARR) and magnetic resonance imaging (MRI) activity (new/enlarging T2 lesions and new gadolinium (Gd) enhancing lesions). The secondary end-points were the percentage of patients who remain relapse-free and/or free from Gd enhancing lesions, Expanded Disability Status Scale (EDSS) score, and the safety profile of Ocrelizumab. RESULTS: Of 18 P-RRMS cases receiving Ocrelizumab, 10 patients fulfilled the inclusion criteria for our study. The median duration of follow-up under Ocrelizumab was 28,3 months (min: 15 months, max: 46 months). Mean ARR decreased from 2.01 (±0.71) to 0 during the follow-up of Ocrelizumab treatment (P < 0.0001). None of the patients had MRI activity during the treatment. Mean EDSS decreased from 1.75 (±1.09) to 1.20 (±0.63) from the initiation of Ocrelizumab to the last follow-up of the patients (P = 0.024). None of the patients had serious side effects, except one patient who experienced anaphylaxis. CONCLUSION: Ocrelizumab can be considered a safe and effective treatment option in highly active P-RRMS.
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Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Adulto , Humanos , Niño , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple Recurrente-Remitente/diagnóstico por imagen , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Esclerosis Múltiple Recurrente-Remitente/inducido químicamente , Anticuerpos Monoclonales Humanizados/uso terapéutico , Resultado del Tratamiento , Recurrencia , Factores Inmunológicos/uso terapéuticoRESUMEN
OBJECTIVE: In this study, our aim was to demonstrate the effect of sleep deprivation, short sleep, and awakening on photoparoxysmal responses (PPR) and eyelid myoclonia (EM) in patients with Epilepsy with Eyelid Myoclonia (E-EM). METHODS: E-EM patients with at least 1 year of follow-up in our clinic were included in the study. Video EEG(v-EEG) analyses were divided into three periods of wakefulness, sleep, and awakening. The PPR and onset of EMs were investigated. RESULTS: 32 patients met the study criteria, of which 56.3% (n = 18) were male. The mean age at disease onset was 7.7 ± 4.1 years. The mean age at EEG recording was 12.4 ± 4.0 years. EM was observed only on awakening in 78.1% of patients (n = 22), of which it was seen only during intermittent photic stimulation (IPS) in 43.7% (n = 14). Eye closure (EC) sensitivity was detected in all patients. The proportion of patients with a PPR was significantly higher on awakening than before sleep (p = 0.01). CONCLUSIONS: This study showed that EM is most prominent and sometimes can only be detected in the awakening period in E-EM. In order to detect E-EM, v-EEG recordings including both pre-sleep and post-sleep wakefulness periods should be recorded, with intermittent photic stimulation performed in both periods.
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Epilepsia , Mioclonía , Humanos , Masculino , Preescolar , Niño , Adolescente , Femenino , Privación de Sueño/complicaciones , Convulsiones , Epilepsia/complicaciones , Mioclonía/complicaciones , Mioclonía/diagnóstico , Electroencefalografía , Estimulación Luminosa , PárpadosRESUMEN
BACKGROUND: Paediatric-onset multiple sclerosis (POMS) is increasing worldwide and represents approximately 5% of all MS cases. Although this patient group has similar characteristics to the adult group, it is important for this patient group to receive effective treatment due to the early onset of cognitive involvement, higher lesion burden, and secondary progression at an earlier age than adults. In this study, we aimed to evaluate the factors that cause treatment change in POMS patients. MATERIAL AND METHOD: Adult patients with a first MS attack at age 18 years or younger who were followed up with the diagnosis of MS at the Clinical Neuroimmunology and Demyelinating Diseases outpatient clinic of Cerrahpasa Medical School between 1987 and 2020 were included in our study. Patient files were reviewed retrospectively, and demographic and clinical characteristics, imaging, first attack characteristics, and treatment change were noted. We included 269 patients with a definite diagnosis of MS in the study, and these patients were evaluated in two groups: negative for treatment change and positive for treatment change. RESULTS: Multifocal involvement was detected more frequently in the group with treatment change (p = 0,049). Cerebellar involvement as a first attack symptom was more common in male patients (p = 0,023) The age at first MS attack was found to be younger (p = 0,006), and the disease duration was longer in the positive for treatment change group (p = 0,003). Spinal cord involvement was more common in the positive for treatment change group (p = 0,016). Abnormal VEP findings were observed more frequently in the group without treatment change (p = 0.018). In multivariant analysis, spinal cord involvement, younger age at first attack, and abnormal VEP findings in the group without treatment change were found to be significant. Among the reasons for treatment change, the most common reason was radiological and clinical progression. CONCLUSION: The higher inflammatory load in POMS patients compared with adults necessitates early initiation of treatment in this group and timely treatment change to prevent disability. Furthermore, this patient group should be followed closely and receive effective treatment.
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Esclerosis Múltiple , Humanos , Adulto , Masculino , Niño , Adolescente , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/epidemiología , Estudios Retrospectivos , Cognición , Edad de Inicio , Imagen por Resonancia Magnética , Progresión de la EnfermedadRESUMEN
OBJECTIVE: To describe the clinical presentation and long-term clinical features of a molecularly confirmed cohort with Cohen syndrome. STUDY DESIGN: Twelve patients with Cohen syndrome aged 0.2-13.9 years from 8 families with a median follow-up of 7 years were enrolled to the study. Genetic analyses were made by VPS13B and whole-exome sequencing analyses. RESULTS: Biallelic VPS13B variants, including 3 nonsense, 1 frameshift, and 1 splice-site variant, and a multiexon deletion were detected. Prader-Willi syndrome-like features such as hypotonia, small hands, round face with full cheeks, almond-shaped eyes, and micrognathia were observed in all infantile patients. Beginning from age 4 years, it was noticed that the face gradually elongated and became oval. The typical facial features of Cohen syndrome such as a long face, beak-shaped nose, and open-mouth appearance with prominent upper central incisors became evident at age 9. Other Cohen syndrome features including retinopathy (11/11), neutropenia (11/12), truncal obesity (5/12), and myopia (5/11) were detected at the median ages of 7.8, 7, 7.5, and 5 years, respectively. Eleven patients aged older than 5 years at their last examination had severe speech delay. CONCLUSIONS: A differential diagnosis of Cohen syndrome in the infancy should be made with Prader-Willi syndrome, and that the typical facial features for Cohen syndrome is prominent at age 9 years, when retinopathy, neutropenia, and truncal obesity become evident. Moreover, adding the severe speech delay to the diagnostic criteria should be considered.
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Discapacidad Intelectual , Trastornos del Desarrollo del Lenguaje , Microcefalia , Miopía , Neutropenia , Síndrome de Prader-Willi , Degeneración Retiniana , Humanos , Niño , Hipotonía Muscular/diagnóstico , Hipotonía Muscular/genética , Proteínas de Transporte Vesicular/genética , Microcefalia/diagnóstico , Microcefalia/genética , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/genética , Degeneración Retiniana/genética , Miopía/diagnóstico , Miopía/genética , Obesidad/diagnóstico , Obesidad/genéticaRESUMEN
BACKGROUND: ADCY5 mutation is a clinical condition that has been described in limited numbers in the literature, causing hyperkinetic movement disorder, and may be sporadic or familial. PATIENT DESCRIPTION: This report looks at the involuntary movements that started early in life in a 5-year-old girl. RESULTS: Patient's electroensephalogram and cranial magnetic resonance imaging were normal. Metabolic scans were normal. ADCY5 mutation was found in whole exome sequencing of the patient who did not have a similar family history. CONCLUSION: Some features such as the worsening of involuntary movements after sleep and the presence of hypotonia in our patient suggested this mutation. Our patient is resistant to more than one drug. With this report, we aimed to pave the way for better understanding of the gene and the discovery of different treatment options.
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Adenilil Ciclasas , Discinesias , Humanos , Femenino , Preescolar , Adenilil Ciclasas/genética , Mutación/genética , Hipotonía Muscular , SueñoRESUMEN
OBJECTIVE: The study aimed to show the clinical characteristics and prognosis of the L1 syndrome in patients with L1CAM mutations in the extracellular region. MATERIALS AND METHODS: Three affected boys and their siblings and parents from a large family were included in this study. Genetic etiology was investigated by whole-exome sequencing in the index patient. The pathogenic variant was detected by whole-exome sequencing and was validated by Sanger sequencing in 3 patients and other family members. RESULTS: We present 2 brothers and their cousin with prenatal onset hydrocephalus, severe developmental and speech delay, corpus callosum agenesis/hypogenesis, epilepsia, and adducted thumbs. A hemizygous missense mutation NM_024003 (c.A2351G:p.Y784C) on exon 18 of L1CAM gene was found in the 3 patients and their carrier mother. This missense mutation in the conserved region of the second fibronectin type III-like repeats located in the extracellular region of L1CAM resulted in the severe phenotype of X-linked inherited L1 syndrome in the patients. CONCLUSION: L1 syndrome should be considered in the differential diagnosis of male children with intellectual disability, hydrocephalus, and adducted thumbs. While truncating mutations of L1CAM may cause a more severe phenotype, missense mutations cause milder forms. However, pathogenic missense mutations affecting key amino acid residues lead to severe phenotype likely.
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Heterozygous mutations in Bicaudal D2 Drosophila homolog 2 (BICD2) gene, encodes a vesicle transport protein involved in dynein-mediated movement along microtubules, are responsible for an exceedingly rare autosomal dominant spinal muscular atrophy type 2A which starts in the childhood and predominantly effects lower extremities. Recently, a more severe form, type 2B, has also been described. Here, we present a patient born to a consanguineous union and who suffered from intellectual disability, speech delay, epilepsy, happy facial expression, truncal obesity with tappering fingers, and joint hypermobility. Whole-exome sequencing analysis revealed a rare, homozygous missense mutation (c.731T>C; p.Leu244Pro) in BICD2 gene. This finding presents the first report in the literature for homozygous BICD2 mutations and its association with a Cohen-Like syndrome. Patients presenting with Cohen-Like phenotypes should be further interrogated for mutations in BICD2.
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Discapacidad Intelectual , Atrofia Muscular Espinal , Genes Dominantes , Humanos , Discapacidad Intelectual/genética , Proteínas Asociadas a Microtúbulos/genética , Atrofia Muscular Espinal/genética , Mutación , Mutación MissenseRESUMEN
OBJECTIVES: Diagnostic criteria of subacute sclerosing panencephalitis (SSPE) include myoclonus, a well-recognized clinical feature. Here, we studied the electrophysiological features of myoclonus with regards to disease staging in SSPE patients. METHODS: We included 10 patients diagnosed with SSPE between 2010 and 2018, along with 21 healthy subjects. All participants had detailed electrophysiological evaluation including polymyographic analysis, blink reflex after trigeminal stimulation, auditory startle response, startle response after somatosensory stimuli, F-waves, and long-loop reflexes. Clinical findings were retrieved from the medical records. RESULTS: Patients were categorized into Gascon stage 2B (n = 5, 50%), 2A (n = 2, 20%), 3B (n = 2, 20%) and 4A (n = 1, 10%) at the time of electrophysiological evaluation. Two patients had cortical myoclonus, four had possible cortico-subcortical myoclonus, and four had brainstem myoclonus. Patients were categorized into Gascon stages 2a and 2b had possible cortico-subcortical myoclonus (85.7%). However, none of the patients with stage 3b or 4a had possible cortico-subcortical subtype but all had the brainstem subtype. CONCLUSION: Association was seen between subtypes of myoclonus and clinical staging in SSPE. This suggests that myoclonus in SSPE may primarily involve the cortex and cortico-subcortical structures such as the thalamus at earlier stages of disease, and then involve more caudal structures as the disease progresses.
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Mioclonía , Panencefalitis Esclerosante Subaguda , Tronco Encefálico , Corteza Cerebral , Humanos , Mioclonía/diagnóstico , Panencefalitis Esclerosante Subaguda/complicaciones , Panencefalitis Esclerosante Subaguda/diagnósticoRESUMEN
PURPOSE: In patients diagnosed with epilepsy, decreased ratio of N-acetyl aspartate to creatine (NAA/Cr) measured in magnetic resonance spectroscopy (MRS) has been accepted as a sign of neuronal cell loss or dysfunction. In this study, we aimed to determine whether a similar neuronal cell loss is present in a group of encephalopathy with electrical status epilepticus in sleep (ESES) patients METHODS: We performed this case-control study at a tertiary pediatric neurology center with patients with ESES. Inclusion criteria for the patient group were as follows: 1) a spike-wave index of at least 50%, 2) acquired neuropsychological regression, 3) normal cranial MRI. Eventually, a total of 21 patients with ESES and 17 control subjects were enrolled in the study. MRI of all control subjects was also within normal limits. 3D Slicer program was used for the analysis of thalamic and brain volumes. LCModel spectral fitting software was used to analyze single-voxel MRS data from the right and left thalamus of the subjects. RESULTS: The mean age was 8.0 ± 1.88 years and 8.3 ± 1.70 years in ESES patients and the control subjects. After correcting for the main potential confounders (age and gender) with a linear regression model, NAA/Creatine ratio of the right thalamus was significantly lower in the ESES patient group compared to the healthy control group (p = 0.026). Likewise, the left thalamus NAA/Cr ratio was significantly lower in the ESES patient group than the healthy control group (p = 0.007). After correcting for age and gender, right thalamic volume was not statistically significantly smaller in ESES patients than in healthy controls (p = 0.337), but left thalamic volume was smaller in ESES patients than in healthy controls (p = 0.024). CONCLUSION: In ESES patients, the NAA/Creatine ratio, which is an indicator of neuronal cell loss or dysfunction in the right and left thalamus, which appears regular on MRI, was found to be significantly lower than the healthy control group. This metabolic-induced thalamic dysfunction, which was reported for the first time up to date, may play a role in ESES epileptogenesis.
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Estado Epiléptico , Estudios de Casos y Controles , Niño , Humanos , Imagen por Resonancia Magnética , Sueño , Estado Epiléptico/diagnóstico por imagen , Estado Epiléptico/etiología , Tálamo/diagnóstico por imagenRESUMEN
OBJECTIVES: The impact of coronavirus disease-19 (COVID-19) on metabolic outcome in patients with inborn errors of metabolism has rarely been discussed. Herein, we report a case with an acute encephalopathic crisis at the course of COVID-19 disease as the first sign of glutaric aciduria type 1 (GA-1). CASE PRESENTATION: A 9-month-old patient was admitted with encephalopathy and acute loss of acquired motor skills during the course of COVID-19 disease. She had lethargy, hypotonia, and choreoathetoid movements. In terms of COVID-19 encephalopathy, the reverse transcription-polymerase chain reaction assay test for COVID-19 was negative in cerebral spinal fluid. Brain imaging showed frontotemporal atrophy, bilateral subcortical and periventricular white matter, basal ganglia, and thalamic involvement. Elevated glutarylcarnitine in plasma and urinary excretion of glutaric and 3-OH-glutaric acids was noted. A homozygote mutation in the glutaryl-CoA dehydrogenase gene led to the diagnosis of GA-1. CONCLUSIONS: With this report, neurological damage associated with COVID-19 has been reported in GA-1 patients for the first time in literature.
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Errores Innatos del Metabolismo de los Aminoácidos/complicaciones , Encefalopatías Metabólicas/complicaciones , Encefalopatías/etiología , COVID-19/complicaciones , Glutaril-CoA Deshidrogenasa/deficiencia , Errores Innatos del Metabolismo de los Aminoácidos/diagnóstico por imagen , Errores Innatos del Metabolismo de los Aminoácidos/genética , Encéfalo/diagnóstico por imagen , Encefalopatías/complicaciones , Encefalopatías/diagnóstico por imagen , Encefalopatías Metabólicas/diagnóstico por imagen , Encefalopatías Metabólicas/genética , COVID-19/diagnóstico , COVID-19/diagnóstico por imagen , Prueba de COVID-19 , Carnitina/análogos & derivados , Carnitina/sangre , Carnitina/orina , Femenino , Pruebas Genéticas , Glutaratos/sangre , Glutaratos/orina , Glutaril-CoA Deshidrogenasa/genética , Humanos , Lactante , Imagen por Resonancia Magnética , Destreza Motora , Trastornos del Movimiento/etiología , Hipotonía Muscular/etiologíaAsunto(s)
Ceramidasa Alcalina/deficiencia , Encéfalo/diagnóstico por imagen , Leucoencefalopatías/genética , Sustancia Blanca/diagnóstico por imagen , Ceramidasa Alcalina/genética , Preescolar , Humanos , Leucoencefalopatías/diagnóstico por imagen , Espectroscopía de Resonancia Magnética , Masculino , MutaciónRESUMEN
PURPOSE: Cardiac and respiratory involvement constitutes serious complications of Duchenne muscular dystrophy (DMD). We hypothesized that obstructive sleep apnea syndrome (OSAS) may play a role in cardiac autonomic dysfunction in DMD. We sought to assess the presence of cardiac autonomic function in patients with DMD by analyzing heart rate variability (HRV) during polysomnography (PSG). METHODS: In a prospective study, all participants had whole-night PSG recorded and scored according to American Academy of Sleep Medicine guidelines. HRV analysis was performed on electrocardiography recordings from PSG recordings. RESULTS: Twelve consecutive males with DMD (mean age 9.0 ± 3.1 years, mean BMI 20.6 ± 4.8 kg/m2) and eight age-matched healthy males were enrolled. On clinical evaluation, 58% of patients with DMD had at least one symptom related to OSAS, such as snoring, witnessed apnea, or restless sleep. None of the controls had OSAS-related complaints. By PSG none of the controls had OSAS, while 42% of patients with DMD had OSAS (p = 0.004). Average R-R duration and mean percentage of successive R-R intervals > 50 ms values were significantly lower in patients with DMD than those in controls (p < 0.006). In patients with DMD and OSAS, LF/HF (low/high-frequency) ratio was significantly increased in NREM sleep compared with those in controls (p = 0.005). Higher apnea-hypopnea index and lower oxygen saturation showed significant correlations with higher LF power and LF/HF ratio (p < 0.001). CONCLUSION: Cardiac autonomic dysfunction is present in DMD, being more pronounced in the presence of OSAS.
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Distrofia Muscular de Duchenne/fisiopatología , Disautonomías Primarias/fisiopatología , Apnea Obstructiva del Sueño/fisiopatología , Niño , Humanos , Masculino , Estudios ProspectivosRESUMEN
To date, less than 10 pedigrees have been reported with ZNF335 mutations since it was discovered in 2012 and little is known about ZNF335-related clinical spectrum. We describe a 12 years old male patient who is only child of nonconsanguineous Turkish parents. Trio whole genome sequencing identified previously unreported compound heterozygous variants in ZNF335, namely, c.3889T > A p.(Ser1297Thr) and c.758G > A p.(Arg253Gln) where transmitted by his father and mother, respectively. Patient' magnetic resonance imaging findings were overlapping to those observed in the previous cases with ZNF335 mutations. Here we report the oldest patient with biallelic ZNF335 mutations. We recommend screening for ZNF335 defects in patients with basal ganglia anomaly, secondary white matter abnormalities and microcephaly.
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Ganglios Basales/patología , Cerebelo/patología , Proteínas de Unión al ADN/genética , Mutación , Factores de Transcripción/genética , Atrofia/diagnóstico por imagen , Atrofia/genética , Atrofia/patología , Ganglios Basales/diagnóstico por imagen , Cerebelo/diagnóstico por imagen , Niño , Humanos , Imagen por Resonancia Magnética , Masculino , LinajeRESUMEN
AIM: L-2-hydroxyglutaric aciduria is a slowly progressive neurometabolic disorder caused by an enzymatic deficiency of L-2-hydroxyglutarate dehydrogenase. Here, we aimed to evaluate the clinical, neuroradiologic, and genotypic characteristics of patients with L-2-hydroxyglutaric aciduria who were followed in our outpatient clinic. MATERIAL AND METHODS: Twenty-five patients with L-2-hydroxyglutaric aciduria were enrolled in the study. Data regarding demographic, clinical, and neuroradiologic findings and molecular analysis were evaluated retrospectively. RESULTS: The mean age of patients at the time of diagnosis was 12.09±8.02 years, whereas the mean age at the time of the first symptoms was 39.47±29.96 months. Diagnostic delay was found as 9.95±7.78 years. Developmental delay, decrease in school success, and seizures were the most common initial symptoms; however, behavioral problems and seizures became more prominent in the disease course. At the time of diagnosis, mental retardation and at least one pathologic cerebellar finding were detected in all symptomatic patients. Three patients developed brain tumors. The most common neuroimaging findings were subcortical white matter changes and cerebellar dentate nucleus involvement. In one patient, there was only isolated basal ganglia involvement without white matter lesions. Patients with similar genotypic features exhibited different clinical and radiologic findings. CONCLUSION: Although clinical symptoms appear early in L-2-hydroxyglutaric aciduria, there is approximately a ten-year delay in diagnosis. In subjects in whom brain tumor is detected in early childhood, L-2-hydroxyglutaric aciduria should be considered in the differential diagnosis in the presence of mental retardation accompanied by developmental delay, cerebellar and pyramidal findings, and behavior disorders in a wide spectrum ranging from autism spectrum disorder to psychosis. In patients with L-2-hydroxyglutaric aciduria, incipient headache, tinnitus, altered consciousness, and seizures can be indicative of brain tumors.
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In patients with spinal muscular atrophy (SMA), obstructive sleep apnea syndrome (OSAS) constitutes an important cause of cardiovascular morbidity and mortality. We investigated heart rate variability (HRV) to evaluate the effects of non-invasive mechanical ventilation on cardiac autonomic dysfunction in patients with SMA and OSAS. Six patients with SMA (type 1 and 2) and six age- and sex-matched healthy children were consecutively enrolled. A whole-night diagnostic polysomnography was performed, and SMA patients with OSAS were given non-invasive mechanical ventilation therapy. HRV analysis was performed on the basis of whole-night electrocardiography recordings via a computer-base program. Apnea-hypopnea index (AHI) was 9.2⯱â¯6.2/hr in SMA patients, while it was 0.4⯱â¯0.5/hr in controls (pâ¯=â¯0.036). All SMA patients had OSAS, while none of the controls had OSAS (pâ¯=â¯0.012). Mean percentage of successive R wave of QRS complex (R-R) intervals>50â¯ms was significantly lower in SMA patients than those in controls (pâ¯=â¯0.031). Significant correlations were found between AHI and high-frequency power, low/high-frequency ratio in wakefulness and in sleep (p<0.05). Repeated HRV analysis in SMA patients following OSAS therapy showed significant reductions in average R-R duration (pâ¯=â¯0.028) and percentage of successive R-R intervals>50â¯ms (pâ¯=â¯0.043). Our study demonstrates the beneficial effects of non-invasive mechanical ventilation on cardiac autonomic dysfunction in SMA patients with OSAS.
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Enfermedades del Sistema Nervioso Autónomo/terapia , Cardiopatías/terapia , Atrofia Muscular Espinal/terapia , Ventilación no Invasiva , Apnea Obstructiva del Sueño/terapia , Enfermedades del Sistema Nervioso Autónomo/diagnóstico , Enfermedades del Sistema Nervioso Autónomo/etiología , Niño , Preescolar , Electrocardiografía , Cardiopatías/diagnóstico , Cardiopatías/etiología , Frecuencia Cardíaca/fisiología , Humanos , Lactante , Masculino , Atrofia Muscular Espinal/complicaciones , Evaluación de Resultado en la Atención de Salud , Polisomnografía , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/etiologíaRESUMEN
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a serious autoimmune disorder characterized by psychiatric symptoms, seizures and movement disorder. Predisposing factors have been reported since the time it was described, and its pathophysiology has been tried to be clarified over the years. Although overlap with other demyelinating diseases had been reported, such an association between Multiple Sclerosis (MS) anti ANTI-NMDAR encephalitis is limited to only a few case reports. In this article, a patient diagnosed with relapsing remitting multiple sclerosis (RRMS) for ten years who then developed NMDA-R encephalitis while on disease modifying treatment will be presented and possible common pathophysiology with previously reported literature will be discussed.