Introduction: F-waves are late responses to motor nerve stimulation with relevant applications in... more Introduction: F-waves are late responses to motor nerve stimulation with relevant applications in the electrodiagnostic evaluation of the proximal tracts of the peripheral nervous system such as the brachial or lumbosacral plexi and the spinal roots. In our clinical experience, F-waves from stimulation of the radial nerve recorded from the anconeus muscle can be useful in the evaluation of C7 radiculopathies and of posterior cord and middle trunk plexopathies. Objectives: To report normal values of anconeus muscle F-waves (AFWs). Methods: We tested 25 healthy adults (15 F, 10 M; aged 18 54 years; height: 158 178 cm) on both arms. We recorded the anconeus muscle on the dorsal surface of the forearm (bipolar montage with G1 4 cm distal to the olecranon and G2 placed 2 3 cm further distally). The radial nerve was stimulated 4 cm proximal to the olecranon with 0.2 ms square waves at intensity of 120% of the one required for a maximal M response. Analysis was performed on one limb per subject selected randomly. The measurements consisted of (1) F-wave persistence (PERS); (2) minimum (FMIN), (3) mean (FMEAN) and (4) maximum (FMAX) F-wave latencies and the inter-side difference of persistence (D-PERS) and of FMIN (D-FMIN). Additionally we evaluated the distal motor latency (DLM) and amplitude (M-AMPL) of M-responses from the anconeus muscle. Results: All parameters had normal distributions (Shapiro-Wilk’s W test). Asymmetry and kurtosis were negligible. FMIN, FMEAN and FMAX values correlated significantly with the subjects’ height (r = 0.75, r = 0.76 and r = 0.76 respectively), showing an increase of around 0.1 ms per every cm of height. We report hereafter the mean±SD of all parameters. PERS: 39.4±23.0 ms. FMIN: 17.8±2.1 ms. FMEAN: 18.7±1.9 ms. FMAX: 19.8±1.7 ms. D-PERS: 11.5±8.7 ms. D-FMIN: 0.9±0.9 ms. DLM: 3.0±0.4. M-AMPL: 6.5±1.8. Conclusions: AFWs are a reliable and repeatable electrodiagnostic technique of considerable potential clinical use.
Myotonic dystrophy type 1 (DM1) is an autosomal dominant inheritable disease associated with an e... more Myotonic dystrophy type 1 (DM1) is an autosomal dominant inheritable disease associated with an expansion of CTG repeats in the 3' UTR of the DMPK gene. The subject is an 11-year-old girl with atypical myopathy. Because the proband's family has a positive DM1 history, a molecular-genetic analysis for DM1 was performed. This study showed that proband had a small DMPK expansion (91 CTG repeats) although the observed myopathy would not normally be associated with DM1. These results show how the phenotypic manifestation of DM1 can have unusual symptoms with a completely unexpected relationship to genotype.
It is unclear whether the heart is affected in pediatric patients with milder forms of spinal mus... more It is unclear whether the heart is affected in pediatric patients with milder forms of spinal muscular atrophy (SMA). Therefore, we aimed to determine the presence of any cardiac abnormalities in these patients.
It is unclear whether the heart is affected in pediatric patients with milder forms of spinal mus... more It is unclear whether the heart is affected in pediatric patients with milder forms of spinal muscular atrophy (SMA). Therefore, we aimed to determine the presence of any cardiac abnormalities in these patients.
Mutations in the OPHN1 gene cause a rare X‐linked recessive neurodevelopmental disorder character... more Mutations in the OPHN1 gene cause a rare X‐linked recessive neurodevelopmental disorder characterized by intellectual disability, variably associated with cerebellar hypoplasia and distinctive facial appearance. In most of cases so far reported, the identified genomic variants involve the region encoding the central RhoGAP domain of the oligophrenin‐1 protein, and are predicted to result in a complete loss of function. By using a NGS‐based diagnostic approach, we identified three male and a female patients from two unrelated families carrying novel non‐disruptive OPHN1 variants (the in‐frame c.116_127 deletion and the missense c.2129C>T change, respectively), affecting either the BAR domain or the C‐terminus proline‐rich domain of the protein. Clinical and neuroimaging findings in the patients recapitulated the main features of OPHN1‐related syndrome, including developmental delay, intellectual disability, behavioral disorder, dysmorphic features, seizures, cerebellar hypoplasia,...
BackgroundDominant and recessive variants in the KIF1A gene on chromosome 2q37.3 are associated w... more BackgroundDominant and recessive variants in the KIF1A gene on chromosome 2q37.3 are associated with several phenotypes, although only three syndromes are currently listed in the OMIM classification: hereditary sensory and autonomic neuropathy type 2 and spastic paraplegia type 30, both recessively inherited, and mental retardation type 9 with dominant inheritance.MethodsIn this retrospective multicentre study, we describe the clinical, neuroradiological and genetic features of 19 Caucasian patients (aged 3–65 years) harbouring heterozygous KIF1A variants, and extensively review the available literature to improve current classification of KIF1A-related disorders.ResultsPatients were divided into two groups. Group 1 comprised patients with a complex phenotype with prominent pyramidal signs, variably associated in all but one case with additional features (ie, epilepsy, ataxia, peripheral neuropathy, optic nerve atrophy); conversely, patients in group 2 presented an early onset or co...
Kv1.2 channels, encoded by the KCNA2 gene, are localized in the central and peripheral nervous sy... more Kv1.2 channels, encoded by the KCNA2 gene, are localized in the central and peripheral nervous system, where they regulate neuronal excitability. Recently, heterozygous mutations in KCNA2 have been associated with a spectrum of symptoms extending from epileptic encephalopathy, intellectual disability, and cerebellar ataxia. Patients are treated with a combination of antiepileptic drugs and 4-aminopyridine (4-AP) has been recently trialed in specific cases. We identified a novel variant in KCNA2, E236K, in a Serbian proband with non-progressive congenital ataxia and early onset epilepsy, treated with sodium valproate. To ascertain the pathogenicity of E236K mutation and to verify its sensitivity to 4-AP, we transfected HEK 293 cells with Kv1.2 WT or E236K cDNAs and recorded potassium currents through the whole-cell patch-clamp. In silico analysis supported the electrophysiological data. E236K channels showed voltage-dependent activation shifted towards negative potentials and slower ...
BackgroundPontocerebellar hypoplasias (PCH) comprise a group of genetically heterogeneous disorde... more BackgroundPontocerebellar hypoplasias (PCH) comprise a group of genetically heterogeneous disorders characterised by concurrent hypoplasia of the pons and the cerebellum and variable clinical and imaging features. The current classification includes 13 subtypes, with ~20 known causative genes. Attempts have been made to delineate the phenotypic spectrum associated to specific PCH genes, yet clinical and neuroradiological features are not consistent across studies, making it difficult to define gene-specific outcomes.MethodsWe performed deep clinical and imaging phenotyping in 56 probands with a neuroradiological diagnosis of PCH, who underwent NGS-based panel sequencing of PCH genes and MLPA for CASK rearrangements. Next, we conducted a phenotype-based unsupervised hierarchical cluster analysis to investigate associations between genes and specific phenotypic clusters.ResultsA genetic diagnosis was obtained in 43 probands (77%). The most common causative gene was CASK, which account...
Introduction: F-waves are late responses to motor nerve stimulation with relevant applications in... more Introduction: F-waves are late responses to motor nerve stimulation with relevant applications in the electrodiagnostic evaluation of the proximal tracts of the peripheral nervous system such as the brachial or lumbosacral plexi and the spinal roots. In our clinical experience, F-waves from stimulation of the radial nerve recorded from the anconeus muscle can be useful in the evaluation of C7 radiculopathies and of posterior cord and middle trunk plexopathies. Objectives: To report normal values of anconeus muscle F-waves (AFWs). Methods: We tested 25 healthy adults (15 F, 10 M; aged 18 54 years; height: 158 178 cm) on both arms. We recorded the anconeus muscle on the dorsal surface of the forearm (bipolar montage with G1 4 cm distal to the olecranon and G2 placed 2 3 cm further distally). The radial nerve was stimulated 4 cm proximal to the olecranon with 0.2 ms square waves at intensity of 120% of the one required for a maximal M response. Analysis was performed on one limb per subject selected randomly. The measurements consisted of (1) F-wave persistence (PERS); (2) minimum (FMIN), (3) mean (FMEAN) and (4) maximum (FMAX) F-wave latencies and the inter-side difference of persistence (D-PERS) and of FMIN (D-FMIN). Additionally we evaluated the distal motor latency (DLM) and amplitude (M-AMPL) of M-responses from the anconeus muscle. Results: All parameters had normal distributions (Shapiro-Wilk’s W test). Asymmetry and kurtosis were negligible. FMIN, FMEAN and FMAX values correlated significantly with the subjects’ height (r = 0.75, r = 0.76 and r = 0.76 respectively), showing an increase of around 0.1 ms per every cm of height. We report hereafter the mean±SD of all parameters. PERS: 39.4±23.0 ms. FMIN: 17.8±2.1 ms. FMEAN: 18.7±1.9 ms. FMAX: 19.8±1.7 ms. D-PERS: 11.5±8.7 ms. D-FMIN: 0.9±0.9 ms. DLM: 3.0±0.4. M-AMPL: 6.5±1.8. Conclusions: AFWs are a reliable and repeatable electrodiagnostic technique of considerable potential clinical use.
Myotonic dystrophy type 1 (DM1) is an autosomal dominant inheritable disease associated with an e... more Myotonic dystrophy type 1 (DM1) is an autosomal dominant inheritable disease associated with an expansion of CTG repeats in the 3' UTR of the DMPK gene. The subject is an 11-year-old girl with atypical myopathy. Because the proband's family has a positive DM1 history, a molecular-genetic analysis for DM1 was performed. This study showed that proband had a small DMPK expansion (91 CTG repeats) although the observed myopathy would not normally be associated with DM1. These results show how the phenotypic manifestation of DM1 can have unusual symptoms with a completely unexpected relationship to genotype.
It is unclear whether the heart is affected in pediatric patients with milder forms of spinal mus... more It is unclear whether the heart is affected in pediatric patients with milder forms of spinal muscular atrophy (SMA). Therefore, we aimed to determine the presence of any cardiac abnormalities in these patients.
It is unclear whether the heart is affected in pediatric patients with milder forms of spinal mus... more It is unclear whether the heart is affected in pediatric patients with milder forms of spinal muscular atrophy (SMA). Therefore, we aimed to determine the presence of any cardiac abnormalities in these patients.
Mutations in the OPHN1 gene cause a rare X‐linked recessive neurodevelopmental disorder character... more Mutations in the OPHN1 gene cause a rare X‐linked recessive neurodevelopmental disorder characterized by intellectual disability, variably associated with cerebellar hypoplasia and distinctive facial appearance. In most of cases so far reported, the identified genomic variants involve the region encoding the central RhoGAP domain of the oligophrenin‐1 protein, and are predicted to result in a complete loss of function. By using a NGS‐based diagnostic approach, we identified three male and a female patients from two unrelated families carrying novel non‐disruptive OPHN1 variants (the in‐frame c.116_127 deletion and the missense c.2129C>T change, respectively), affecting either the BAR domain or the C‐terminus proline‐rich domain of the protein. Clinical and neuroimaging findings in the patients recapitulated the main features of OPHN1‐related syndrome, including developmental delay, intellectual disability, behavioral disorder, dysmorphic features, seizures, cerebellar hypoplasia,...
BackgroundDominant and recessive variants in the KIF1A gene on chromosome 2q37.3 are associated w... more BackgroundDominant and recessive variants in the KIF1A gene on chromosome 2q37.3 are associated with several phenotypes, although only three syndromes are currently listed in the OMIM classification: hereditary sensory and autonomic neuropathy type 2 and spastic paraplegia type 30, both recessively inherited, and mental retardation type 9 with dominant inheritance.MethodsIn this retrospective multicentre study, we describe the clinical, neuroradiological and genetic features of 19 Caucasian patients (aged 3–65 years) harbouring heterozygous KIF1A variants, and extensively review the available literature to improve current classification of KIF1A-related disorders.ResultsPatients were divided into two groups. Group 1 comprised patients with a complex phenotype with prominent pyramidal signs, variably associated in all but one case with additional features (ie, epilepsy, ataxia, peripheral neuropathy, optic nerve atrophy); conversely, patients in group 2 presented an early onset or co...
Kv1.2 channels, encoded by the KCNA2 gene, are localized in the central and peripheral nervous sy... more Kv1.2 channels, encoded by the KCNA2 gene, are localized in the central and peripheral nervous system, where they regulate neuronal excitability. Recently, heterozygous mutations in KCNA2 have been associated with a spectrum of symptoms extending from epileptic encephalopathy, intellectual disability, and cerebellar ataxia. Patients are treated with a combination of antiepileptic drugs and 4-aminopyridine (4-AP) has been recently trialed in specific cases. We identified a novel variant in KCNA2, E236K, in a Serbian proband with non-progressive congenital ataxia and early onset epilepsy, treated with sodium valproate. To ascertain the pathogenicity of E236K mutation and to verify its sensitivity to 4-AP, we transfected HEK 293 cells with Kv1.2 WT or E236K cDNAs and recorded potassium currents through the whole-cell patch-clamp. In silico analysis supported the electrophysiological data. E236K channels showed voltage-dependent activation shifted towards negative potentials and slower ...
BackgroundPontocerebellar hypoplasias (PCH) comprise a group of genetically heterogeneous disorde... more BackgroundPontocerebellar hypoplasias (PCH) comprise a group of genetically heterogeneous disorders characterised by concurrent hypoplasia of the pons and the cerebellum and variable clinical and imaging features. The current classification includes 13 subtypes, with ~20 known causative genes. Attempts have been made to delineate the phenotypic spectrum associated to specific PCH genes, yet clinical and neuroradiological features are not consistent across studies, making it difficult to define gene-specific outcomes.MethodsWe performed deep clinical and imaging phenotyping in 56 probands with a neuroradiological diagnosis of PCH, who underwent NGS-based panel sequencing of PCH genes and MLPA for CASK rearrangements. Next, we conducted a phenotype-based unsupervised hierarchical cluster analysis to investigate associations between genes and specific phenotypic clusters.ResultsA genetic diagnosis was obtained in 43 probands (77%). The most common causative gene was CASK, which account...
Uploads
Papers by Vesna Brankovic