RESUMO
BACKGROUND: Acute flaccid paralysis (AFP) is characterized by rapidly progressive limb weakness with low muscle tone. It has a broad differential diagnosis, which includes acute flaccid myelitis (AFM), a rare polio-like condition that mainly affects young children. Differentiation between AFM and other causes of AFP may be difficult, particularly at onset of disease. Here, we evaluate the diagnostic criteria for AFM and compare AFM to other causes of acute weakness in children, aiming to identify differentiating clinical and diagnostic features. METHODS: The diagnostic criteria for AFM were applied to a cohort of children with acute onset of limb weakness. An initial classification based on positive diagnostic criteria was compared to the final classification, based on application of features suggestive for an alternative diagnosis and discussion with expert neurologists. Cases classified as definite, probable, or possible AFM or uncertain, were compared to cases with an alternative diagnosis. RESULTS: Of 141 patients, seven out of nine patients initially classified as definite AFM, retained this label after further classification. For probable AFM, this was 3/11, for possible AFM 3/14 and for uncertain 11/43. Patients initially classified as probable or possible AFM were most commonly diagnosed with transverse myelitis (16/25). If the initial classification was uncertain, Guillain-Barré syndrome was the most common diagnosis (31/43). Clinical and diagnostic features not included in the diagnostic criteria, were often used for the final classification. CONCLUSION: The current diagnostic criteria for AFM usually perform well, but additional features are sometimes required to distinguish AFM from other conditions.
Assuntos
Enterovirus Humano D , Infecções por Enterovirus , Mielite Transversa , Doenças Neuromusculares , Criança , Humanos , Pré-Escolar , alfa-Fetoproteínas , Infecções por Enterovirus/diagnóstico , Doenças Neuromusculares/diagnóstico , Doenças Neuromusculares/complicações , Mielite Transversa/diagnóstico , Debilidade Muscular , Paralisia/diagnóstico , Paralisia/etiologiaRESUMO
We report detailed functional analyses and genotype-phenotype correlations in 392 individuals carrying disease-causing variants in SCN8A, encoding the voltage-gated Na+ channel Nav1.6, with the aim of describing clinical phenotypes related to functional effects. Six different clinical subgroups were identified: Group 1, benign familial infantile epilepsy (n = 15, normal cognition, treatable seizures); Group 2, intermediate epilepsy (n = 33, mild intellectual disability, partially pharmaco-responsive); Group 3, developmental and epileptic encephalopathy (n = 177, severe intellectual disability, majority pharmaco-resistant); Group 4, generalized epilepsy (n = 20, mild to moderate intellectual disability, frequently with absence seizures); Group 5, unclassifiable epilepsy (n = 127); and Group 6, neurodevelopmental disorder without epilepsy (n = 20, mild to moderate intellectual disability). Those in Groups 1-3 presented with focal or multifocal seizures (median age of onset: 4 months) and focal epileptiform discharges, whereas the onset of seizures in patients with generalized epilepsy was later (median: 42 months) with generalized epileptiform discharges. We performed functional studies expressing missense variants in ND7/23 neuroblastoma cells and primary neuronal cultures using recombinant tetrodotoxin-insensitive human Nav1.6 channels and whole-cell patch-clamping. Two variants causing developmental and epileptic encephalopathy showed a strong gain-of-function (hyperpolarizing shift of steady-state activation, strongly increased neuronal firing rate) and one variant causing benign familial infantile epilepsy or intermediate epilepsy showed a mild gain-of-function (defective fast inactivation, less increased firing). In contrast, all three variants causing generalized epilepsy induced a loss-of-function (reduced current amplitudes, depolarizing shift of steady-state activation, reduced neuronal firing). Functional effects were known for 170 individuals. All 136 individuals carrying a functionally tested gain-of-function variant had either focal (n = 97, Groups 1-3) or unclassifiable (n = 39) epilepsy, whereas 34 individuals with a loss-of-function variant had either generalized (n = 14), no (n = 11) or unclassifiable (n = 6) epilepsy; only three had developmental and epileptic encephalopathy. Computational modelling in the gain-of-function group revealed a significant correlation between the severity of the electrophysiological and clinical phenotypes. Gain-of-function variant carriers responded significantly better to sodium channel blockers than to other anti-seizure medications, and the same applied for all individuals in Groups 1-3. In conclusion, our data reveal clear genotype-phenotype correlations between age at seizure onset, type of epilepsy and gain- or loss-of-function effects of SCN8A variants. Generalized epilepsy with absence seizures is the main epilepsy phenotype of loss-of-function variant carriers and the extent of the electrophysiological dysfunction of the gain-of-function variants is a main determinant of the severity of the clinical phenotype in focal epilepsies. Our pharmacological data indicate that sodium channel blockers present a treatment option in SCN8A-related focal epilepsy with onset in the first year of life.
Assuntos
Epilepsia Generalizada , Síndromes Epilépticas , Deficiência Intelectual , Canal de Sódio Disparado por Voltagem NAV1.6 , Epilepsia Generalizada/tratamento farmacológico , Epilepsia Generalizada/genética , Síndromes Epilépticas/tratamento farmacológico , Síndromes Epilépticas/genética , Estudos de Associação Genética , Humanos , Lactente , Deficiência Intelectual/genética , Mutação , Canal de Sódio Disparado por Voltagem NAV1.6/genética , Prognóstico , Convulsões/tratamento farmacológico , Convulsões/genética , Bloqueadores dos Canais de Sódio/uso terapêuticoRESUMO
The ketogenic diet (KD), containing high levels of fat and low levels of carbohydrates, has been used to treat refractory epilepsy since the 1920s. In the past few decades, there has been more interest in less restrictive KDs such as the modified Atkins diet (MAD). PURPOSE: Our aim was to review all evidence regarding the efficacy and tolerability of the KD and MAD from randomized controlled trials (RCTs) in children and adolescents with refractory epilepsy. METHODS: We reviewed the current literature using Cochrane, EMBASE, and MEDLINE (using PubMed). We implemented predefined criteria regarding dataextraction and study quality. RESULTS: We identified five RCTs that generated seven publications and recruited 472 children and adolescents with refractory epilepsy (≤ 18 years). The primary outcome (seizure frequency reduction (SFR) ≥ 50%) was attained in 35-56.1% of the participants in the intervention group, compared with 6-18.2% in the control group. Our meta-analysis underlined the significant efficacy of the KD compared with the control group: RR = 5.1 (95% CI 3.18-8.21, p < 0.001). Additionally, only two studies mentioned possible biomarkers to objectively evaluate the efficacy. Secondary outcomes, such as seizure severity and quality of life, were studied in three trials, leading to indecisive generalization of these findings. Gastro-intestinal adverse effects were the most prevalent, and no severe adverse effects were reported. CONCLUSION: Despite the heterogeneity between all studies, the beneficial results underline that dietary interventions should be considered for children and adolescents with refractory epilepsy who are not eligible for epilepsy surgery. Future studies should be multi-center and long-term, and evaluate potential biomarkers and adverse effects.
Assuntos
Dieta Cetogênica , Epilepsia Resistente a Medicamentos , Epilepsia , Adolescente , Criança , Humanos , Convulsões , Resultado do TratamentoRESUMO
BACKGROUND: Idiopathic intracranial hypertension (IIH) is a neurological syndrome characterized by elevated intracranial pressure in the absence of intracerebral abnormalities or hydrocephalus. CASE DESCRIPTION: A 17-year-old girl gained more than 25 kg in weight during treatment with risperidone and subsequently developed headache, diplopia and loss of vision due to IIH. After insertion of a ventriculoperitoneal drain and discontinuation of risperidone she lost weight and her symptoms improved. Her visual functions recovered almost fully during follow-up. CONCLUSION: Patients with IIH are mainly overweight young women who present with raised intracranial pressure evidenced by headache, nausea, vomiting and vision disturbances. Prescribed medication-induced weight gain may lead to IIH. Treatment of IIH should be focused on the prevention of severe and irreversible loss of vision.
Assuntos
Antipsicóticos/efeitos adversos , Obesidade/complicações , Pseudotumor Cerebral/diagnóstico , Risperidona/efeitos adversos , Aumento de Peso , Adolescente , Antipsicóticos/uso terapêutico , Feminino , Cefaleia , Humanos , Obesidade/induzido quimicamente , Pseudotumor Cerebral/etiologia , Risperidona/uso terapêuticoRESUMO
We report a case of a 93-year-old man, who presented with limb-shaking transient ischemic attacks (TIAs) after orthostatic position change or turning his head to the left. The limb-shaking TIAs resulted from external compression of the carotid artery. Contrast-enhanced magnetic resonance angiography of the head and neck and Doppler ultrasound examination of the thyroid gland revealed a large cystic nodule in the right thyroid lobe, resulting in compression and posterior displacement of the right common carotid artery. Clinicians should be aware that limb-shaking TIAs can not only result from obstructive extracerebral or intracerebral artery disease, but also from external compression of the carotid artery.