RESUMO
The branched-chain amino acid (BCAA) is a group of essential amino acids that are involved in maintaining the energy balance of a human being as well as the homoeostasis of GABAergic, glutamatergic, serotonergic and dopaminergic systems. Disruption of these systems has been associated with the pathophysiology of autism while low levels of these amino acids have been discovered in patients with autism. A pilot open-label, prospective, follow-up study of the use of BCAA in children with autistic behaviour was carried out. Fifty-five children between the ages of 6 and 18 participated in the study from May 2015 to May 2018. We used a carbohydrate-free BCAA-powdered mixture containing 45·5 g of leucine, 30 g of isoleucine and 24·5 g of valine in a daily dose of 0·4 g/kg of body weight which was administered every morning. Following the initiation of BCAA administration, children were submitted to a monthly psychological examination. Beyond the 4-week mark, BCAA were given to thirty-two people (58·18 %). Six of them (10·9 %) discontinued after 4-10 weeks owing to lack of improvement. The remaining twenty-six children (47·27 %) who took BCAA for longer than 10 weeks displayed improved social behaviour and interactions, as well as improvements in their speech, cooperation, stereotypy and, principally, their hyperactivity. There were no adverse reactions reported during the course of the treatment. Although these data are preliminary, there is some evidence that BCAA could be used as adjunctive treatment to conventional therapeutic methods for the management of autism.
Assuntos
Aminoácidos de Cadeia Ramificada , Transtorno Autístico , Criança , Humanos , Adolescente , Transtorno Autístico/tratamento farmacológico , Projetos Piloto , Seguimentos , Estudos Prospectivos , LeucinaRESUMO
BACKGROUND: There are limited data regarding the prevalence of distinct clinical, neuroimaging and genetic markers among patients diagnosed with cerebral amyloid angiopathy-related inflammation (CAA-ri). We sought to determine the prevalence of clinical, radiological, genetic and cerebrospinal fluid biomarker findings in patients with CAA-ri. METHODS: A systematic review and meta-analysis of published studies including patients with CAA-ri was conducted to determine the prevalence of clinical, neuroimaging, genetic and cerebrospinal fluid biomarker findings. Subgroup analyses were performed based on (1) prospective or retrospective study design and (2) CAA-ri diagnosis with or without available biopsy. We pooled the prevalence rates using random-effects models and assessed the heterogeneity using Cochran-Q and I2-statistics. RESULTS: We identified 4 prospective and 17 retrospective cohort studies comprising 378 patients with CAA-ri (mean age, 71.5 years; women, 52%). The pooled prevalence rates were as follows: cognitive decline at presentation 70% ([95% CI, 54%-84%]; I2=82%), focal neurological deficits 55% ([95% CI, 40%-70%]; I2=82%), encephalopathy 54% ([95% CI, 39%-68%]; I2=43%), seizures 37% ([95% CI, 27%-49%]; I2=65%), headache 31% ([95% CI, 22%-42%]; I2=58%), T2/fluid-attenuated inversion recovery-hyperintense white matter lesions 98% ([95% CI, 93%-100%]; I2=44%), lobar cerebral microbleeds 96% ([95% CI, 92%-99%]; I2=25%), gadolinium enhancing lesions 54% ([95% CI, 42%-66%]; I2=62%), cortical superficial siderosis 51% ([95% CI, 34%-68%]; I2=77%) and lobar macrohemorrhage 40% ([95% CI, 11%-73%]; I2=88%). The prevalence rate of the ApoE (Apolipoprotein E) ε4/ε4 genotype was 34% ([95% CI, 17%-53%]; I2=76%). Subgroup analyses demonstrated no differences in these prevalence rates based on study design and diagnostic strategy. CONCLUSIONS: Cognitive decline was the most common clinical feature. Hyperintense T2/fluid-attenuated inversion recovery white matter lesions and lobar cerebral microbleeds were by far the most prevalent neuroimaging findings. Thirty-four percent of patients with CAA-ri have homozygous ApoE ε4/ε4 genotype and scarce data exist regarding the cerebrospinal fluid biomarkers and its significance in these patients.
Assuntos
Angiopatia Amiloide Cerebral , Hemorragia Cerebral , Humanos , Feminino , Idoso , Estudos Retrospectivos , Marcadores Genéticos , Estudos Prospectivos , Hemorragia Cerebral/patologia , Angiopatia Amiloide Cerebral/diagnóstico por imagem , Angiopatia Amiloide Cerebral/genética , Angiopatia Amiloide Cerebral/patologia , Neuroimagem , Inflamação/diagnóstico por imagem , Inflamação/genética , Inflamação/patologia , Imageamento por Ressonância Magnética/métodosRESUMO
BACKGROUND: Limited data exist regarding the prevalence of clinical and neuroimaging manifestations among patients diagnosed with cerebral amyloid angiopathy (CAA). We sought to determine the prevalence of clinical phenotypes and radiological markers in patients with CAA. METHODS: Systematic review and meta-analysis of studies including patients with CAA was conducted to primarily assess the prevalence of clinical phenotypes and neuroimaging markers as available in the included studies. Sensitivity analyses were performed based on the (1) retrospective or prospective study design and (2) probable or unspecified CAA status. We pooled the prevalence rates using random-effects models and assessed the heterogeneity using the Cochran Q and I2 statistics. RESULTS: We identified 12 prospective and 34 retrospective studies including 7159 patients with CAA. The pooled prevalence rates were cerebral microbleeds (52% [95% CI, 43%-60%]; I2=93%), cortical superficial siderosis (49% [95% CI, 38%-59%]; I2=95%), dementia or mild cognitive impairment (50% [95% CI, 35%-65%]; I2=97%), intracerebral hemorrhage (ICH; 44% [95% CI, 27%-61%]; I2=98%), transient focal neurological episodes (48%; 10 studies [95% CI, 29%-67%]; I2=97%), lacunar infarcts (30% [95% CI, 25%-36%]; I2=78%), high grades of perivascular spaces located in centrum semiovale (56% [95% CI, 44%-67%]; I2=88%) and basal ganglia (21% [95% CI, 2%-51%]; I2=98%), and white matter hyperintensities with moderate or severe Fazekas score (53% [95% CI, 40%-65%]; I2=91%). The only neuroimaging marker that was associated with higher odds of recurrent ICH was cortical superficial siderosis (odds ratio, 1.57 [95% CI, 1.01-2.46]; I2=47%). Sensitivity analyses demonstrated a higher prevalence of ICH (53% versus 16%; P=0.03) and transient focal neurological episodes (57% versus 17%; P=0.03) among retrospective studies compared with prospective studies. No difference was documented between the prevalence rates based on the CAA status. CONCLUSIONS: Approximately one-half of hospital-based cohort of CAA patients was observed to have cerebral microbleeds, cortical superficial siderosis, mild cognitive impairment, dementia, ICH, or transient focal neurological episodes. Cortical superficial siderosis was the only neuroimaging marker that was associated with higher odds of ICH recurrence. Future population-based studies among well-defined CAA cohorts are warranted to corroborate our findings.
Assuntos
Angiopatia Amiloide Cerebral , Demência , Siderose , Angiopatia Amiloide Cerebral/complicações , Angiopatia Amiloide Cerebral/diagnóstico por imagem , Angiopatia Amiloide Cerebral/epidemiologia , Hemorragia Cerebral/complicações , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/epidemiologia , Demência/complicações , Humanos , Imageamento por Ressonância Magnética , Neuroimagem , Prevalência , Estudos Prospectivos , Estudos Retrospectivos , Siderose/complicaçõesRESUMO
Antibodies against glutamate decarboxylase (GAD-Abs), especially GAD65 antibodies, are associated with limbic encephalitis (LE) manifested by temporal lobe epilepsy and neuropsychological deficits. We present the case of a 42-year-old Greek woman with nonparaneoplastic anti-GAD LE, discussing the therapeutic management and highlighting the role of neuropsychological assessment. The patient underwent functional and structural brain studies and was investigated longitudinally over a 6-year period with a battery of neuropsychological tests that were designed to document her intellectual function and verbal and visual memory. The patient suffered from refractory temporal-impaired awareness seizures and memory impairment that was mediated by autoimmune nonparaneoplastic LE and comorbid autoimmune disorders (ie, Hashimoto thyroiditis and vitiligo). Neuroimaging studies demonstrated hyperintensities in the medial temporal lobes bilaterally on T2WI MRI sequences. Serial EEGs showed bitemporal intermittent delta activity as well as epileptiform discharges. Tumor blood markers and onconeural antibodies were negative. Immunological screening revealed extremely high GAD-Abs titers in both serum and CSF, as well as the presence of CSF oligoclonal bands. Neuropsychological testing revealed anterograde amnesia with relative preservation of more remote, premorbid memories. The patient underwent first-line immunotherapy followed by immunosuppressive maintenance treatment that led to a reduction of seizures, EEG improvement, and a significant decline in GAD-Abs titers. Neuropsychological evaluations at 5 months, 1 year, and 6 years posttreatment demonstrated improvement, particularly in recent memory and everyday functionality. In this case of anti-GAD LE, the long-term seizure reduction and the improvement of neuropsychological deficits were most likely related to the immunotherapy.
Assuntos
Encefalite Límbica , Adulto , Autoanticorpos , Doenças Autoimunes , Feminino , Seguimentos , Glutamato Descarboxilase , Humanos , Imunoterapia/métodos , Encefalite Límbica/complicações , Encefalite Límbica/terapia , Imageamento por Ressonância Magnética/métodos , Convulsões/complicações , Convulsões/diagnóstico por imagem , Convulsões/terapiaRESUMO
West Nile virus (WNV) is a mosquito-borne RNA flavivirus which caused several epidemics worldwide. The year 2018 was a WNV record year for Europe, including Greece, with earlier and longer transmission season with higher than the previous number of cases. It has been proposed that some simple biochemical markers may be helpful for the recognition of WNV neuroinvasive disease, its differential from other neurological infectious diseases and prognosis. We describe four cases that suffered from WNV meningitis and/or encephalitis hospitalized in 2018 in a tertiary hospital in Thessaloniki, Greece, and investigate the importance of simple biomarkers for the recognition of WNV etiology.
Assuntos
Encefalite Viral/diagnóstico , Meningite Viral/diagnóstico , Febre do Nilo Ocidental/complicações , Febre do Nilo Ocidental/diagnóstico , Fatores Etários , Idoso , Biomarcadores , Feminino , Grécia , Humanos , Masculino , Pessoa de Meia-Idade , Vigilância da População , Fatores Sexuais , Centros de Atenção Terciária , Vírus do Nilo OcidentalRESUMO
BACKGROUND: To the best of our knowledgedd, there is currently no case in the literature reporting the comorbidity of Wilson's and Creutzfeldt-Jakob disease (CJD), linked through copper. CASE PRESENTATION: A 44-year-old male with a history of inherited Wilson's disease (hepatolenticular degeneration), which manifested as mild liver injury and psychiatric symptoms, was admitted to our department due to speech and cognitive disturbances. Upon his admission, he had motor aphasia as well as psychomotor retardation with an otherwise normal neurological examination. Laboratory tests, including liver enzymes, copper and serum ammonia were all within normal range. The brain MRI showed increased T2 signal in the caudate nuclei, attributed to copper deposition in the context of Wilson's disease. In the electroencephalogram, periodic sharp discharges were eminent, initially unilateral and then generalized. The positive 14-3-3 protein in the cerebrospinal fluid (CSF) and the new brain MRI, that demonstrated elevated DWI signal not only in the basal ganglia but also in parts of the cerebral cortex (cortical ribbon sign), all supportive of a possible CJD diagnosis. The detection of PrPSc in the patient's CSF, using the RT-QuIC method, which has a 99.4-100% specificity for CJD, made the diagnosis of CJD highly probable. CONCLUSION: This is the first report of Wilson's and Creutzfeldt-Jakob diseases co-morbidity in the literature, which could evoke a possible role of copper in the pathogenesis of CJD.
Assuntos
Cobre/toxicidade , Síndrome de Creutzfeldt-Jakob/diagnóstico por imagem , Síndrome de Creutzfeldt-Jakob/fisiopatologia , Degeneração Hepatolenticular/fisiopatologia , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Comorbidade , Síndrome de Creutzfeldt-Jakob/líquido cefalorraquidiano , Eletroencefalografia , Degeneração Hepatolenticular/complicações , Humanos , Imageamento por Ressonância Magnética , MasculinoRESUMO
Theory of Mind (ToM) is a critical component of social cognition, and thus, its impairment may adversely affect social functioning and quality of life. Recent evidence has suggested that it is impaired in epilepsy. What is not clear, however, is whether it is related to particular types of epilepsy or other factors. We undertook the present study to explore ToM in patients with focal versus those with generalized epilepsy, the particular pattern of ToM deficits, and the potential influence of antiepileptic medication load. Our sample included 149 adults: 79 patients with epilepsy (34 with generalized epilepsy and 45 with focal epilepsy) and 70 healthy controls. Theory of Mind tasks included a) comprehension of hinting, b) comprehension of sarcasm and metaphor, c) comprehension of false beliefs and deception, d) recognition of faux pas, and e) a visual ToM task in cartoon form. We found significant ToM impairment in the group with focal epilepsy relative to the performance of both the healthy group and the group with generalized epilepsy on all tasks, with the exception of faux pas, on which the group with generalized epilepsy also performed more poorly than the healthy group. Additionally, early age at seizure onset, but not antiepileptic drug (AED) load, was associated with ToM performance. Our findings suggest that focal temporal and frontal lobe, but not generalized, epilepsies were associated with impaired ToM. This may reflect the neuroanatomical abnormalities in the relevant neuronal networks and may have implications for differential cognitive-behavioral interventions based on epilepsy type.
Assuntos
Epilepsias Parciais/diagnóstico por imagem , Epilepsias Parciais/psicologia , Epilepsia Generalizada/diagnóstico por imagem , Epilepsia Generalizada/psicologia , Teoria da Mente/fisiologia , Adulto , Transtornos Cognitivos/diagnóstico por imagem , Transtornos Cognitivos/fisiopatologia , Transtornos Cognitivos/psicologia , Compreensão/fisiologia , Epilepsias Parciais/fisiopatologia , Epilepsia Generalizada/fisiopatologia , Feminino , Lobo Frontal/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Qualidade de Vida/psicologia , Convulsões/fisiopatologia , Convulsões/psicologia , Comportamento Social , Adulto JovemRESUMO
BACKGROUND: Neuroleptic malignant syndrome (NMS) is a rare life-threatening disorder resulting from treatment with neuroleptic agents and other drugs that act as dopamine antagonists. NMS most often occurs shortly after the initiation, dose increase or withdrawal of the offending agent, but can rarely occur after long-term treatment at stable doses. Immediate discontinuation of the causative agent (or re-administration if the cause is the withdrawal of neuroleptic therapy) along with supportive therapy to maintain cardiorespiratory stability and to reduce fever are the cornerstone of the management of NMS. Additional 'specific' treatments include dantrolene, bromocriptine and amantadine, but their role in the management of NMS is controversial. CASE STUDY: This study reports the case of NMS associated with long-term treatment with olanzapine at a stable dose. Administration of dantrolene was well-tolerated and resulted in prompt resolution of NMS symptoms.
Assuntos
Benzodiazepinas/administração & dosagem , Benzodiazepinas/efeitos adversos , Dantroleno/uso terapêutico , Síndrome Maligna Neuroléptica/tratamento farmacológico , Síndrome Maligna Neuroléptica/etiologia , Idoso de 80 Anos ou mais , Feminino , Humanos , OlanzapinaRESUMO
Objective. To determine if there is any correlation between the electroencephalographic and neuroimaging findings in patients with Transient Global Amnesia (TGA). Methods: We retrospectively reviewed files of the First Department of Neurology of AHEPA University Hospital, including patients with a clinical diagnosis of TGA. Only patients who had the characteristic high signal in the temporal lobes in the DWI MRI and those who underwent electroencephalographic recording (EEG) were selected. Results: Out of 28 patients, 8 were selected. We found that 6 out of 8 patients (75%) who had imaging findings in DWI, in at least one medial temporal lobe, also had had intermittent slow theta waves on the electroencephalographic recording. Of these 6 patients, 3 (50%) had bilateral EEG findings, 2 patients (33,3%) only had findings on the left hemisphere and 1 (17%) had on the right hemisphere. 3 out of 6 patients (50%) had electroencephalographic dominance on the left, while 2 out of the 6 (33%) had on the right. In 2 patients with imaging findings in DWI no anomalies were demonstrated on EEG. In 3 out of 8 patients, both MRI and EEG findings correlated on the same side, while 1 patient had opposite findings, depending on which hemisphere the EEG anomalies dominated. Conclusions: There is no absolute matching between the DWI MRI and EEG findings in patients with the clinical diagnosis of TGA. However, there is some degree of correlation, when we focus on the focal dominance of the EEG anomalies, although not statistically significant.
Assuntos
Amnésia Global Transitória , Humanos , Amnésia Global Transitória/diagnóstico , Estudos Retrospectivos , Eletroencefalografia/métodos , Imageamento por Ressonância Magnética , Neuroimagem , HipocampoRESUMO
BACKGROUND: Epileptic patients frequently encounter cognitive impairment. Functions that are mostly affected involve memory, attention, and executive function; however, this is mainly dependent on the location of the epileptic activity. The aim of the present study is to assess cognitive functions in MRI-negative epilepsy patients by means of neurophysiological and neuropsychological measures, as well as study the concept of transient cognitive impairment in patients with epileptiform discharges during EEG acquisition. METHODS: The patients were enrolled from an outpatient Epilepsy/Clinical Neurophysiology clinic over a time period of 6 months. The study sample comprised 20 MRI-negative epilepsy patients (mean age ± standard deviation (SD), 30.3 ± 12.56 years; age range, 16-60 years; average disease duration, 13.95 years) and 10 age-matched controls (mean age ± SD, 24.22 ± 15.39 years), who were also education-matched (p > 0.05). Patients with epileptogenic lesions were excluded from the study. Informed consent was obtained from all subjects involved in the study. Auditory ERPs and the cognitive screening tool EpiTrack were administered to all subjects. RESULTS: Latencies of P300 and slow waves were prolonged in patients compared to controls (p < 0.05). The ASM load and patients' performance in the EpiTrack maze subtest were the most significant predictors of P300 latency. A decline in the memory, attention, and speed of information processing was observed in patients with cryptogenic epilepsy compared to age-matched controls, as reflected by P300 latency and EpiTrack scores.
RESUMO
Generalized spike wave discharges (GSWDs) are the typical electroencephalographic findings of Idiopathic Generalized Epilepsies (IGEs). These discharges are either interictal or ictal and recent evidence suggests differences in their pathogenesis. The aim of this study is to investigate, through functional connectivity analysis, the pre-interictal network state in IGEs, which precedes the formation of the interictal GSWDs. A high-density electroencephalogram (HD-EEG) was recorded in twenty-one patients with IGEs, and cortical connectivity was analyzed based on lagged coherence and individual anatomy. Graph theory analysis was used to estimate network features, assessed using the characteristic path length and clustering coefficient. The functional connectivity analysis identified two distinct networks during the pre-interictal state. These networks exhibited reversed connectivity attributes, reflecting synchronized activity at 3-4 Hz (delta2), and desynchronized activity at 8-10.5 Hz (alpha1). The delta2 network exhibited a statistically significant (p < 0.001) decrease in characteristic path length and an increase in the mean clustering coefficient. In contrast, the alpha1 network showed opposite trends in these features. The nodes influencing this state were primarily localized in the default mode network (DMN), dorsal attention network (DAN), visual network (VIS), and thalami. In conclusion, the coupling of two networks defined the pre-interictal state in IGEs. This state might be considered as a favorable condition for the generation of interictal GSWDs.
RESUMO
Alpha-dystroglycanopathies such as Walker Warburg syndrome represent an important subgroup of the muscular dystrophies that have been related to defective O-mannosylation of alpha-dystroglycan. In many patients, the underlying genetic etiology remains unsolved. Isolated muscular dystrophy has not been described in the congenital disorders of glycosylation (CDG) caused by N-linked protein glycosylation defects. Here, we present a genetic N-glycosylation disorder with muscular dystrophy in the group of CDG type I. Extensive biochemical investigations revealed a strongly reduced dolichol-phosphate-mannose (Dol-P-Man) synthase activity. Sequencing of the three DPM subunits and complementation of DPM3-deficient CHO2.38 cells showed a pathogenic p.L85S missense mutation in the strongly conserved coiled-coil domain of DPM3 that tethers catalytic DPM1 to the ER membrane. Cotransfection experiments in CHO cells showed a reduced binding capacity of DPM3(L85S) for DPM1. Investigation of the four Dol-P-Man-dependent glycosylation pathways in the ER revealed strongly reduced O-mannosylation of alpha-dystroglycan in a muscle biopsy, thereby explaining the clinical phenotype of muscular dystrophy. This mild Dol-P-Man biosynthesis defect due to DPM3 mutations is a cause for alpha-dystroglycanopathy, thereby bridging the congenital disorders of glycosylation with the dystroglycanopathies.
Assuntos
Dolicol Monofosfato Manose/metabolismo , Manosiltransferases/genética , Proteínas de Membrana/genética , Distrofias Musculares/genética , Distrofias Musculares/metabolismo , Distroglicanas/metabolismo , Feminino , Glicosilação , HumanosRESUMO
Many contradictory theories regarding epileptogenesis in idiopathic generalized epilepsy have been proposed. This study aims to define the network that takes part in the formation of the spike-wave discharges in patients with generalized tonic-clonic seizures alone (GTCSa) and elucidate the network characteristics. Furthermore, we intend to define the most influential brain areas and clarify the connectivity pattern among them. The data were collected from 23 patients with GTCSa utilizing low-density electroencephalogram (EEG). The source localization of generalized spike-wave discharges (GSWDs) was conducted using the Standardized low-resolution brain electromagnetic tomography (sLORETA) methodology. Cortical connectivity was calculated utilizing the imaginary part of coherence. The network characteristics were investigated through small-world propensity and the integrated value of influence (IVI). Source localization analysis estimated that most sources of GSWDs were in the superior frontal gyrus and anterior cingulate. Graph theory analysis revealed that epileptic sources created a network that tended to be regularized during generalized spike-wave activity. The IVI analysis concluded that the most influential nodes were the left insular gyrus and the left inferior parietal gyrus at 3 and 4 Hz, respectively. In conclusion, some nodes acted mainly as generators of GSWDs and others as influential ones across the whole network.
RESUMO
PURPOSE OF REVIEW: Drug-resistant epilepsy represents around one-quarter of epilepsies worldwide. Although ketogenic diets (KD) have been used for refractory epilepsy since 1921, the past 15 years have witnessed an explosion of KD use in the management of epilepsy. We aimed to review evidence from randomized controlled trials (RCTs) regarding the efficacy and safety of KD in drug-resistant epilepsy in children and adolescents. RECENT FINDINGS: A literature search was performed in the Pubmed, Cohrane, Scopus, ClinicalTrials.gov, and Google Scholar databases. Predefined criteria were implemented regarding data extraction and study quality. Data were extracted from 14 RCTs in 1114 children and adolescents aged from 6 months to 18 years. Primary outcome was seizure reduction after the intervention. In 6 out of the 14 studies, there was a statistical significant seizure reduction by > 50% in the KD-treated group compared with the control group over a follow-up of 3-4 months. Secondary outcomes were adverse events, seizure severity, quality of life, and behavior. Gastrointestinal symptoms were the most frequent adverse events. Serious adverse events were rare. We conclude that the KD is an effective treatment for drug-resistant epilepsy in children and adolescents. Accordingly, RCTs investigating long-term impact, cognitive and behavioral effects, and cost-effectiveness are much anticipated.
Assuntos
Dieta Cetogênica , Epilepsia Resistente a Medicamentos , Epilepsia , Adolescente , Criança , Dieta Cetogênica/efeitos adversos , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Epilepsia/tratamento farmacológico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , ConvulsõesRESUMO
A high-fat and low-carbohydrate diet was administered as a complementary and alternative therapy to a 54-year-old man suffering from non-small-cell lung cancer (NSCLC) with brain metastasis. Three months after the cessation of chemotherapy and radiotherapy, a ketogenic diet (KD) was initiated. This approach was an attempt to stabilize the disease progression after chemotherapy and radiotherapy. Computed tomography following radiation and chemotherapy showed a reduction in the right frontal lobe lesion from 5.5 cm × 6.2 cm to 4 cm × 2.7 cm, while the mass in the upper-right lung lobe reduced from 6.0 cm × 3.0 cm to 2.0 × 1.8 cm. Two years after KD initiation and without any other therapeutic intervention, the right frontal lobe lesion calcified and decreased in size to 1.9 cm × 1.0 cm, while the size of the lung mass further decreased to 1.7 cm × 1.0 cm. The size of the brain and lung lesion remained stable after nine years of KD therapy. However, dyslipidemia developed after this time which led to the discontinuation of the diet. No tumor relapse or health issues occurred for two years after the discontinuation of the diet. This case report indicates that the inclusion of ketogenic metabolic therapy following radiation and chemotherapy is associated with better clinical and survival outcomes for our patient with metastatic NSCLC.
RESUMO
BACKGROUND: Rapidly progressive dementias (RPDs) are dementias that progress subacutely over a time period of weeks to months. Primary Sjögren's syndrome (pSS) is an autoimmune disease that can affect any organ system and may present with a wide range of clinical features that may mimic a plethora of medical conditions and, in rare cases, may manifest as RPD. We describe a unique case of pSS, in which rapidly progressive dementia (RPD) was the first disease manifestation, and the patient's radiological and electroencephalogram findings were compatible with Creutzfeldt- Jakob disease (CJD). CASE PRESENTATION: Here, we report a 58-year-old woman who presented with cognitive impairment rapidly deteriorating over the last 6 months prior to admission. Brain MRI and EEG were indicative of CJD. However, CSF 14-3-3 and tau/phospho tau ratio were within normal limits and therefore alternative diagnoses were considered. Blood tests were significant for positive antinuclear antibodies, anti-ENA, and anti-SSA and a lip biopsy was consistent with pSS. The patient was started on intravenous steroids followed by oral prednisone taper, which prevented further deterioration. CONCLUSION: This rare case expands the spectrum of neurological manifestations in pSS and highlights the importance of considering pSS in the differential diagnosis of RPDs in order to avoid misdiagnosis and provide appropriate treatment in a timely fashion.
Assuntos
Síndrome de Creutzfeldt-Jakob , Síndrome de Sjogren , Feminino , Humanos , Pessoa de Meia-Idade , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Síndrome de Sjogren/complicações , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/patologia , Prednisona , Anticorpos Antinucleares , Síndrome de Creutzfeldt-Jakob/diagnóstico , Síndrome de Creutzfeldt-Jakob/patologia , Síndrome de Creutzfeldt-Jakob/psicologiaRESUMO
Mutations in the FOLR1 gene, encoding for the folate alpha receptor (FRa), represent a rare recessive genetic cause of cerebral folate deficiency (CFD), a potentially reversible neurometabolic condition. Patients typically present with developmental delay, seizures, abnormal movements, and delayed myelination. We hereby expand the phenotypic and genotypic spectrum of the disease with the report of the first two Greek siblings that were found compound heterozygous for one known FOLR1 gene mutation (p.Cys65Trp) and a mutation (p.Trp143Arg) that has not yet been reported in the literature (class 3 variant according to ASHG classification). A distinguishing feature of the older sibling is the manifestation of drug-resistant epileptic spasms beyond infancy. These had a relatively good response to a ketogenic diet, as an additional treatment to topiramate and valproate. A further clinical improvement was observed when folinic acid was combined with the above treatment. While a response to folinic acid is well established in the disorder, the efficacy of its combination with the ketogenic diet needs further evaluation, but we suggest considering it early in the course of drug resistant epilepsy in the setting of CFD. The younger sibling was diagnosed and treated with folinic acid at an early-symptomatic stage. Both patients had moderately low age-related CSF 5-methyltetrahydrofolate levels at diagnosis with the older sibling (that was already treated at base line collection) averaging 19 nmol/L (normal range: 44-122 nmol/L) and the younger one 49 nmol/L (normal range 63-122 nmol/L). These levels were restored to normal limits after folinic supplementation.
RESUMO
We describe a cohort of 10 unrelated Greek patients (4 females, 6 males; median age 6.5â¯years, range 2-18â¯years) with heterogeneous epilepsy syndromes with a genetic basis. In these patients, causative genetic variants, including two novel ones, were identified in 9 known epilepsy-related genes through whole exome sequencing. A patient with glycine encephalopathy was a compound heterozygote for the p.Arg222Cys and the p.Ser77Leu AMT variant. A patient affected with Lafora disease carried the homozygous p.Arg171His EPM2A variant. A de novo heterozygous variant in the GABRG2 gene (p.Pro282Thr) was found in one patient and a pathogenic variant in the GRIN2B gene (p.Gly820Val) in another patient. Infantile-onset lactic acidosis with seizures was associated with the p.Arg446Ter PDHX gene variant in one patient. In two additional epilepsy patients, the p.Ala1662Val and the novel non-sense p.Phe1330Ter SCN1A gene variants were found. Finally, in 3 patients we observed a novel heterozygous missense variant in SCN2A (p.Ala1874Thr), a heterozygous splice site variant in SLC2A1 (c.517-2A>G), as a cause of Glut1 deficiency syndrome, and a pathogenic variant in STXBP1 (p.Arg292Leu), respectively. In half of our cases (patients with variants in the GRIN2B, SCN1A, SCN2A and SLC2A1 genes), a genetic cause with potential management implications was identified.
RESUMO
PURPOSE: The aim of this retrospective service evaluation was to determine the nature, frequency and clinical value of seizure occurrence during extraoperative direct cortical stimulation for functional mapping in patients undergoing invasive recordings (icEEG) for epilepsy surgery workup. METHODS: We reviewed 145 sequential cases of patients with refractory focal epilepsy who underwent intracranial electrode implantation and extraoperative direct cortical stimulation (CS) for functional mapping. CS intended for mapping can elicit as a by-product electrical or electroclinical events, such as afterdischarges, subclinical EEG seizures, and stimulation-induced seizures (SIS). SIS may have habitual or non-habitual semiology (as defined by comparison to the patient's spontaneous events). RESULTS: In our cohort, electrical (subclinical EEG seizures) or electroclinical events, (SIS) were recorded in 34.5% (50/145) patients during CS. SIS occurred in 23.4% (34/145) of all patients, of which over half were habitual SIS (SIShab). In most cases the location of contacts eliciting habitual SIS originated from the same location as the spontaneous ictal onset zone in icEEG. Of those with SIS hab undergoing surgery (n = 13), seizure freedom was achieved in 61.5%, and of those with SISNH undergoing surgery (n = 10), 40% became seizure free (ns). CONCLUSIONS: Electroclinical SIS occur in about a quarter of CS for functional mapping; SIS are habitual in the majority of cases, and where elicited, SIS in icEEG could be an additional diagnostic tool to localize the seizure onset zone. However, a significant minority of stimulations lead to non-habitual SIS.
Assuntos
Epilepsia Resistente a Medicamentos , Epilepsias Parciais , Epilepsia , Epilepsia Resistente a Medicamentos/cirurgia , Eletroencefalografia , Epilepsias Parciais/cirurgia , Humanos , Estudos Retrospectivos , Convulsões/epidemiologia , Convulsões/etiologiaRESUMO
Inherited muscle disorders are caused by pathogenic changes in numerous genes. Herein, we aimed to investigate the etiology of muscle disease in 24 consecutive Greek patients with myopathy suspected to be genetic in origin, based on clinical presentation and laboratory and electrophysiological findings and absence of known acquired causes of myopathy. Of these, 16 patients (8 females, median 24 years-old, range 7 to 67 years-old) were diagnosed by Whole Exome Sequencing as suffering from a specific type of inherited muscle disorder. Specifically, we have identified causative variants in 6 limb-girdle muscular dystrophy genes (6 patients; ANO5, CAPN3, DYSF, ISPD, LAMA2, SGCA), 3 metabolic myopathy genes (4 patients; CPT2, ETFDH, GAA), 1 congenital myotonia gene (1 patient; CLCN1), 1 mitochondrial myopathy gene (1 patient; MT-TE) and 3 other myopathy-associated genes (4 patients; CAV3, LMNA, MYOT). In 6 additional family members affected by myopathy, we reached genetic diagnosis following identification of a causative variant in an index patient. In our patients, genetic diagnosis ended a lengthy diagnostic process and, in the case of Multiple acyl-CoA dehydrogenase deficiency and Pompe's disease, it enabled specific treatment to be initiated. These results further expand the genotypic and phenotypic spectrum of inherited myopathies.