Seizure-triggered Takotsubo syndrome rarely causes SUDEP.

Since almost 20 y it is known that seizures may trigger Takotsubo syndrome (TTS). Since then it has been repeatedly proposed that TTS could be the cause of sudden unexpected death in epilepsy (SUDEP). A review of the so far reported cases of seizure-triggered TTS was carried out to see how often seizure-triggered TTS is fatal.

Faulty cardiac repolarization reserve in alternating hemiplegia of childhood broadens the phenotype.

Alternating hemiplegia of childhood is a rare disorder caused by de novo mutations in the ATP1A3 gene, expressed in neurons and cardiomyocytes. As affected individuals may survive into adulthood, we use the term 'alternating hemiplegia'. The disorder is characterized by early-onset, recurrent, often alternating, hemiplegic episodes; seizures and non-paroxysmal neurological features also occur.

Increased pCREB expression and the spontaneous epileptiform activity in a BCNU-treated rat model of cortical dysplasia.

Objective: Cortical dysplasias (CDs) represent a wide range of cortical abnormalities that closely correlate with intractable epilepsy. Rats prenatally exposed to 1-3-bis-chloroethyl-nitrosurea (BCNU) represent an injury-based model that reproduces many histopathologic features of human CD. Previous studies reported in vivo hyperexcitability in this model, but in vivo epileptogenicity has not been confirmed.

Mutations of C19orf12, coding for a transmembrane glycine zipper containing mitochondrial protein, cause mis-localization of the protein, inability to respond to oxidative stress and increased mitochondrial Ca²⁺.

Mutations in C19orf12 have been identified in patients affected by Neurodegeneration with Brain Iron Accumulation (NBIA), a clinical entity characterized by iron accumulation in the basal ganglia. By using western blot analysis with specific antibody and confocal studies, we showed that wild-type C19orf12 protein was not exclusively present in mitochondria, but also in the Endoplasmic Reticulum (ER) and MAM (Mitochondria Associated Membrane), while mutant C19orf12 variants presented a different localization. Moreover, after induction of oxidative stress, a GFP-tagged C19orf12 wild-type protein was able to relocate to the cytosol.

From Grey Scale B-Mode to Elastosonography: Multimodal Ultrasound Imaging in Meningioma Surgery-Pictorial Essay and Literature Review.

The main goal in meningioma surgery is to achieve complete tumor removal, when possible, while improving or preserving patient neurological functions. Intraoperative imaging guidance is one fundamental tool for such achievement. In this regard, intra-operative ultrasound (ioUS) is a reliable solution to obtain real-time information during surgery and it has been applied in many different aspect of neurosurgery.

Modeling human Coenzyme A synthase mutation in yeast reveals altered mitochondrial function, lipid content and iron metabolism.

Mutations in nuclear genes associated with defective coenzyme A biosynthesis have been identified as responsible for some forms of neurodegeneration with brain iron accumulation (NBIA), namely PKAN and CoPAN. PKAN are defined by mutations in , encoding the pantothenate kinase 2 enzyme, that account for about 50% of cases of NBIA, whereas mutations in CoA synthase have been recently reported as the second inborn error of CoA synthesis leading to CoPAN. As reported previously, yeast cells expressing the pathogenic mutation exhibited a temperature-sensitive growth defect in the absence of pantothenate and a reduced CoA content.

Next generation sequencing for systematic assessment of genetics of small-vessel disease and lacunar stroke.

Background: The pathogenesis of cerebral small-vessel disease (SVD) is still incompletely understood, although evidence from family and twin studies supports the hypothesis that genetic factors may contribute to SVD pathogenesis. Identification of genetic susceptibility factors for SVD may improve our knowledge on SVD pathogenesis. SVE-LA (Small Vessel and Lacunar) project is a multicenter prospective Lombardia region study aimed at applying innovative genetic technologies and accurate patient phenotyping to discover the genetic basis of SVD.

7T MRI features in control human hippocampus and hippocampal sclerosis: an ex vivo study with histologic correlations.

Objective: Hippocampal sclerosis (HS) is the major structural brain lesion in patients with temporal lobe epilepsy (TLE). However, its internal anatomic structure remains difficult to recognize at 1.5 or 3 Tesla (T) magnetic resonance imaging (MRI), which allows neither identification of specific pathology patterns nor their proposed value to predict postsurgical outcome, cognitive impairment, or underlying etiologies.

Facing contrast-enhancing gliomas: perfusion MRI in grade III and grade IV gliomas according to tumor area.

Tumoral neoangiogenesis characterizes high grade gliomas. Relative Cerebral Blood Volume (rCBV), calculated with Dynamic Susceptibility Contrast (DSC) Perfusion-Weighted Imaging (PWI), allows for the estimation of vascular density over the tumor bed. The aim of the study was to characterize putative tumoral neoangiogenesis via the study of maximal rCBV with a Region of Interest (ROI) approach in three tumor areas-the contrast-enhancing area, the nonenhancing tumor, and the high perfusion area on CBV map-in patients affected by contrast-enhancing glioma (grades III and IV).

The Mitochondrial Aminoacyl tRNA Synthetases: Genes and Syndromes.

Mitochondrial respiratory chain (RC) disorders are a group of genetically and clinically heterogeneous diseases. This is because protein components of the RC are encoded by both mitochondrial and nuclear genomes and are essential in all cells. In addition, the biogenesis and maintenance of mitochondria, including mitochondrial DNA (mtDNA) replication, transcription, and translation, require nuclear-encoded genes.

Exome sequence reveals mutations in CoA synthase as a cause of neurodegeneration with brain iron accumulation.

Neurodegeneration with brain iron accumulation (NBIA) comprises a clinically and genetically heterogeneous group of disorders with progressive extrapyramidal signs and neurological deterioration, characterized by iron accumulation in the basal ganglia. Exome sequencing revealed the presence of recessive missense mutations in COASY, encoding coenzyme A (CoA) synthase in one NBIA-affected subject. A second unrelated individual carrying mutations in COASY was identified by Sanger sequence analysis.

Pantothenate kinase-associated neurodegeneration: altered mitochondria membrane potential and defective respiration in Pank2 knock-out mouse model.

Neurodegeneration with brain iron accumulation (NBIA) comprises a group of neurodegenerative disorders characterized by high brain content of iron and presence of axonal spheroids. Mutations in the PANK2 gene, which encodes pantothenate kinase 2, underlie an autosomal recessive inborn error of coenzyme A metabolism, called pantothenate kinase-associated neurodegeneration (PKAN). PKAN is characterized by dystonia, dysarthria, rigidity and pigmentary retinal degeneration.

Expression of neural and neurotrophic markers in nucleus pulposus cells isolated from degenerated intervertebral disc.

Intervertebral disc (IVD) degeneration is a common disorder of the lower spine. Since it is caused by loss of cellularity, there is interest in the comprehension of the cellular phenotypes. This study aimed to verify if stem cells isolated from nucleus pulposus of intervertebral discs (NPs-IVD), which may express neurogenic properties, may be implicated in IVD disease.

Microscale oxygraphy reveals OXPHOS impairment in MRC mutant cells.

Given the complexity of the respiratory chain structure, assembly and regulation, the diagnostic workout for the identification of defects of oxidative phosphorylation (OXPHOS) is a major challenge. Spectrophotometric assays, that measure the activity of individual respiratory complexes in tissue and cell homogenates or isolated mitochondria, are highly specific, but their utilization is limited by the availability of sufficient biological material and intrinsic sensitivity. A further limitation is tissue specificity, which usually determines attenuation, or disappearance, in cultured fibroblasts, of defects detected in muscle or liver.

Metabolic consequences of mitochondrial coenzyme A deficiency in patients with PANK2 mutations.

Pantothenate kinase-associated neurodegeneration (PKAN) is a rare, inborn error of metabolism characterized by iron accumulation in the basal ganglia and by the presence of dystonia, dysarthria, and retinal degeneration. Mutations in pantothenate kinase 2 (PANK2), the rate-limiting enzyme in mitochondrial coenzyme A biosynthesis, represent the most common genetic cause of this disorder. How mutations in this core metabolic enzyme give rise to such a broad clinical spectrum of pathology remains a mystery.

Epilepsy in type 1 Chiari malformation.

In patients with Chiari malformation type 1 (CMI), epileptic seizures are occasionally reported both in symptomatic patients candidate to surgery and in patients without symptoms of tonsillar displacement in whom CM1 is often an incidental finding in the diagnostic work up for idiopathic epilepsies. In both groups of patients, the course of epilepsy is almost invariably favorable, with a few seizures easily controlled by treatment. In a subset of CM1 patients, epilepsy occurs in the context of neurodevelopmental disorders that also include mental retardation, autism and somatic dysmorphisms.

Comprehensive care of children with Dravet syndrome.

The comprehensive care of a patient with Dravet syndrome encompasses both the "care" and the "cure" of the patient, and requires cooperation among family, doctors, and several other specialized caregivers to search for the attainment of the best quality of life for the patients and their families. Several issues peculiar to the disease to be faced while dealing with the patient are: (1) SMEI is an "evolving" disease that appears in an otherwise healthy child with symptoms that appear and mutate throughout the course of the disease; (2) the severity of the disease is not fully predictable at onset and appears to be individual-specific; (3) the seizures are invariably drug resistant and seizure freedom is not a realistic goal; and (4) in addition to seizures many other invalidating clinical problems, including cognitive impairment, behavior disorders, and a number of comorbidities characterize the disease course. The comprehensive caring must be physician-guided and patient-centered and implies a multidisciplinary approach to be built around the children and caregivers, who need to be guided through the steps of the diagnosis, treatments, and managements of the various comorbidities.

Cognitive development in children with Dravet syndrome.

Slowing of cognitive skills represents one of the diagnostic criteria of Dravet syndrome. This Italian multicentric study aims at clarifying the roles of epilepsy and/or underlying genetic alteration in determining the cognitive outcome. The study includes infants that were either in follow-up (retrospective study: 26 cases) and newly diagnosed (prospective study: in progress).

Cognitive development in Dravet syndrome: a retrospective, multicenter study of 26 patients.

Purpose: To clarify the role of epilepsy and genetic background in determining the cognitive outcome of patients with Dravet syndrome.

Methods: In this retrospective study, we reviewed the clinical history and cognitive development of 26 patients who had been followed with standardized evaluations since seizure onset. The cognitive outcome was quantified as differential general quotient (dGQ) between ages 12 and 60 months.

How do human cells react to the absence of mitochondrial DNA?

Background: Mitochondrial biogenesis is under the control of two different genetic systems: the nuclear genome (nDNA) and the mitochondrial genome (mtDNA). The mtDNA is a circular genome of 16.6 kb encoding 13 of the approximately 90 subunits that form the respiratory chain, the remaining ones being encoded by the nDNA.

Clinical and molecular features of mitochondrial DNA depletion syndromes.

Mitochondrial DNA depletion syndromes (MDSs) form a group of autosomal recessive disorders characterized by profoundly decreased mitochondrial DNA copy numbers in affected tissues. Three main clinical presentations are known: myopathic, encephalomyopathic and hepatocerebral. The first is associated with mutations in thymidine kinase 2 (TK2) and p53-induced ribonucleotide reductase B subunit (RRM2B); the second with mutations in succinate synthase A (SUCLA2) and B (SUCLG1); the third with mutations in Twinkle (PEO1), pol-gammaA (POLG1), deoxyguanosine kinase (DGUOK) and MPV17 (MPV17).

Identification of novel mutations in five patients with mitochondrial encephalomyopathy.

MELAS, MERRF, LHON and NARP, are well-established mitochondrial syndromes associated with specific point mutations of mitochondrial DNA (mtDNA). However, these recurrent mtDNA mutations account for only a minority of mitochondrial disease cases. To evaluate the impact of novel mtDNA mutations, we performed mtDNA sequence analysis in muscle and other tissues of 240 patients with different mitochondrial neuromuscular syndromes.

Early-onset liver mtDNA depletion and late-onset proteinuric nephropathy in Mpv17 knockout mice.

In humans, MPV17 mutations are responsible for severe mitochondrial depletion syndrome, mainly affecting the liver and the nervous system. To gain insight into physiopathology of MPV17-related disease, we investigated an available Mpv17 knockout animal model. We found severe mtDNA depletion in liver and, albeit to a lesser extent, in skeletal muscle, whereas hardly any depletion was detected in brain and kidney, up to 1 year after birth.

Nodular heterotopia: a neuropathological study of 24 patients undergoing surgery for drug-resistant epilepsy.

Purpose: Despite the availability of detailed electroclinical and imaging data, only a few neuropathological studies of nodular heterotopia have been published. The aim of this study was to describe the neuropathological features of various types of nodular heterotopia obtained from patients undergoing surgery for intractable epilepsy.

Methods: Specimens of heterotopic nodules taken from 24 patients were neuropathologically investigated using routine and immunocytochemical procedures, and the data were compared with magnetic resonance imaging (MRI), electroclinical findings, and surgical outcomes.