Epilepsy

Another Genetic Clue To Autism: Opposite Malfunctions Have Same Result

Source: 
Medical News Today
Date Published: 
November 25, 2011
Abstract: 

In most cases, autism is caused by a combination of genetic factors, but some cases, such as Fragile X syndrome, can be traced to a variation in a single gene that causes overproduction of proteins in brain synapses. Now a new study led by the same MIT neuroscientist who made that discovery, finds that tuberous sclerosis is caused by a malfunction at the opposite end of the spectrum: underproduction of the synaptic proteins.

Treatment-resistant epilepsy common in idiopathic autism

Source: 
Eurek Alert
Date Published: 
April 19. 2011
Abstract: 

A new study found that treatment-resistant epilepsy (TRE) is common in idiopathic autism. Early age at the onset of seizures and delayed global development were associated with a higher frequency of resistance to antiepileptic drugs (AEDs). Full findings appear online in Epilepsia, a journal published by Wiley-Blackwell on behalf of the International League Against Epilepsy (ILAE).

Common Genetic Cause of Autism and Epilepsy Discovered

Source: 
Science Daily
Date Published: 
April 8, 2011
Abstract: 

Led by the neurologist Dr. Patrick Cossette, the research team found a severe mutation of the synapsin gene (SYN1) in all members of a large French-Canadian family suffering from epilepsy, including individuals also suffering from autism.

Language Dysfunction in Children May Be Due to Epilectic Brain Activity

Source: 
Science Daily
Date Published: 
April 23, 2010
Abstract: 

Epileptic activity in the brain can affect language development in children, and EEG registrations should therefore be carried out more frequently on children with severe language impairment to identify more readily those who may need medical treatment, reveals a thesis from the Sahlgrenska Academy at the University of Gothenburg.

First Direct Recording Made of Mirror Neurons in Human Brain

Source: 
Science Daily
Date Published: 
April 13, 2010
Abstract: 

Neuroscientists believe this "mirroring" is the mechanism by which we can "read" the minds of others and empathize with them. It's how we "feel" someone's pain, how we discern a grimace from a grin, a smirk from a smile. Problem was, there was no proof that mirror neurons existed -- only suspicion and indirect evidence. Dr. Itzhak Fried, a UCLA professor of neurosurgery and of psychiatry and biobehavioral sciences, Roy Mukamel, a postdoctoral fellow in Fried's lab, and their colleagues have for the first time made a direct recording of mirror neurons in the human brain.

It's suspected that dysfunction of these mirror cells might be involved in disorders such as autism, where the clinical signs can include difficulties with verbal and nonverbal communication, imitation and having empathy for others. So gaining a better understanding of the mirror neuron system might help devise strategies for treatment of this disorder.

Tuberous Sclerosis Complex Proteins Control Axon Formation

Source: 
Genes Development, Choi, DiNardo, et al
Date Published: 
2008
Year Published: 
2008

Axon formation is fundamental for brain development and function. TSC1 and TSC2 are two genes, mutations in which cause tuberous sclerosis complex (TSC), a disease characterized by tumor predisposition and neurological abnormalities including epilepsy, mental retardation, and autism. Here we show that Tsc1 and Tsc2 have critical functions in mammalian axon formation and growth. Overexpression of Tsc1/Tsc2 suppresses axon formation, whereas a lack of Tsc1 or Tsc2 function induces ectopic axons in vitro and in the mouse brain. Tsc2 is phosphorylated and inhibited in the axon but not dendrites. Inactivation of Tsc1/Tsc2 promotes axonal growth, at least in part, via up-regulation of neuronal polarity SAD kinase, which is also elevated in cortical tubers of a TSC patient. Our results reveal key roles of TSC1/TSC2 in neuronal polarity, suggest a common pathway regulating polarization/growth in neurons and cell size in other tissues, and have implications for the understanding of the pathogenesis of TSC and associated neurological disorders and for axonal regeneration.

Reversal of Learning Deficits in a Ts2+/- Mouse Model of Tuberous Sclerosis

Source: 
Nature Medicine, Ehninger, Han, et al
Date Published: 
2008
Year Published: 
2008

Tuberous sclerosis is a single-gene disorder caused by heterozygous mutations in the TSC1 (9q34) or TSC2 (16p13.3) gene and is frequently associated with mental retardation, autism and epilepsy. Even individuals with tuberous sclerosis and a normal intelligence quotient (approximately 50%) are commonly affected with specific neuropsychological problems, including long-term and working memory deficits. Here we report that mice with a heterozygous, inactivating mutation in the Tsc2 gene (Tsc2(+/-) mice) show deficits in learning and memory. Cognitive deficits in Tsc2(+/-) mice emerged in the absence of neuropathology and seizures, demonstrating that other disease mechanisms are involved. We show that hyperactive hippocampal mammalian target of rapamycin (mTOR) signaling led to abnormal long-term potentiation in the CA1 region of the hippocampus and consequently to deficits in hippocampal-dependent learning. These deficits included impairments in two spatial learning tasks and in contextual discrimination. Notably, we show that a brief treatment with the mTOR inhibitor rapamycin in adult mice rescues not only the synaptic plasticity, but also the behavioral deficits in this animal model of tuberous sclerosis. The results presented here reveal a biological basis for some of the cognitive deficits associated with tuberous sclerosis, and they show that treatment with mTOR antagonists ameliorates cognitive dysfunction in a mouse model of this disorder.

Mortality and Causes of Death in Autism Spectrum Disorders: An Update

Source: 
Autism, Mouridsen, Bronnum-Hansen, et al
Date Published: 
2008

This study compared mortality among Danish citizens with autism spectrum disorders (ASDs) with that of the general population. A clinical cohort of 341 Danish individuals with variants of ASD, previously followed over the period 1960-93, now on average 43 years of age, were updated with respect to mortality and causes of death. Standardized mortality ratios (SMRs) were calculated for various times after diagnosis. In all, 26 persons with ASD had died, whereas the expected number of deaths was 13.5. Thus the mortality risk among those with ASD was nearly twice that of the general population. The SMR was particularly high in females. The excess mortality risk has remained unchanged since our first study in 1993. Eight of the 26 deaths were associated with epilepsy and four died from epilepsy. Future staff education should focus on better managing of the complex relationships between ASD and physical illness to prevent avoidable deaths.