Case Report: A Novel Genetic Mutation Causes Idiopathic Infantile Arterial Calcification in Preterm Infants

Idiopathic infantile arterial calcification (IIAC), also known as generalized arterial calcification of infancy (GACI), is a heritable ectopic mineralization disorder that results in diffuse arterial calcifications and or stenosis, which are attributed to mutations in the ENPP1 gene. In this case study, we report the development of IIAC in a 2-month-old male preterm infant. The patient presented with severe hypertension and seizures, which revealed diffused calcifications and c.130C > T and c.1112A > T mutations in the ENPP1 gene. With biphosphonate, antihypertensive, and control epilepsy therapy, his blood pressure was maintained at 110–120/50–60 mmHg. Intellectual motor development retardation was anticipated in this patient. To the best of our knowledge, this is the first case in which a novel c.130C > T mutation in the ENPP1 gene has been identified, and the administration of bisphosphonates to patients with IIAC has been assessed.

Certain risk factors for the development of cognitive impairment in persons with epilepsy and new therapeutic options

Epilepsy is a common chronic neurological disease. The problems of people with epilepsy go well beyond epileptic seizures. Comorbidities in epilepsy are very common and often cause more problems to the patients than the seizures themselves. Although seizures are the most prominent clinical presentation of epilepsy, people with epilepsy are exposed to risk of not only seizures, but also of many health problems. Both children and adults with epilepsy often complain of memory impairment. It is commonly believed that cognitive dysfunction in epilepsy is multifactorial. The components that deteriorate cognitive functions include active seizures and especially generalized tonic-clonic seizures, traumatic brain injuries, structural epilepsy, and drug therapy. Cognitive dysfunction is very often present as far back as during the onset of epilepsy. The cognitive dysfunction detected in patients with epilepsy depend on the localization of the epileptic focus, the frequency and type of epileptic seizures, and changes in the interictal electroencephalogram. Seizures can be controlled with antiepileptic drugs in most patients with epilepsy. Therapy of cognitive dysfunction in patients with epilepsy presents significant difficulties, as there is no evidence of the efficacy of various drugs in cognitive disorders. The article presents a new Russian antiepileptic drug based on phenosanic acid as part of combination therapy in patients with partial epileptic seizures with or without secondary generalization, which can improve cognitive functions in patients with epilepsy.

The Utility of Delta-9-Tetrahydrocannibinol Therapy in a Multiple Sclerosis Patient with a Neoplastic Brain Lesion

Multiple sclerosis (MS) can sometimes cause uncommon pseudotumoural lesions that produce atypical symptoms, such as motor epileptic seizures which are often pharmacoresistant. In these cases, accurate diagnosis is essential for correct therapy, even if unconventional. We present the case of a brain tumour in a 40-year-old relapsing-remitting MS patient who presented with pharmacoresistant seizures which eventually responded to nabiximols. After various therapeutic approaches, delta-9-tetrahydrocannabinol therapy was introduced with good results. Spasticity improved, pain decreased and we observed a reduction in the number of daily seizures. It is possible that delta-9-tetrahydrocannabinol can enhance the efficacy of anti-epilepsy therapy.

Societal return on investment may greatly exceed financial return on investment in neurotechnology-based therapies: A case study in epilepsy therapy development

Background: This research study is an economic analysis of a neurotechnology-based translational research and development venture focused on the development of a therapy for patients with epilepsy. In the conceptualization, planning, financing, and execution of neurotechnology ventures, many factors come into play in determining value and ability to secure financing at each stage of the venture. Conventionally, these have included factors that determine the return on investment for the stakeholders of the venture, most notably the investors and the team members, the former investing hard earned capital, and the latter investing significant portions of their professional careers. For a variety of reasons, the positive impact on society is often not quantified and taken into consideration. Methods: To address this, a new term is defined and assessed at a first approximation level using an index technology. The metric is termed the societal return on investment (sROI). Results: Among chronic conditions, neurological disease is virtually unique in the magnitude of economic devastation that it can inflict on a person and a family. Because the device costs do not reflect this value that is lost and subject to restoration, these are missing from this important calculation. The index project is the development of a seizure advisory system, which cost $71.2 million to develop and conduct a First-In-Man (FIM) study (NCT01043406) and which was estimated to require $50 million to complete a pivotal study. Conclusion: Despite the immense costs required to develop, test, and commercialize such a system, the direct and indirect economic costs imposed by uncontrolled seizures are sufficiently staggering that a sROI becomes positive after only 400 patients have been successfully treated and returned to work.

Drug Resistance in Epilepsy: Which Prospect to Tame its Stubbornness?

Epilepsy is a major health problem, it being among the most common chronic neurologic pathologies. Its basic therapy is via anti-seizure drugs (ASDs), of which nearly two dozen are currently available for symptomatic treatment of epileptic seizures. But, notwithstanding the increasing ASD options, about one-third of epileptic patients remain drug-refractory, and this fraction did not diminish over decades. This paper reviews the subject of drug resistance in epilepsy (DRE), in view of exploring the prospect to overcome its persistence. The survey of various hypotheses about DRE origin and mechanisms notices that any of them alone does not fully account the DRE, their multitude deriving from the lack of solution to this bad medical need. The non-pharmacological (neurosurgical, brain stimulation, focal treatments and dietary) approaches of drug-intractable epilepsy are also surveyed, with the sober conclusion that, in a predictable future, the mainstay of epilepsy therapy will likely remain the drugs. The vast multiplicity of molecular changes associated with DRE suggests that its pharmacological resolution might arise only from integrative, systemic approaches, beyond the reductionist single-target paradigm that dominated the ASD discovery, in the last several decades. A conceivable lessening of DRE might be brought about by precision (personalized) medicine, assisted by complex systems biology description of individual epileptic pathology. In a longer run, the emergent network pharmacology might led to genuine innovative multi-potent antiepileptic drugs, able to treat distinct subpopulations of current refractory patients.