The neurological disorders and stroke represent the last century’s medical challenge. Despite increasing number of elderly people and the subsequent increase of neurological diseases, in socalled industrialized countries, we have no efficacious strategy to fight this plague.

Probably, the more effective method to take on this challenge may be a rigorous prevention and principle risk factors (e.g. high-pressure, stress, obesity, smoke of tobacco and alcohol) elimination. On the other hand, further scientific research in this field could be very useful. This kind of research should be based on the use of animal models to improve current understanding of the pathophysiological features of these diseases and may yield important information on how to improve analysis of the “efficacy” of some possible molecules.

As the expansion of global aging population with improved lifespan and loaded social burden, the incidence of neurological disorders including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD) and Amyotrophic Lateral Sclerosis (ALS) presents a continuous climbing trend [1]. All of these neurological disorders afflicting health status and quality of life for elderly and increasing medical burden to their family and society are highly associated with protein quality control, because damaged, mis-folded or aggregated proteins can cause the proteotoxic stress for cell functional impairment and the intracytoplasmic deposition of aggregate-prone proteins or dysfunctional mitochondria in neurons with limited treatment strategies [2].

Autophagy is a cellular self-consumption process characterized by sequestration of bulk cytoplasm, long-lived proteins and damaged cellular organelles in double membrane vesicles called autophagosomes, which are delivered to lysosomes for the degradation [3,4]. Protein quality control via autophagy is particularly important for the timely removal of aggregated forms of pathogenic proteins in neurodegenerative diseases, including tau in AD, α-synuclein in PD and polyQ-Htt in HD [5,6]. It is also a powerful and selective degradation process for dysfunctional mitochondria in neurons for maintaining mitochondrial homeostasis. A decline in autophagic function is a common trait of the aging process

The neonatal astrocytes used to be considered a population of stage specific, proliferating immature astrocytes. Over the course of brain maturation, the newly generated astrocytesundergo extensive changes in gene expression, form spatially exclusive domains, connect through gap junctions into a syncytial network, and interact with and envelop blood vessels as part of the blood brain barrier [1-8]. Over the past two decades, increasing evidence shows that the very same “immature” astrocytes are the sculptors of synaptogenesisand facilitators of myelination in the CNS [8-10].

Background: Osteogenesis Imperfecta (OI) is a rare inherited collagen disease of variable severity. Our patient was diagnosed with OI prior to aneurysmal Subarachnoid Hemorrhage (aSAH) occurrence. To our knowledge, this is the first case report of an OI patient with SAH associated vasospasm treated with milrinone.

Case Presentation: A 35 year old female - known for OI - was brought to the Neuro-critical care unit after being intubated for generalized tonic-clonic seizure. A CT/CTA of the brain revealed acute aSAH due to basilar artery aneurysmal rupture, with early hydrocephalus. An External Ventricular Drain (EVD) was installed and the aneurysm was coiled the next day. Two days later her Glasgow Comma Scale (GCS) was back to 15/15. Ten Days post aSAH she became obtunded, with right arm weakness. Transcranial Doppler confirmed the diagnosis of vasospasm. She received IV Mi-lrinone and regained her level of consciousness and power. Her modified Rankin Score (mRS) was 1 at time of discharge and 0 three months later. To our knowledge, this is the first case report of OI treated (successfully) using IV milrinone for cerebral vasospasm after aSAH.

Conclusion: Cerebral vasospasm after aSAH has been known to occur in OI. Here we present a patient with OI who developed vasospasm related deficit that responded well to IV Milrinone, with good outcome based on mRS

Autosomal Recessive Primary Microcephaly (MCPH) is one of the most common hereditary neurological disorders in Saudi Arabia. Frequent consanguineous unions, due to isolated tribal set ups and large family sizes, is considered the primary reason for this high prevalence. In our study we ascertained a consanguineous family living in the South-Western region of the Kingdom. The patients were characterized by primary microcephaly, moderate intellectual disability and developmental delays. For genetic analysis we performed SNP array Based Comparative Genome Hybridization (aCGH) and analyzed the data for homozygosity mapping alongside Whole Exome Sequencing (WES). Three putative causal variants in regions of extended homozygosity on chromosome 1q31, chromosome 5p13.2 and chromosome 5p13.3 were identified: respectively, a nonsense variant in the ASPM gene (NM_018136; c.8903G>A; p.Trp2968*); a missense variant in SPEF2 (NM_024867; c.1262G>A; p.Arg421His); and a missense variant in PDZD2 (NM_178140; c.2153C>A; p.Thr718Asn) were found potential candidates for the disease phenotype in this family. Sanger sequencing determined that the variants in SPEF2 and PDZD2 did not co-segregate with the disease phenotype. However, the nonsense variant in ASPM does co-segregate with disease in this family. Our study concludes WES as a successful molecular diagnostic tool in this highly inbred population.