Neuro-ophthalmic manifestations of Susac syndrome.

PURPOSE OF REVIEW: This review discusses general features and organ-specific presentations of Susac syndrome as well as diagnosis and treatment. RECENT FINDINGS: Latest literature regarding demographics, new diagnostic modalities such as optical coherence tomography and treatment options for Susac syndrome are discussed in detail in this review, summarizing the most recent updated information. SUMMARY: Susac syndrome is a rare, underdiagnosed, and often misdiagnosed disease that can lead to severe complications such as deafness, vision loss, dementia, and death. It involves the central nervous system and may mimic other neurological and neuro-ophthalmological diseases.

Broadening the phenotype of LRRK1 mutations - Features of malignant osteopetrosis and optic nerve atrophy with intrafamilial variable expressivity.

Osteosclerotic metaphyseal dysplasia is a rare disorder which features osteosclerosis involving long bones, vertebrae, ribs, clavicles and the iliac crests. Additional features which have variably been reported include developmental delay, short stature, hypotonia and seizures. The disease is caused by pathogenic variants in the LRRK1 gene, and inherited in an autosomal recessive manner. We report three siblings (ages 14 years, 11.5 years and 0.9 years), born to consanguineous parents of Arab-Muslim descent, harboring a homozygous pathogenic variant in the LRRK1 gene (Chr15:101068759 AGGGGCT>A, c.5965_5970del TGGGGC, p.Trp1989Gly1990del). The patients displayed variable degrees of skeletal dysplasia, with the oldest sibling most severely affected, and the youngest infant with minor skeletal involvement. Two of the siblings exhibited normal neurological development, while the youngest sibling exhibited global developmental delay. None of the siblings had seizures; however, two of them exhibited nystagmus. Optic nerve involvement has not previously been reported to be part of the clinical spectrum of this disease. The degree of optic nerve involvement did not correlate with the degree of skeletal involvement. This indicates both intra-familial variable expressivity along with a broadening of the spectrum of LRRK1-associated disease. These findings warrant reconsideration of therapeutic strategies, including the possibility of hematopoietic stem cell transplantation (HSCT) as is performed in cases of malignant and intermediate forms of osteopetrosis.

CT definition of the surgical apex in the orbit.

The orbital apex is an undefined but well understood concept of Orbital Surgeons. We sought to determine the surgical apex area specifically where the volume ratio decreases significantly impacting on the optic nerve. A retrospective analysis using PACS program processing, measured the right retrobulbar space volume changes in 100 randomly selected cases without orbital pathology where CT was performed for non-ophthalmic indications. Volume of the retrobulbar space was measured between two recognizable landmarks. The first landmark being the point of exit of the optic nerve from the eye and the second landmark the optic nerve's point of exit from the orbit. The measured length between these two points was divided into five equal segments, V1-V5. The volumes of all 5 segments were compared and the most significant area of volume depletion was established. The mean numeric value of measured orbital volumes was compared. A ratio difference of V1/V2 was less than 2, V2/V3 was 2.32 (± 0.27), V3/4 was 3.24 (± 0.39), and V4/V5 was 5.67 (± 1.66). The most remarkable difference in ratio was between V4 and V5 (mean 5.67 ± 1.66 with p < .0001). The V3 segment (the posterior 3/5 of the retrobulbar space volume) is the location where decrease in orbital volume impacts, and measured ratios are statistically significant. We defined the surgical apex as the posterior 3/5 of the retro-bulbar orbital space. It is consequently the area of higher risk for optic nerve compression. This definition could be routinely utilized by ophthalmologists and neuroradiologists when evaluating masses affecting the orbit.

Rodent Models of Optic Neuritis.

Optic neuritis (ON) is an inflammatory attack of the optic nerve that leads to visual disability. It is the most common optic neuropathy affecting healthy young adults, most commonly women aged 20-45 years. It can be idiopathic and monophasic or as part of a neurologic disease such as multiple sclerosis with recurrence and cumulative damage. Currently, there is no therapy to repair the damage from optic neuritis. Animal models are an essential tool for the understanding of the pathogenesis of optic neuritis and for the development of potential treatment strategies. Experimental autoimmune encephalomyelitis (EAE) is the most commonly used experimental rodent model for human autoimmune inflammatory demyelinating diseases of the central nervous system (CNS). In this review, we discuss the latest rodent models regarding optic neuritis, focusing on EAE model, and on its recent achievements and developments.