Low Frequency Ultrasound With Injection of NMO-IgG and Complement Produces Lesions Different From Experimental Autoimmune Encephalomyelitis Mice

Neuromyelitis optica spectrum disorder (NMOSD), a relapsing autoimmune disease of the central nervous system, mainly targets the optic nerve and spinal cord. To date, all attempts at the establishment of NMOSD animal models have been based on neuromyelitis optica immunoglobulin G antibody (NMO-IgG) and mimic the disease in part. To solve this problem, we developed a rodent model by opening the blood-brain barrier (BBB) with low frequency ultrasound, followed by injection of NMO-IgG from NMOSD patients and complement to mice suffering pre-existing neuroinflammation produced by experimental autoimmune encephalomyelitis (EAE). In this study, we showed that ultrasound with NMO-IgG and complement caused marked inflammation and demyelination of both spinal cords and optic nerves compared to blank control group, as well as glial fibrillary acidic protein (GFAP) and aquaporin-4 (AQP4) loss of spinal cords and optic nerves compared to EAE mice and EAE mice with only BBB opening. In addition, magnetic resonance imaging (MRI) revealed optic neuritis with spinal cord lesions. We further demonstrated eye segregation defects in the dorsal lateral geniculate nucleus (dLGN) of these NMOSD mice.

Neuromyelitis optica with brain stem involvement in a middle-aged Ethiopian woman: a case report and review of literature

Introduction Neuromyelitis optica is a demyelinating disease of the central nervous system that predominantly affects the optic nerves and spinal cord. In neuromyelitis optica, white blood cells and antibodies primarily attack the optic nerves and the spinal cord, but may also attack the brain. Brainstem manifestation has been described recently. So far, neuromyelitis optica is very rare in Ethiopia and there were only two case reports, but this is the first case report of neuromyelitis optica with brainstem involvement. Case presentation A 47-year-old Addis Ababa woman presented to Saint Paul’s Hospital Millennium Medical College with a history of visual loss of 7 years and bilateral lower limb weakness of 4 days duration. She had bilateral oculomotor nerve palsy. Her past medical history showed systemic hypertension for 18 years and dyslipidemia for 1 year. The objective evaluation of the patient revealed right optic nerve atrophy suggesting optic neuritis and flaccid paraplegia with sensory level at the fourth thoracic vertebra. Diagnostic work-up using electromyography and spinal magnetic resonance imaging revealed demyelinating anterior visual pathway dysfunction and signs of extensive cervicothoracic transverse myelitis from the third cervical to lower thoracic vertebrae, respectively. Then a diagnosis of neuromyelitis optica was established. After treatment with high-dose systemic steroid followed by azathioprine, the patient was stable for several months with significant improvement of vision and lower-extremity weakness with no relapse of symptoms. Conclusion The case described here is a rare inflammatory demyelinating disorder of the central nervous system occurring in East Africa. It reminds clinicians to suspect neuromyelitis optica in a patient who presented with unexplained recurrent optic neuritis to make a timely diagnosis and prevention of permanent neuronal damage. Neuromyelitis optica can also be associated with oculomotor nerve involvement.

The Retino-Hypothalamic Ultrastructural Changes in Traumatic Optic Neuropathy

Aim: To study the retino-hypothalamic ultrastructural changes in traumatic optic neuropathy’s pathogenesis and treatment. Methods: Four groups of mature rabbits were included in this experiment, 30 in each group, 120 in total. The traumatic crush to the optic nerves was reproduced by surgical clips to 90 mature rabbits. The first group (I) included intact/control animals, the second (II) included animals with traumatic optic neuropathy and two other traumatized groups (III and IV) who were given two different doses of treatment. The animals in group III were given infusions of Methylprednisolone 30mg/kg/day for three days. The group IV animals received infusion of 15mg/kg/ day of Methylprednisolone for 3 days in combination with phosphine electric stimulation (PES), starting from the third until the 13th day of the experiment. The electrical pulse which was used on the affected side of the animal was 800 mА and 300 mА on the opposite side. The morphological analysis of the retina and suprachiasmatic nucleus of the hypothalamus of all the four groups of animals included electron microscopy of the semi-thin and ultrathin sections. This analysis was performed a month following the initial injury while the animals were removed from the experiment. The levels of cortisol and adrenocorticotropic hormone (ACTH) in the blood of all experimental animals was tested up to one month following the injury to the optic nerves. Results: We found that trauma to the orbital part of the optic nerve causes collocative necrosis of ganglion cells and swelling of the nerve fiber layer of the ipsilateral retina. In addition, such traumatic damage causes structural changes in the suprachiasmatic nucleus of the hypothalamus. Combined treatment of methylprednisolone with phosphine electro stimulation in traumatized rabbits reduced the thickness of the retina, reduced the cytokaryometric indices and the regeneration processes of bipolar and ganglion cells of the retina. Histopathologically we found an increased number of neurosecretory granules in the suprachiasmatic nucleus of the hypothalamus. ACTH levels in the blood of the group III rabbits were found to be lower, while the cortisol levels higher, and these hormone levels in the IV group rabbits were quite similar to those of the group which was not treated. Conclusion: The combined treatment of traumatic optic neuropathy in rabbits with phosphine electrostimulation and methylprednisolone can be considered a useful treatment, having a beneficial neuroprotective effect.

Shear wave elastography in optic neuritis: diagnostic accuracy of the optic nerve and adjacent fat tissue values

Introduction: In this study, we attempt to determine the diagnostic performance of shear wave elastography of the optic nerve and adjacent fat tissue in patients with optic neuritis. Methods: The study included a patient group consisting of 72 eyes of 36 patients who were diagnosed with unilateral optic neuritis, and an age-matched control group of 36 eyes of 18 healthy subjects. The patient group consisted of 25 multiple sclerosis patients and 11 recurrent isolated optic neuritis patients. The mean shear wave elastography values of the optic nerves and intraorbital fat tissue adjacent optic nerves were recorded using m/s and kPa as units. ROC curve analysis was performed, and the diagnostic accuracy of shear wave elastography values was determined. Results: The mean shear wave elastography values of the optic nerves with neuritis (2.49 ± 0.41 m/s and 17.56 ± 4.42 kPa) were significantly higher than the values of the contralateral normal optic nerves (1.71 ± 0.32 m/s and 9.02 ± 2.34 kPa) (p = 0.006 and p = 0.004, respectively) in the optic neuritis group. The mean shear wave elastography values of intraorbital fat tissue adjacent optic nerves with neuritis (1.87 ± 0.32 m/s and 9.65 ± 1.12 kPa) were significantly higher than the values of the contralateral normal side (1.47 ± 0.27 m/s and 6.78 ± 1.14 kPa) (p = 0.025 and p = 0.022, respectively) in the optic neuritis group. ROC curve analysis showed a high diagnostic accuracy for determining optic neuritis with shear wave elastography values of the optic nerves (AUC 0.955 [95% CI, 0.933–0.978] in m/s and AUC 0.967 [95% CI, 0.940–0.985] in kPa). Conclusions: Shear wave elastography may be an important alternative diagnostic tool in the diagnosis of optic neuritis.

An Experimental Model of Neuromyelitis Optica Spectrum Disorder–Optic Neuritis: Insights Into Disease Mechanisms

Background: Optic neuritis (ON) is a common inflammatory optic neuropathy, which often occurs in neuromyelitis optica spectrum disease (NMOSD). An experimental model of NMOSD-ON may provide insight into disease mechanisms.Objective: To examine the pathogenicity of autoantibodies targeting the astrocyte water channel aquaporin-4 [aquaporin-4 (AQP4)-immunoglobulin G (AQP4-IgG)] in the optic nerve.Materials and Methods: Purified IgG from an AQP4-IgG-positive NMOSD-ON patient was together with human complement (C) given to wild-type (WT) and type I interferon (IFN) receptor-deficient mice (IFNAR1-KO) as two consecutive intrathecal injections into cerebrospinal fluid via cisterna magna. The optic nerves were isolated, embedded in paraffin, cut for histological examination, and scored semi-quantitatively in a blinded fashion. In addition, optic nerves were processed to determine selected gene expression by quantitative real-time PCR.Results: Intrathecal injection of AQP4-IgG+C induced astrocyte pathology in the optic nerve with loss of staining for AQP4 and glial fibrillary acidic protein (GFAP), deposition of C, and demyelination, as well as upregulation of gene expression for interferon regulatory factor-7 (IRF7) and CXCL10. Such pathology was not seen in IFNAR1-KO mice nor in control mice.Conclusion: We describe induction of ON in an animal model for NMOSD and show a requirement for type I IFN signaling in the disease process.

Comparison of a Hybrid IMRT/VMAT technique with non-coplanar VMAT and non-coplanar IMRT for unresectable olfactory neuroblastoma using the RayStation treatment planning system—EUD, NTCP and planning study

The purpose of this study was to compare hybrid intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (Hybrid IMRT/VMAT), with non-coplanar (nc) IMRT and nc-VMAT treatment plans for unresectable olfactory neuroblastoma (ONB). Hybrid IMRT/VMAT, nc-IMRT and nc-VMAT plans were optimized for 12 patients with modified Kadish C stage ONB. Dose prescription was 65 Gy in 26 fractions. Dose–volume histogram parameters, conformation number (CN), homogeneity index (HI), integral dose and monitor units (MUs) delivered per fraction were assessed. Equivalent uniform dose (EUD) and normal tissue complication probability (NTCP) based on the EUD model (NTCPLogit) and the Lyman–Kutcher–Burman model (NTCPLKB) were also evaluated. We found that the Hybrid IMRT/VMAT plan significantly improved the CN for clinical target volume (CTV) and planning treatment volume (PTV) compared with the nc-VMAT plan. In general, sparing of organs at risk (OARs) is similar with the three techniques, although the Hybrid IMRT/VMAT plan resulted in a significantly reduced Dmax to contralateral (C/L) optic nerve compared with the nc-IMRT plan. The Hybrid IMRT/VMAT plan significantly reduce EUD to the ipsilateral (I/L) and C/L optic nerve in comparison with the nc-IMRT plan and nc-VMAT plan, but the difference in NTCP between the three technique was <1%. We concluded that the Hybrid IMRT/VMAT technique can offer improvement in terms of target conformity and EUD for optic nerves, while achieving equal or better OAR sparing compared with nc-IMRT and nc-VMAT, and can be a viable radiation technique for treating unresectable ONB. However, the clinical benefit of these small differences in dosimetric data, EUD and NTCP of optic nerves may be minimal.