Intense Immunosuppression Followed by Autologous Stem Cell Transplantation in Severe Multiple Sclerosis Cases
Richard K. Burt, Alberto M. Marmont in Stem Cell Therapy for Autoimmune Disease, 2019
Case 3 is a 40 year old female who reported numbness in the lower limbs followed by visual loss in the right eye occurring three years earlier. Visual evoked potentials (VEPs) were delayed on both sides and MRI of the brain was normal. After a few months, she experienced loss of leg strength. Again MRI was negative, but cerebro-spinal fluid (CSF) examination showed oligoclonal bands in the CSF and serum, with additional bands in the CSF. The patient improved and remained in almost normal condition for 2 years, at which time she experienced a severe tetraparesis. MRI of the brain and spinal cord showed multiple T2 lesions areas, some of which enhanced after a single dose of Gd. After 1 month, paraparesis worsened and visual disturbances recurred. A diagnosis of neuromyelitis optica was established. The patient was treated with CY (1.5 grams IV) and then with plasma exchange, without any significant improvement. At that time, EDSS was 6.5. After 4 months, her neurological condition rapidly worsened, reaching an almost complete paraplegia. When the patient’s EDSS was 8 it was decided to treat her with intense immunosuppression and ASCT, similarly to the other previously reported cases. The patient signed an informed consent. This patient was not included in the frequent MRI study because EDSS was higher than the upper limit established in the protocol.
The nervous system and the eye
C. Simon Herrington in Muir's Textbook of Pathology, 2020
Familial aggregation of multiple sclerosis and twin studies, which show a higher level of concordance among monozygotic than dizygotic twins, suggest that genetic factors may be important. MS is not inherited in a simple genetic fashion, but patients have over-representation of certain histocompatability antigens, suggesting that genetic variation in control of the immune response may be important. The variation in the prevalence of MS with latitude is unexplained: there is a gradient in each hemisphere with high disease rates at high latitudes, e.g. in north-east Scotland (1 in 500 of the population) and virtual absence at the equator. Environmental factors, particularly in childhood, appear to be important. People who migrate from one area to another after the age of 15 years retain the incidence of their childhood locality. Before the Second World War, MS was unknown in the isolated communities of the Faroe islands but, with increased contact with the rest of the world, it has a high prevalence of MS. Although these studies suggest an infective aetiology, none of the numerous candidate organisms studied has been consistently implicated. Oligoclonal bands of IgG in CSF indicate that IgG is produced by plasma cells derived from a small number of B-lymphocyte clones. These observations may indicate a reaction to an infective agent or an autoimmune response to a neural component (e.g. myelin). Demyelinating antibodies have been detected in the serum of patients with MS, but these are not specific because they are found in patients with other disorders. However, neuromyelitis optica (Devic's disease) affects mainly the optic nerves and spinal cord and used to be considered a variant of MS, but is now known to be an autoimmune disease with antibodies to the astrocyte protein Aquaporin 4.
Approach to “Visual Loss”
Vivek Lal in A Clinical Approach to Neuro-Ophthalmic Disorders, 2023
Vascular episodes involving posterior circulation may be recurrent. Bilateral optic neuritis also has recurrences, especially in patients of neuromyelitis optica. STEP 4: Is the visual loss progressive?
A case of neuromyelitis optica spectrum disorder with coexisting systemic lupus erythematosus
Published in Journal of Community Hospital Internal Medicine Perspectives, 2021
Vikram Sangani, Mytri Pokal, Mamtha Balla, Ganesh Prasad Merugu, Sreedhar Adapa, Srikanth Naramala, Venu Madhav Konala
Neuromyelitis optica is a rare relapsing, inflammatory demyelinating disease of the central nervous system primarily affecting optic nerves and spinal cord. The Aquaporin-4 (AQP4) antibody and complement pathway play an important role in the pathogenesis of NMOSD. NMO-IgG selectively binds to the aquaporin-4 water channel located in astrocyte foot processes at the blood-brain barrier [7] and leads to direct injury to the central nervous system as a result of astrocyte injury by antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) [8,9]. As per International consensus, diagnosis can be made based on the presence of one core clinical characteristics as in Table 5, NMO IgG antibodies with the exclusion of alternative diagnosis [10]. In the absence of NMO IgG antibodies, two core clinical criteria along with exclusion of alternate diagnosis or additional MRI findings will suffice.
Retinal Findings on OCT in Systemic Conditions
Published in Seminars in Ophthalmology, 2018
Preeti Patil Chhablani, Vikas Ambiya, Akshay G. Nair, Sailaja Bondalapati, Jay Chhablani
Spectral domain OCT imaging has demonstrated microcystic changes in the inner nuclear layer in certain patients with optic atrophy. Such changes have been described in patients with neuromyelitis optica-related optic neuritis.108 Recent studies have shown the presence of similar microcystic changes in the inner nuclear layer also in cases of Leber’s hereditary optic atrophy, dominant optic atrophy, compressive optic neuropathy, glaucomatous optic atrophy, and hydrocephalus.109-111 Damage or destruction of the axons forming a part of the optic nerve may ultimately result in trans-synaptic degeneration, which may manifest as microcystic changes in the inner layers of the retina where the bodies of these cells may lie. This theory is supported by findings of experiments conducted in primates by Van Buren in 1963 which showed the presence of cavitory degeneration in the inner nuclear layer after optic nerve crush injury.112
Pallid Disc Oedema in a Young Patient: Clinical and Diagnostic Challenge
Published in Neuro-Ophthalmology, 2022
Liana Dedina, Mark M. Hassall, Shilpanjali Jesudason, Sumu Simon
This patient with with end-stage kidney disease and past extensive immunosuppression exposure had presented with painless and rapidly progressing vision loss. He was investigated for infective, inflammatory, infiltrative and vasculitic aetiologies. Of note, an immunological work up had been performed earlier in the year for non-specific joint symptoms, and did not identify any significant abnormalities. A blood work-up showed a normocytic anaemia with a haemoglobin level of 86 g/L and a mild neutrophilia. The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were elevated at 72 mm/hr and 14.9 mg/L, respectively (note the caveat, ESR is less relevant in a dialysed patient with renal anaemia on erythropoietin). Anti-neuromyelitis optica antibodies were not detected. Rheumatoid factor, anti-cyclic citrullinated peptide (anti-CCP), extractable nuclear antigen (ENA) antibody test, syphilis and tuberculosis screening were negative. A lumbar puncture did not detect cryptococcus, Toxoplasma gondii, herpes simplex viruses, parechovirus, Varicella zoster, Neis-seria meningitidis or Strepto- coccus pneumoniae in the cerebrospinal fluid. A chest radiograph was unremarkable. Non-contrast magnetic resonance imaging (MRI) of the head and orbits did not show any optic nerve compression or infiltration, nor evidence of demyelination. Intravenous methylprednisolone therapy at 1 g/day was given for three days.
Related Knowledge Centers
- Aquaporin
- Autoantibody
- Inflammation
- Myelitis
- Optic Nerve
- Optic Neuritis
- Spinal Cord
- Immunoglobulin G
- Aquaporin-4
- Anti-Aqp4 Disease