- Advances in autoimmune myasthenia gravis management. [Journal Article]
- ERExpert Rev Neurother 2018 Jun 22
- Myasthenia gravis (MG) is an autoimmune neuromuscular disorder with no cure and conventional treatments limited by significant adverse effects and variable benefit. In the last decade, therapeutic de...
Myasthenia gravis (MG) is an autoimmune neuromuscular disorder with no cure and conventional treatments limited by significant adverse effects and variable benefit. In the last decade, therapeutic development has expanded based on improved understanding of autoimmunity and financial incentives for drug development in rare disease. Clinical subtypes exist based on age, gender, thymic pathology, autoantibody profile, and other poorly defined factors, such as genetics, complicate development of specific therapies. Areas covered. Clinical presentation and pathology vary considerably among patients with some having weakness limited to the ocular muscles and others having profound generalized weakness leading to respiratory insufficiency. MG is an antibody-mediated disorder dependent on autoreactive B cells which require T cell support. Treatments focus on elimination of circulating autoantibodies or inhibition of effector mechanisms by a broad spectrum of approaches from plasmapheresis to B cell elimination to complement inhibition. Expert Commentary. Standard therapies and those under development are disease modifying and not curative. As a rare disease, clinical trials are challenged in patient recruitment. The great interest in development of treatments specific for MG is welcome, but decisions will need to be made to focus on those that offer significant benefits to patients.
- Antiviral activity of maraviroc plus mirtazapine in a low-risk HIV-negative patient with progressive multifocal leukoencephalopathy. [Journal Article]
- IMInfez Med 2018 Jun 01; 26(2):160-163
- A case of progressive multifocal leukoencephalopathy (PML) is described in an HIV-negative patient with mixed connective-tissue disease (MCTD) on a minimally immunosuppressive treatment with hydroxyc...
A case of progressive multifocal leukoencephalopathy (PML) is described in an HIV-negative patient with mixed connective-tissue disease (MCTD) on a minimally immunosuppressive treatment with hydroxychloroquine. The patient presented with right-sided weakness, episodes of disorientation and loss of short-term memory and of vision in her right eye. PML was diagnosed by JCV DNA on cerebrospinal fluid and radiological criteria. She was treated with off-label maraviroc and mirtazapine but died two months after hospital admission, despite a surprising decrease in the viral load of cerebrospinal fluid three weeks after starting therapy. Prompt diagnosis and antiviral treatment of PML even in low-risk patients are warranted. Future studies are required to define the therapeutic role of maraviroc (MVC) and mirtazapine in this setting.
- Validation of the new AJCC eighth edition of the TNM classification for breast cancer with a single-center breast cancer cohort. [Journal Article]
- BCBreast Cancer Res Treat 2018 Jun 21
- CONCLUSIONS: The AJCC 8th edition clinical staging system provides a good prognostic value and addresses the weakness of the AJCC 7th edition, which uses only anatomical pathologic staging.
- TNNT1 nemaline myopathy: Natural history and therapeutic frontier. [Journal Article]
- HMHum Mol Genet 2018 Jun 20
- We describe the natural history of 'Amish' nemaline myopathy (ANM), an infantile-onset, lethal disease linked to a pathogenic c.505G>T nonsense mutation of TNNT1, which encodes the slow fiber isoform...
We describe the natural history of 'Amish' nemaline myopathy (ANM), an infantile-onset, lethal disease linked to a pathogenic c.505G>T nonsense mutation of TNNT1, which encodes the slow fiber isoform of troponin T (TNNT1; a.k.a TnT). The TNNT1 c.505G>T allele has a carrier frequency of 6.5% within Old Order Amish settlements of North America. We collected natural history data for 106 ANM patients born between 1923 and 2017. Over the last two decades, mean age of molecular diagnosis was 16 ± 27 days. TNNT1 c.505G>T homozygotes were normal weight at birth but failed to thrive by age 9 months. Presenting neonatal signs were axial hypotonia, hip and shoulder stiffness, and tremors, followed by progressive muscle weakness, atrophy, and contractures. Affected children developed thoracic rigidity, pectus carinatum, and restrictive lung disease during infancy, and all succumbed to respiratory failure by 6 years of age (median survival 18 months, range 0.2-66 months). Muscle histology from two affected children showed marked fiber size variation due to both type 1 myofiber smallness (hypotrophy) and type 2 fiber hypertrophy, with evidence of nemaline rods, myofibrillar disarray, and vacuolar pathology in both fiber types. The truncated slow TNNT1 (TnT) fragment (p.Glu180Ter) was undetectable in ANM muscle, reflecting its rapid proteolysis and clearance from sarcoplasm. Similar functional and histological phenotypes were observed in other human cohorts and two transgenic murine models (Tnnt1-/- and Tnnt1 c.505G>T). These findings have implications for emerging molecular therapies, including the suitably of TNNT1 gene replacement for newborns with ANM or other TNNT1-associated myopathies.
- Post Vaccination Guillain Barre Syndrome: A Case Report. [Journal Article]
- CCureus 2018 Apr 20; 10(4):e2511
- Guillain-Barre syndrome is a rare but fatal autoimmune disease. The exact cause of Guillain-Barre syndrome is still unknown. The most common known etiology of Guillain-Barre syndrome is infectious di...
Guillain-Barre syndrome is a rare but fatal autoimmune disease. The exact cause of Guillain-Barre syndrome is still unknown. The most common known etiology of Guillain-Barre syndrome is infectious disease notably caused by Campylobacter jejuni. A very small fraction of people can develop Guillain-Barre syndrome due to vaccines and vaccinations like a meningococcal vaccine, poliovirus vaccine, influenza vaccine, and rabies vaccine. Of all these, rabies is fatal invariably. It can be preventable if diagnosed early and post-exposure treatment is followed according to the World Health Organization guidelines. Older formulations of rabies vaccines are cultured in the neural tissues and have been found to have an increased risk of Guillain-Barre syndrome. Although less immunogenic older formulations of rabies vaccines are more commonly used in Asian and South American countries due to their cost-effective nature. There is little to no data available on the incidence of Guillain-Barre syndrome due to vaccinations in Pakistan. Most of the cases of Guillain-Barre syndrome due to vaccination are either undiagnosed or misdiagnosed. In this case report, we are presenting a case of vaccine-associated Guillain-Barre syndrome due to neural tissue anti-rabies vaccine in a young girl, who presented with lower limb weakness, inability to pass urine and abdominal pain.
- Familial Normokalemic Periodic Paralysis Associated With Mutation in the SCN4A p.M1592V. [Journal Article]
- FNFront Neurol 2018; 9:430
- Periodic paralysis (PP) is an uncommon inherited disorder causing recurrent episodes of muscle weakness, with an incidence of 0.001%. Normokalemic periodic paralysis (NormoKPP) as the rarest subtype ...
Periodic paralysis (PP) is an uncommon inherited disorder causing recurrent episodes of muscle weakness, with an incidence of 0.001%. Normokalemic periodic paralysis (NormoKPP) as the rarest subtype of PP contains both familial and sporadic. Familial NormoKPP caused by the p.M1592V mutation of the skeletal muscle sodium channel alpha subunit (SCN4A) gene is rarely reported. Only three pedigrees of NormoKPP related to mutations in the SCN4A p.M1592V have been previously reported. We herein presented a family case of NormoKPP associated with the SCN4A p.M1592V mutation, in which respiratory muscle paralysis occurred in the proband while not in his children. Moreover, we conducted a thorough literature review. To our knowledge, this is the first report of respiratory muscle paralysis as a symptom of NormoKPP associated with mutation in the SCN4A p.M1592V.
- Spontaneous onset pseudophakic malignant glaucoma secondary to zonular weakness and cilio-lenticular block. [Journal Article]
- OJOman J Ophthalmol 2018 May-Aug; 11(2):178-180
- Malignant glaucoma (MG), also known as aqueous misdirection and cilio-vitreo-lenticular block, is an infrequent cause of secondary angle closure glaucoma. Despite conventional treatment, it often has...
Malignant glaucoma (MG), also known as aqueous misdirection and cilio-vitreo-lenticular block, is an infrequent cause of secondary angle closure glaucoma. Despite conventional treatment, it often has a poor visual outcome. It is recognized clinically by raised intraocular pressure associated with shallowing of the peripheral and central anterior chamber in the presence of a patent peripheral iridotomy/iridectomy. Despite being known to occur after a variety of surgical procedures, it most commonly presents following filtration surgery in hypermetropic eyes with angle closure glaucoma. It can present within a range of postsurgical latencies, ranging from 1 day to many months. We describe a case of pseudophakic MG that was unusual in that it presented spontaneously many years following cataract surgery. We postulate the etiology of our spontaneous onset pseudophakic MG was the anterior subluxation of the large diameter intraocular lens secondary to zonular weakness.
- Macrophage Activation Syndrome (MAS) in a Recently Released Prisoner with Systemic Lupus Erythematosus (SLE). [Journal Article]
- AJAm J Case Rep 2018 Jun 22; 19:734-738
- CONCLUSIONS: Many of the symptoms, signs, and laboratory findings of SLE overlap with those of MAS, and concomitant presence of both of these disease poses unique diagnostic challenges as well as extreme risk to the patient. A robust set of criteria for identifying MAS in the setting of a confounding underlying rheumatological illness does not exist in the adult population; this case illustrates the approach taken by our team to come to this diagnosis.
- [Hyperperfusion after Revascularization for Quasi-moyamoya Disease Associated with Graves' Disease:A Case Report]. [Journal Article]
- NSNo Shinkei Geka 2018; 46(6):501-508
- We report a case of cerebral hyperperfusion syndrome accompanied by postoperative intracerebral hemorrhage following blood flow reconstruction for quasi-moyamoya disease associated with Graves' disea...
We report a case of cerebral hyperperfusion syndrome accompanied by postoperative intracerebral hemorrhage following blood flow reconstruction for quasi-moyamoya disease associated with Graves' disease that had caused cerebral infarctions. A 44-year-old woman presented with repeated sensory impairment of the fingers on the left hand and weakness of the right lower limb and multiple cerebral infarctions developed in the bilateral frontal lobes. Magnetic resonance angiography and cerebral angiography suggested quasi-moyamoya disease. On hospitalization, untreated Graves' disease was identified and treated first. Revascularization was performed in the region of the right middle cerebral artery, where reduced cerebral blood flow and depressed vascular reactivity persisted half a year after treatment of Graves' disease, but postoperative cerebral hemorrhage appeared after 5 days due to hyperperfusion syndrome around the anastomotic site. Lethal hyperperfusion syndrome following revascularization of quasi-moyamoya disease associated with Graves' disease appears very rare and has not been reported previously.
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- Does encountering the facial nerve during surgical management of mandibular condylar process fractures increase the risk of facial nerve weakness? A systematic review and meta-regression analysis. [Review]
- JCJ Craniomaxillofac Surg 2018 Apr 17
- CONCLUSIONS: This meta-analysis demonstrated that manipulation of the facial nerve during different surgical approaches causes different incidences of facial nerve injury. The choice of surgical approach for a given fracture should take this into consideration.