Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028738 (nystagmus)
 7,431 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multiple sclerosis (MS) commonly causes eye movement abnormalities that may have a significant impact on patients' disability. Inflammatory demyelinating lesions, especially occurring in the posterior fossa, result in a wide range of disorders, spanning from acquired pendular nystagmus (APN) to internuclear ophthalmoplegia (INO), among the most common. As the control of eye movements is well understood in terms of anatomical substrate and underlying physiological network, studying ocular motor abnormalities in MS provides a unique opportunity to gain insights into mechanisms of disease. Quantitative measurement and modeling of eye movement disorders, such as INO, may lead to a better understanding of common symptoms encountered in MS, such as Uhthoff's phenomenon and fatigue. In turn, the pathophysiology of a range of eye movement abnormalities, such as APN, has been clarified based on correlation of experimental model with lesion localization by neuroimaging in MS. Eye movement disorders have the potential of being utilized as structural and functional biomarkers of early cognitive deficit, and possibly help in assessing disease status and progression, and to serve as platform and functional outcome to test novel therapeutic agents for MS. Knowledge of neuropharmacology applied to eye movement dysfunction has guided testing and use of a number of pharmacological agents to treat some eye movement disorders found in MS, such as APN and other forms of central nystagmus.
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PMID:Eye Movement Abnormalities in Multiple Sclerosis: Pathogenesis, Modeling, and Treatment. 2946 11

MICU1 encodes a Ca2+ sensing, regulatory subunit of the mitochondrial uniporter, a selective calcium channel within the organelle's inner membrane. Ca2+ entry into mitochondria helps to buffer cytosolic Ca2+ transients and also activates ATP production within the organelle. Mutations in MICU1 have previously been reported in 17 children from nine families with muscle weakness, fatigue, normal lactate, and persistently elevated creatine kinase, as well as variable features that include progressive extrapyramidal signs, learning disabilities, nystagmus, and cataracts. In this study, we report the clinical features of an additional 13 patients from consanguineous Middle Eastern families with recessive mutations in MICU1. Of these patients, 12/13 are homozygous for a novel founder mutation c.553C>T (p.Q185*) that is predicted to lead to a complete loss of function of MICU1, while one patient is compound heterozygous for this mutation and an intragenic duplication of exons 9 and 10. The founder mutation occurs with a minor allele frequency of 1:60,000 in the ExAC database, but in ~1:500 individual in the Middle East. All 13 of these patients presented with developmental delay, learning disability, muscle weakness and easy fatigability, and failure to thrive, as well as additional variable features we tabulate. Consistent with previous cases, all of these patients had persistently elevated serum creatine kinase with normal lactate levels, but they also exhibited elevated transaminase enzymes. Our work helps to better define the clinical sequelae of MICU1 deficiency. Furthermore, our work suggests that targeted analysis of the MICU1 founder mutation in Middle Eastern patients may be warranted.
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PMID:A Middle Eastern Founder Mutation Expands the Genotypic and Phenotypic Spectrum of Mitochondrial MICU1 Deficiency: A Report of 13 Patients. 2972 12

Background and aim Chronic musculoskeletal pain, e.g. whiplash associated disorders (WAD), fibromyalgia and myalgia, causes significant burden on both the individual and on society as a whole. In a previous study, the authors concluded that there is a likely connection between chronic benign paroxysmal positional vertigo (BPPV)/canalithiasis and headache, neck pain, generalized pain, fatigue, cognitive dysfunctions as well as tinnitus. The balance dysfunction in BPPV/canalithiasis is dynamic and not static. This leads to a perpetual postural mismatch. The vicious cycle of a disturbed equilibrium control system may be the driving force behind the vicious cycle of pain. The aim of this study is to investigate if otolith-repositioning manoeuvres in patients with chronic BPPV/canalithiasis can be beneficial. Methods During a period of about two years a prospective observational study on patients with chronic musculoskeletal pain referred for physiotherapy was performed. Those with a Dizziness Handicap Inventory (DHI) inquiry score above 20 underwent further investigations to diagnose chronic BPPV/canalithiasis. Diagnostic criteria: (A) The diagnosis of BPPV/canalithiasis was confirmed with the following: (1) specific history of vertigo or dizziness provoked by acceleration/deceleration, AND (2) nystagmus and symptoms during at least one of the test positions; (B) the disorder had persisted for at least one year. Specific otolith repositioning manoeuvre for each semi-circular canal (SCC) was performed. Symptom questionnaire ("yes" or "no" answers during a personal interview) and a follow-up questionnaire were used. Results The responders of the follow-up questionnaire constituted the study group. Thirty-nine patients responded (i.e. 87%) (31 females, 8 males) with a median age of 44 years (17-65). The median duration of the disease was5 years. Seventy-nine percent had ahistory ofhead or neck trauma. The DHI median score was 48 points (score >60 indicates a risk of fall). The video-oculography confirmed BPPV/canalithiasis in more than one semi-circular canal in all patients. In the present study the frequency of affected anterior semi-circular canal (SSC) was at a minimum of 26% and could be as high as 65%. Ninety-five percent suffered from headache, 92% from neck pain, 54% had generalized pain, and 56% had temporo-mandibular joint region pain. Fatigue (97%), aggravation by physical exertion (87%), decreased ability to concentrate (85%) aswellas visual disturbances (85%) were the most frequently reported symptoms, and 49% suffered from tinnitus. The median number of otolith repositioning manoeuvres done was six (2-29). Median time span between finishing otolith repositioning manoeuvres and answering the questionnaire was 7 months. Effects of treatment and conclusion The present study has shown that repositioning of otoliths in the SCCs in nearly all patients with chronic BPPV/canalithiasis ameliorated pain and other symptoms. The correlation between vertigo/dizziness and the majority of symptoms was significant. Therefore, there is strong evidence to suggest that there is a connection between chronic BPPV/canalithiasis and chronic pain as well as the above-mentioned symptoms. Implications Patients with unexplained pain conditions should be evaluated withthe Dizziness Handicap Inventory-questionnaire, which can identify treatable balance disorders.
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PMID:Treatment of chronic canalithiasis can be beneficial for patients with vertigo/dizziness and chronic musculoskeletal pain, including whiplash related pain. 2991 14

Background and aim A diagnosis of chronic benign paroxysmal positional vertigo (BPPV) is based on brief attacks of rotatory vertigo and concomitant nystagmus elicited by rapid changes in head position relative to gravity. However, the clinical course of BPPV may vary considerably from a self-limiting to a persisting and/or recurrent disabling problem. The authors' experience is that the most common complaints of patients with chronic BPPV are nautical vertigo or dizziness with other symptoms including neck pain, headache, widespread musculoskeletal pain, fatigue, and visual disturbances. Trauma is believed to be the major cause of BPPV in individuals younger than fifty years. Chronic BPPV is associated with high morbidity. Since these patients often suffer from pain and do not have rotatory vertigo, their symptoms are often attributed to other conditions. The aim of this study was to investigate possible associations between these symptoms and chronic BPPV. Methods During 2010 a consecutive prospective cohort observational study was performed. Diagnostic criteria: (A) BPPV diagnosis confirmed by the following: (1) a specific history of vertigo/dizziness evoked by acceleration/deceleration, (2) nystagmus in the first position of otolith repositioning maneuvers, and (3) appearing and disappearing nystagmus during the repositioning maneuvers; (B) the disorder has persisted for at least six months. (C) Normal MRI of the cerebrum.
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PMID:Pain and other symptoms in patients with chronic benign paroxysmal positional vertigo (BPPV). 2991 53

Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis characterized by infiltration of organs by CD68+ and CD1a- lipid-laden histiocytes, including the central nervous system in more than a third of patients. Molecular analysis of ECD samples has demonstrated the prevalence of BRAF V600E mutations as high as 54%. Recently, vemurafenib became the only Food and Drug Administration-approved treatment for patients with ECD who carry the BRAF V600E mutation. However, dabrafenib has been suggested to have greater brain distribution. We describe a 44-year-old female patient treated from August of 2015 through November 2017. She presented with a 2-year history of light-headedness, fatigue, and vertigo. She was moderately dysmetric, diffusely hyperreflexic, and dysarthric in the bilateral upper and lower extremities. Her gait was wide-based. She had dysarthria and nystagmus on horizontal gaze bilaterally. Magnetic resonance imaging showed an extensive area of increased T2/fluid-attenuated inversion recovery signal in the brain stem, enhancement in the pons and midbrain, and thickening of the pituitary stalk. Positron emission tomography/computed tomography (PET/CT) and whole-body technetium Tc99m bone scintigraphy showed intense symmetrical radiotracer uptake in the distal femur and tibia bilaterally, which was biopsied. Immunohistochemistry was negative for BRAF V600E, but genomic sequencing revealed the mutation. The patient received combination therapy with dabrafenib and trametinib. Her nystagmus, dysarthria, dysmetria, and gait improved remarkably. Subsequent PET/CT and magnetic resonance imaging showed complete resolution of all radiographic evidence of disease. In this case report, we demonstrate the success of a combination therapy with dabrafenib and trametinib.
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PMID:Dabrafenib and Trametinib Treatment for Erdheim-Chester Disease With Brain Stem Involvement. 3022 65

Primary mitochondrial disorders are a group of clinically variable and heterogeneous inborn errors of metabolism (IEMs), resulting from defects in cellular energy, and can affect every organ system of the body. Clinical presentations vary and may include symptoms of fatigue, skeletal muscle weakness, exercise intolerance, short stature, failure to thrive, blindness, ptosis and ophthalmoplegia, nystagmus, hearing loss, hypoglycemia, diabetes mellitus, learning difficulties, intellectual disability, seizures, stroke-like episodes, spasticity, dystonia, hypotonia, pain, neuropsychiatric symptoms, gastrointestinal reflux, dysmotility, gastrointestinal pseudo-obstruction, cardiomyopathy, cardiac conduction defects, and other endocrine, renal, cardiac, and liver problems. Most phenotypic manifestations are multi-systemic, with presentations varying at different age of onset and may show great variability within members of the same family; making these truly complex IEMs. Most primary mitochondrial diseases are autosomal recessive (AR); but maternally-inherited [from mitochondrial (mt) DNA], autosomal dominant and X-linked inheritance are also known. Mitochondria are unique energy-generating cellular organelles, geared for survival and contain their own unique genetic coding material, a circular piece of mtDNA about 16,000 base pairs in size. Additional nuclear (n)DNA encoded genes maintain mitochondrial biogenesis by supervising mtDNA replication, repair and synthesis, which is modified during increased energy demands or physiological stress. Despite our growing knowledge of the hundreds of genetic etiologies for this group of disorders, diagnosis can also remain elusive due to unique aspects of mitochondrial genetics. Though cure and FDA-approved therapies currently elude these IEMs, and current suggested therapies which include nutritional supplements and vitamins are of questionable efficacy; multi-center, international clinical trials are in progress for primary mitochondrial disorders.
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PMID:Mitochondrial disorders. 3074 Apr 6

Objective: The Epley maneuver (EM) has an immediate effect: rapid reduction of positional nystagmus. Benign paroxysmal positional vertigo (BPPV) causes BPPV fatigue, which constitutes fatigability of positional nystagmus and vertigo with repeated performance of the Dix-Hallpike test; notably, BPPV fatigability becomes ineffective over time. We hypothesized that the immediate effect of the EM is caused by BPPV fatigue. Therefore, we suspected that performance of the EM with intervals between head positions would worsen the immediate reduction of positional nystagmus in patients with BPPV, because BPPV fatigability would become ineffective during performance of this therapy. Methods: Forty patients with newly diagnosed BPPV were randomly assigned to the following two groups; one group performed the EM without intervals between positions (group A), and the other group performed the EM with 3 min intervals between positions (group B). The primary outcome measure was the ratio of maximum slow-phase eye velocity (MSPEV) of positional nystagmus soon after the EM, compared with that measured before the EM. Secondary outcome included whether a 30 min interval after the EM enabled recovery of MSPEV of positional nystagmus to the original value. This study followed the CONSORT 2010 reporting standards. Results: In both groups A and B, the immediate effect of the EM could be observed, because MSPEV during the second Dix-Hallpike test was significantly smaller than MSPEV during the first Dix-Hallpike test (p < 0.0001 in group A, p < 0.0001 in group B). The primary outcome measure was larger in group B than in group A (p = 0.0029). The immediate effect faded 30 min later (secondary outcome). Conclusions: This study showed that the EM had an immediate effect both with and without interval time in each head position of the EM. Because setting interval time in each head position of the EM reduced the immediate effect of the EM, interval time during the EM adds less benefit. This finding can reduce the effort exerted by doctors, as well as the discomfort experienced by patients with pc-BPPV, during EM. However, this immediate effect may be caused by BPPV fatigue, and may fade rapidly. Classification of Evidence: 1b.
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PMID:Effects of Interval Time of the Epley Maneuver on Immediate Reduction of Positional Nystagmus: A Randomized, Controlled, Non-blinded Clinical Trial. 3101 86

Introduction: Patients with chronic vestibular multi-canalicular canalithiasis (CVMCC) can have serious morbidities, for example, musculoskeletal pain, dizziness, fatigue, and cognitive difficulties. Involvement of the anterior semi-circular canal (SCC) is common in CVMCC. A mono-canalicular diseased anterior SCC is rare.Aim: To examine if the Bending forward test can be used to detect a diseased anterior semi-circular canal in patients with CVMCC.Material and Methods: Prospective consecutive observational cohort study in patients with relapse of an earlier successfully treated chronic CVMCC, where 16 patients have a diseased anterior SCC, 11 without any involvement of the anterior SCC, and 15 healthy controls. Patients are tested in sitting and in bending forward position. The difference in downwards directed nystagmus count and slow phase velocity in the two test positions AND reported movement illusion are the main outcome.Results: The sensitivity of the Bending forward-test is 81%; the specificity 91%. Five of the healthy controls have positional nystagmus without movement illusion. This is interpreted as cupulolithiasis. Positional nystagmus with movement illusion is interpreted as canalithiasis.Conclusions: Bending forward-test is a valuable test. Only positional nystagmus accompanied by a movement illusion, that is canalithiasis, is of clinical relevance.Significance: These findings may assist in diagnosing compound musculoskeletal disorders.
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PMID:Can the bending forward test be used to detect a diseased anterior semi-circular canal in patients with chronic vestibular multi-canalicular canalithiasis (BPPV)? 3158 60


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