ABSTRACT
BACKGROUND: The recreational use of nitrous oxide (N2O) has increased in recent years with a noticeable surge in the incidence of nitrous oxide-related myeloneuropathy. OBJECTIVES: To raise awareness of increasing myeloneuropathy due to recreational nitrous oxide misuse in Israel. METHODS: We conducted a case series documenting the clinical and investigative features of eight patients presenting with nitrous oxide-induced myeloneuropathy who were admitted to our departments. RESULTS: Paresthesia was the chief complaint in all patients, with sensory gait ataxia being a common feature, which was often accompanied by Romberg's sign and mild lower limb weakness. Vitamin B12 levels were below the normal range in seven patients, accompanied by elevated homocysteine and methylmalonic acid levels. Magnetic resonance imaging scans revealed hyperintense signals in the dorsal columns of the cervical spine. All patients improved following vitamin B12 injections. CONCLUSIONS: Enhancing awareness, prompting the use of appropriate investigations, and advocating for timely treatment are needed to overcome the risks associated with nitrous oxide misuse.
Subject(s)
Magnetic Resonance Imaging , Nitrous Oxide , Vitamin B 12 , Humans , Nitrous Oxide/adverse effects , Nitrous Oxide/administration & dosage , Male , Adult , Vitamin B 12/administration & dosage , Female , Israel/epidemiology , Magnetic Resonance Imaging/methods , Spinal Cord Diseases/chemically induced , Paresthesia/chemically induced , Paresthesia/diagnosis , Middle Aged , Recreational Drug Use , Gait Ataxia/chemically induced , Gait Ataxia/etiology , Young Adult , Substance-Related Disorders/complications , Vitamin B 12 Deficiency/chemically induced , Vitamin B 12 Deficiency/diagnosisABSTRACT
There are scarce reports of riboflavin-responsive lipid storage myopathy in elderly patients with onset in their sixties. We describe three elderly patients with riboflavin-responsive lipid-storage myopathy. All three patients (aged 67-71 years on first examination) had subacute onset of neck extensors and proximal limb weakness progressing to inability to rise from a sitting position or to walk. Muscle biopsies showed vacuoles with lipid content, mainly in type 1 fibers. Genetic analysis failed to identify any pathogenic variant in one patient, identified a heterozygous variant of uncertain significance c.812 A > G; p.Tyr271Cys in the ETFDH gene in the second patient, and revealed a heterozygote likely pathogenic variant c.1286-2 A > C in the ETFDH gene predicted to cause abnormal splicing in the third patient. All patients responded to treatment with riboflavin and carnitine, and regained normal strength. This report emphasizes the importance of muscle biopsy in revealing treatable lipid storage myopathy in elderly patients with progressive myopathy of unidentifiable cause.
Subject(s)
Iron-Sulfur Proteins , Lipid Metabolism, Inborn Errors , Multiple Acyl Coenzyme A Dehydrogenase Deficiency , Muscular Diseases , Muscular Dystrophies , Oxidoreductases Acting on CH-NH Group Donors , Humans , Aged , Muscle, Skeletal/metabolism , Multiple Acyl Coenzyme A Dehydrogenase Deficiency/drug therapy , Multiple Acyl Coenzyme A Dehydrogenase Deficiency/genetics , Electron-Transferring Flavoproteins/genetics , Iron-Sulfur Proteins/genetics , Oxidoreductases Acting on CH-NH Group Donors/genetics , Muscular Diseases/drug therapy , Muscular Diseases/genetics , Muscular Diseases/pathology , Riboflavin/therapeutic use , LipidsABSTRACT
X-linked myopathy with excessive autophagy (XMEA) is a rare disorder characterized by slow progressive muscle weakness and distinctive pathology of excessive autophagic vacuoles on muscle biopsy. Here we report on five patients, in a single family, with proximal lower limb weakness. The proband, a 25-year-old man, presented with 5 years of progressive lower limbs proximal muscle weakness. His maternal grandfather and three of his maternal male cousins had similar clinical findings and were initially suspected to have Becker muscular dystrophy. Muscle biopsy in two affected family members demonstrated autophagic myopathy, and guided the genetic investigations to the identification of a pathogenic mutation, c.272G > C in the VMA21 gene, known to cause XMEA [1]. To the best of our knowledge this is the first identified Israeli Jewish family afflicted by XMEA.
Subject(s)
Genetic Diseases, X-Linked/diagnosis , Muscle Weakness/pathology , Muscular Diseases/diagnosis , Vacuolar Proton-Translocating ATPases , Adult , Autophagy/genetics , Biopsy , Humans , Israel , Lower Extremity/pathology , Male , Muscle, Skeletal/pathology , Mutation , Vacuolar Proton-Translocating ATPases/genetics , Young AdultABSTRACT
To determine whether there are differences in measures of cognitive function between second and third trimester pregnant women compared to non-pregnant controls. This prospective study comprised 40 pregnant and 40 non-pregnant women, 20-40 years old, native-Hebrew speakers who were recruited from the outpatient clinics during a period of nearly 2 years. The patients underwent cognitive and affective evaluation. The performance on the three following tests: difficult and total items of Verbal Paired Associates, the Digit Span-forward and the Naming Objects and Fingers test scores were significantly better among non- pregnant women. All the other test results were similar between the two groups, including the depression scores. On multivariate linear regression analysis, after adjusting for age and years of education , Verbal Paired Associates total score (p = 0.04), and Naming Objects and Fingers (p = 0.01) remained significantly associated with pregnancy, but not Digit Span (p = 0.09). Our study demonstrates an impairment in memory among pregnant women. Furthermore language skills, particularly naming, were also impaired, a finding which has not been previously described.
Subject(s)
Cognition Disorders/epidemiology , Language , Neuropsychological Tests/statistics & numerical data , Adult , Case-Control Studies , Cognition Disorders/diagnosis , Cognition Disorders/psychology , Female , Humans , Israel/epidemiology , Pregnancy , Prospective Studies , Young AdultABSTRACT
ABSTRACT: Glycogen storage disease type III is a rare inherited disease caused by decreased activity of glycogen debranching enzyme. It affects primarily the liver, cardiac muscle, and skeletal muscle. Pure involvement of the skeletal muscle with adult onset is extremely rare. We report on a patient with myopathy due to glycogen storage disease III, and describe the clinical features, and pathologic and genetic findings.
Subject(s)
Glycogen Storage Disease Type III/diagnosis , Muscular Diseases/etiology , Humans , Male , Middle Aged , Muscle, SkeletalABSTRACT
INTRODUCTION: Small-fiber neuropathy is rare in children. It has been associated with several autoimmune disorders, but there are no reports of an autoinflammatory etiology. METHODS: The data of four children/adolescents presenting with erythromelalgia and neuropathic pain from 2014 to 2019 were collected retrospectively from the electronic database of a pediatric medical center. RESULTS: Results of clinical and/or electrophysiological evaluation excluded large nerve fiber involvement. Skin biopsy results confirmed small-fiber neuropathy. According to genetic analysis, two patients were heterozygous and one was homozygous for mutations in the familial Mediterranean fever (MEFV) gene. Behcet disease was diagnosed in the fourth patient. Treatment with anti-interleukin-1 agents, intravenous immunoglobulin, and glucocorticoids was beneficial. DISCUSSION: The diagnosis of small-fiber neuropathy should be considered in children/adolescents presenting with erythromelalgia. A thorough investigation is required to reveal the underlying disorder. Clinicians should be alert to the peripheral neurological manifestations of autoinflammatory syndromes because effective treatments are available.
Subject(s)
Erythromelalgia/complications , Erythromelalgia/diagnosis , Small Fiber Neuropathy/complications , Small Fiber Neuropathy/diagnosis , Adolescent , Autoimmune Diseases/complications , Autoimmune Diseases/diagnosis , Autoimmune Diseases/physiopathology , Child , Erythromelalgia/physiopathology , Female , Humans , Inflammation/complications , Inflammation/diagnosis , Inflammation/physiopathology , Retrospective Studies , Small Fiber Neuropathy/physiopathology , SyndromeABSTRACT
Introduction: Myelin oligodendrocyte glycoprotein (MOG) antibody associated disorders (MOGAD) have been recognized over the past 10 years as distinct inflammatory, demyelinating diseases of the central nervous system (CNS). Antibodies against MOG are found mostly in patients with optic neuritis (ON), acute disseminated encephalomyelitis (ADEM), and aquaporin-4 antibody (AQP4-abs)-seronegative neuromyelitis optica spectrum disorders (NMOSD). However, data on the disease course and disability outcomes of these patients are scarce. Aim: To describe clinical and paraclinical features associated with MOG antibodies (abs) in a cohort of patients in Israel, and to assess baseline prognostic features of MOG-ab-associated diseases after a first acute demyelinating event. Methods: MOG-abs were identified in serum using a cell-based assay, and clinical data were collected from the patients' medical records. Results: Of 683 patients with demyelinating diseases tested for MOG-abs, 53 were positive (7.7%), with ON the most common presenting phenotype (68%). The age range of MOG-abs seropositive patients was 1-66 years, with increased prevalence in children (19% compared to 6.7% in adults) (p < 0.01). The highest prevalence of seropositivity was observed in children aged younger than 10 years (25.5%), followed by those aged 31-40 years (16.6%). Conclusions: MOGAD are distinct autoimmune diseases that occurs at all stages of life with a significantly higher prevalence in children; the main clinical presenting phenotype in the entire cohort is ON and young children most often presented with ON or ADEM. Our data highlight the need for repeated evaluation of MOG-abs in patients with acquired CNS demyelinating disorders, especially in children under 10 and adults between 31 and 40 years of age.
ABSTRACT
Hand weakness and wasting in the setting of mid-cervical spondylosis and disc herniation without radiological evidence for compression of the C8 or T1 roots has been rarely reported. We retrospectively studied the data of patients with hand weakness and mid-cervical spondylosis. The clinical and radiological findings were compared to a control group of patients with weakness of the arm or forearm muscles and similar mid-cervical spondylosis. We found 19 patients with weakness and atrophy of the intrinsic hand muscles, and 13 patients with weakness proximal to the hand muscles to serve as a control group. Eleven patients (58%) had lower limb hyperreflexia or Babinski sign. Nine patients (47%) had compression of the C7 root, 12 patients (63%) had compression of C6, 8 patients (42%) had compression of C5, and 2 patients (11%) had compression of the root C4. In all but three patients (84%), magnetic resonance imaging (MRI) showed cord compression. In the control group, five patients (38%) showed hyperreflexia of the lower limbs and Babinski sign. Five patients (38%) had compression of the C7 root, eight patients (62%) had compression of C6, and twelve patients (92%) had compression of C5. Cord compression was found in eight patients (62%). Hand muscle weakness and wasting due to mid-cervical spondylosis seems to be more common than usually believed. The lack of clinical-radiological correlation should not mislead the clinician from the correct diagnosis, and should not delay the surgical decompression of the cord and the roots.
Subject(s)
Hand/physiopathology , Intervertebral Disc Displacement/complications , Muscle Weakness/etiology , Nerve Compression Syndromes/complications , Radiculopathy/etiology , Spinal Cord Compression/complications , Spondylosis/complications , Adult , Aged , Cervical Vertebrae , Female , Humans , Male , Middle Aged , Retrospective Studies , Thoracic VertebraeABSTRACT
Peripheral neuropathic pain (PNP) is caused by neuronal damage to the peripheral nervous system and usually affects the distal extremities. This open-label study examined the effect of short-term peripheral nerve stimulation (PNS) on individuals with PNP due to polyneuropathy. A total of 12 patients (mean age, 63.0 ± 10.0 years, 41.7% male) with daily bilateral PNP for at least 6 months (mean duration, 7.4 ± 7.8 years) received a total of six direct electrical stimulation therapies to the posterior tibial nerve at 3-4-day intervals. Eight patients completed the study and were included in the efficacy analysis. The average pain at baseline was 36.6 ± 3.80 estimated by the Short-Form McGill Pain Questionnaire. After the last stimulation, pain was significantly reduced by 85.5% to 4.88 ± 3.1 (p = 0.008). Six patients (75%) had over 50% decrease in pain after the first stimulation therapy and 99.2% after the final stimulation therapy. The patients also reported statistically significant decreases in pain level (measured by visual analog scale), ranging from 54.85% to 87.50% after each of the stimulations as compared to the pain experienced prior to the stimulations. The procedure was safe without any serious adverse events. PNS has demonstrated excellent efficacy and improvement of PNP symptoms. Further studies in larger patient populations are warranted.
ABSTRACT
OBJECTIVE: To investigate the correlation between cardiovascular risk factors (CVRFs) and vestibular neuritis (VN) in hospitalized adult patients. METHODS: A cross-sectional retrospective study was conducted in a tertiary hospital setting. The medical records of patients (aged over 18 years old) who were hospitalized between the years 2005 and 2014 with the diagnosis of VN were retrieved. Inclusion criteria were: (1) acute vertigo lasting for at least 24 hours, (2) absence of auditory complaints, (3) horizontal unidirectional nystagmus present during physical examination, and (4) absence of neurological symptoms or signs. The ratio of CVRFs among VN patients was compared to the ratio of those among the general Israeli population. RESULTS: A significantly higher prevalence of CVRFs was found among VN hospitalized patients in comparison to the general population ( P < .05). Furthermore, a significant correlation ( P < .001) was found between the patients' age and the number of CVRFs (r = .387). A positive correlation (r = .643) was found between the number of CVRFs and VN in each age group ( P = .119). CONCLUSION: There may be a possible interrelation between CVRFs and VN. This correlation can be caused by occlusion of small blood vessels leading to labyrinthine ischemia and apparition of symptoms of VN.
Subject(s)
Diabetes Mellitus/epidemiology , Hyperlipidemias/epidemiology , Hypertension/epidemiology , Obesity/epidemiology , Sedentary Behavior , Smoking/epidemiology , Vestibular Neuronitis/epidemiology , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Cardiovascular Diseases/epidemiology , Coronary Disease/genetics , Cross-Sectional Studies , Female , Hospitalization , Humans , Male , Medical History Taking , Middle Aged , Nystagmus, Pathologic/epidemiology , Nystagmus, Pathologic/etiology , Retrospective Studies , Risk Factors , Sex Factors , Tertiary Care Centers , Vertigo/epidemiology , Vertigo/etiology , Vestibular Neuronitis/complications , Young AdultABSTRACT
BACKGROUND: Human skeletal muscles express three major myosin heavy chain (MyHC) isoforms: MyHCIIx (MYH1) in fast type 2B muscle fibers, MyHCIIa (MYH2) in fast type 2A fibers and MyHCI/ß-cardiac MyHC (MYH7) in slow type I skeletal fibers and cardiac ventricles. In line with its expression pattern, MYH7 mutations have been reported in association with hypertrophic or dilated cardiomyopathy, skeletal myopathies or a combination of both. We analyzed the clinical and molecular phenotype of two unrelated families of Jewish Moroccan ancestry that presented with apparently autosomal dominant inheritance of progressive Laing-like distal myopathy with non-specific myopathic changes, but uncommon marked contractures and wasting of the neck extensors. METHODS: Clinical phenotyping, whole exome sequencing and restriction analysis, generation of mutants followed by cell culture transfection and imaging. RESULTS: Using whole exome sequencing we identified in both families two novel heterozygous proline substitutions located in exon 31 of MYH7 within its rod domain: c.4309G>C (p.Ala1437Pro) and c.4301G>C (p.Arg1434Pro). Here we show that the phenotype caused by these mutations includes marked cervical muscle contracture, and report that the severity of the phenotype varies significantly, to the extent of non-penetrance in one of the families. Finally, we provide evidence that both proline substitutions impair myosin self-assembly in non-muscle cells transfected with ß-myosin constructs carrying the mutations, but do not prevent incorporation of the mutant molecules into the sarcomere. CONCLUSIONS: This study expands our clinical and molecular knowledge of MYH7 rod mutations causing skeletal myopathies, and underscores the importance of discussing disease penetrance during genetic counseling.
Subject(s)
Cardiac Myosins/genetics , Contracture/genetics , Distal Myopathies/genetics , Myosin Heavy Chains/genetics , Proline/metabolism , Adult , Aged , Amino Acid Substitution/genetics , Animals , Back/diagnostic imaging , Back/pathology , COS Cells , Chlorocebus aethiops , DNA/chemistry , DNA/isolation & purification , DNA/metabolism , Distal Myopathies/pathology , Female , Heterozygote , Humans , Male , Muscle, Skeletal/metabolism , Muscle, Skeletal/pathology , Neck/diagnostic imaging , Neck/pathology , Phenotype , Polymorphism, Single Nucleotide , Proline/geneticsABSTRACT
Gain-of-function mutations in the SCN10A gene (encoding the Nav1.8 voltage gated sodium channel) have been reported in a small number of patients. All presented with predominantly painful sensory neuropathy, congruent with the expression of Nav1.8 in nociceptive sensory neurons of the dorsal root ganglion. Only a few had mild autonomic symptoms, including dry eyes and mouth, orthostatic dizziness, palpitations, diarrhea and constipation. The underlying mechanism of the autonomic symptoms in these patients is unclear. We describe a 37-year-old woman with severe progressive gastroparesis and diffuse painful small fiber sensory neuropathy that started at age 32. Due to the severe dysphagia she could not ingest solid food, and lost eight kilograms. The gastroparesis was documented by esophageal manometry and gastric scintigraphy. The neuropathic pain started distally and then intensified and spread to most body areas. The patient harbored a novel heterozygous mutation: c.G4915A:p.D1639N in the SCN10A gene. To the best of our knowledge, this is the first description of such a phenotype due to a Nav1.8 mutation. Thus, our study expands the clinical spectrum of Nav1.8 associated disorders, and suggests that mutations in this sodium channel should be considered in patients with gastrointestinal motility dysfunction and painful neuropathy.
Subject(s)
Erythromelalgia/genetics , Gastroparesis/genetics , Mutation , NAV1.8 Voltage-Gated Sodium Channel/genetics , Pain/genetics , Peripheral Nervous System Diseases/genetics , Adult , Erythromelalgia/complications , Female , Ganglia, Spinal , Gastroparesis/complications , Humans , Nociceptors , Pain/complications , Peripheral Nervous System Diseases/complications , PhenotypeABSTRACT
Rarely, inflammation can be present in genetic myopathies, such as dysferlinopathies, facioscapulohumeral muscular dystrophy and GNE-myopathy (hereditary inclusion body myopathy). This may lead to erroneous initial diagnosis and unnecessary therapy which bear serious side effects. We report on an unusual case of mutations in the TTN gene presenting with inflammatory infiltrates in the muscle biopsy. Only after intensive immune-modulating therapies failed, a genetic myopathy was considered. Exome sequencing and search for mutated muscle protein-encoding genes disclosed compound heterozygous mutations in TTN: K26320T and A6135G. The parents carry one each of the mutations. Titinopathy could be considered also in patients presenting with inflammatory infiltrates resistant to therapy.
Subject(s)
Connectin/genetics , Muscular Dystrophies, Limb-Girdle/diagnosis , Muscular Dystrophies, Limb-Girdle/genetics , Adult , Age of Onset , Humans , Male , Myositis/diagnosisABSTRACT
GNE Myopathy (GNEM) is a neuromuscular disorder caused by mutations in the GNE gene. It is a slowly progressive distal and proximal muscle weakness sparing the quadriceps. In this study, we applied our model of mutated M743T GNE enzyme skeletal muscle-cultured myoblasts and paired healthy controls to depict the pattern of signaling proteins controlling survival and/or apoptosis of the PI3K/AKT, BCL2, ARTS/XIAP pathways, examined the effects of metabolic changes/stimuli on their expression and activation, and their potential role in GNEM. Immunoblot analysis of the GNEM myoblasts indicated a notable increased level of activated PTEN and PDK1 and a trend of relative differences in the expression and activation of the examined signaling molecules with variability among the cultures. ANOVA analysis showed a highly significant interaction between the level of PTEN and the patients groups. In parallel, the interaction between the level of BCL2, BAX and PTEN with the specific PI3K/AKT inhibitor-LY294002 was highly significant for BCL2 and nearly significant for PTEN and BAX. The pattern of the ARTS/XIAP signaling proteins of GNEM and the paired controls was variable, with no significant differences between the two cell types. The response of the GNEM cells to the metabolic changes/stimuli: serum depletion and insulin challenge, as indicated by expression of selected signaling proteins, was variable and similar to the control cells. Taken together, our observations provide a clearer insight into specific signaling molecules influencing growth and survival of GNEM muscle cells.
Subject(s)
Distal Myopathies/metabolism , Distal Myopathies/pathology , Multienzyme Complexes/genetics , Multienzyme Complexes/metabolism , Mutant Proteins/genetics , Mutant Proteins/metabolism , Myoblasts, Skeletal/metabolism , Myoblasts, Skeletal/pathology , Signal Transduction/physiology , Adult , Apoptosis , Case-Control Studies , Cell Survival , Cells, Cultured , Distal Myopathies/genetics , Female , Humans , Male , Middle Aged , Mutation , PTEN Phosphohydrolase/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Protein Serine-Threonine Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Pyruvate Dehydrogenase Acetyl-Transferring Kinase , Septins/metabolism , X-Linked Inhibitor of Apoptosis Protein/metabolism , Young AdultABSTRACT
AIM: The association between migraine and cerebrovascular disease is well documented in younger migraine patients, especially those with aura. Prevalence estimates of vascular risk factors among elderly migraine sufferers are lacking. The present study was designed to estimate the prevalence of vascular risk factors in the elderly population with late onset of migraine without aura. METHODS: The medical records of 163 patients aged 50 years and older suffering from migraine without aura were assessed for vascular risk factors, including hypertension, elevated serum lipid levels, diabetes mellitus and cardiovascular disease. Prevalence was estimated and compared with age- and sex-matched vascular risk factor estimates for the general population extracted from the 2003-2004 Israeli National Health Interview Survey, and to a group of patients matched by age suffering from migraine with aura. RESULTS: Among women with migraine without aura, hypertension, hyperlipidemia and diabetes mellitus were significantly less prevalent than among women without migraine without aura. Prevalence estimates for vascular risk factors did not differ by migraine among males. The group of older patients suffering from migraine with aura showed a higher incidence of vascular risk factors in respect to the group of migraine patients without aura. CONCLUSIONS: The findings of the present study might have an important clinical relevance, suggesting another pathophysiological process in respect to patients suffering from migraine with aura, and this evidence might have different therapeutic implications.
Subject(s)
Cerebrovascular Disorders/complications , Migraine Disorders/etiology , Risk Assessment/methods , Aged , Aged, 80 and over , Cerebrovascular Disorders/epidemiology , Female , Humans , Incidence , Israel/epidemiology , Male , Middle Aged , Migraine Disorders/epidemiology , Prevalence , Retrospective Studies , Risk Factors , Surveys and QuestionnairesABSTRACT
Centronuclear myopathy (CNM) is a rare hereditary myopathy characterized by centrally located muscle fiber nuclei. Mutations in the dynamin 2 (DNM2) gene are estimated to account for about 50 % of CNM cases. Electromyographic recordings in CNM may show myopathic motor unit potentials without spontaneous activity at rest. Myotonic discharges, a distinctive electrical activity caused by membrane hyperexcitability, are characteristic of certain neuromuscular disorders. Such activity has been reported in only one CNM case without a known genetic cause. We sequenced the DNM2 gene and the genes associated with myotonia (CLCN1, SCN4A, DMPK and ZNF9) in a sporadic adult patient with CNM and myotonic discharges. Sequencing the entire coding region and exon-intron boundaries revealed a heterozygous c.1106g-a substitution in exon 8, resulting in a R369Q change in the DNM2. Sequencing the CLCN1, SCN4A, DMPK and ZNF9 genes ruled out mutations in these genes. This is the first report of DNM2-related CNM presenting with myotonia. The diagnosis of CNM should be considered in patients with myotonic discharges of an unknown cause.
Subject(s)
Dynamin II/genetics , Myopathies, Structural, Congenital/complications , Myopathies, Structural, Congenital/genetics , Myotonia/complications , Myotonia/genetics , Adult , Base Sequence , Chloride Channels/genetics , DNA Mutational Analysis , Electromyography , Female , Humans , Muscle, Skeletal/pathology , Muscle, Skeletal/physiopathology , Myopathies, Structural, Congenital/pathology , Myopathies, Structural, Congenital/physiopathology , Myotonia/pathology , Myotonia/physiopathology , Myotonin-Protein Kinase/genetics , NAV1.4 Voltage-Gated Sodium Channel/genetics , RNA-Binding Proteins/geneticsABSTRACT
BACKGROUND: Type 1 diabetes in humans is an autoimmune disease in which Tcells target pancreatic islets of Langerhans, leading to the progressive destruction of the insulin-producing beta cells. Both genetic and environmental factors contribute to the development of autoimmune diabetes. The non-obese diabetic (NOD) mouse model of human type 1 diabetes demonstrates two missense mutations in the transient receptor potentialvanilloid receptor-1 (TRPVi) gene. OBJECTIVES: To investigate whether polymorphism in the TRPV1 gene may play a role in the predisposition to human type 1 diabetes. METHODS: We genotyped 146 Ashkenazi Jewish type 1 diabetic patients and 205 Ashkenazi Jewish healthy controls for the rs222747 (M3151), rs224534 (T4691) and rs8065080 (1585V) variants of the TRPV1 gene. RESULTS: There was a significant increase in the rs222747 (M3151) variant of the TRPV1 gene in the type 1 diabetes cohort compared to the control: rs222747 (M3151) homozygous: (61% vs. 48.3%, P = 0.02). Logistic regression analysis revealed that type 1 diabetes was significantly associated with rs222747 (M3151), such that having diabetes increased the odds of rs222747 homozygosity (M3151) by 67.2%, odds ratio 1.6, 95% confidence interval 1.08-2.57, P < 0.02. No difference was found in the rs224534 (T4691) and rs8065080 (1585V) allelic variants. There was no difference in any of the TRPV1 variants by gender, age when type 1 diabetes was diagnosed, body mass index, glycemic control, blood pressure, positive autoantibodies (ICA, GAD, IAA), and other autoimmune diseases. CONCLUSIONS: Our study demonstrates that TRPV1 may be a susceptible gene for type 1 diabetes in an Ashkenazi Jewish population. These results should be replicated in the same ethnic group and in other ethnic groups.
Subject(s)
Diabetes Mellitus, Type 1/genetics , Jews/genetics , TRPV Cation Channels/genetics , Adult , Female , Genetic Predisposition to Disease , Humans , Logistic Models , Male , Polymorphism, Single NucleotideABSTRACT
BACKGROUND: In rare cases of cervical myelopathy, there may be a discrepancy between the sensory level and the site of cord lesion. This phenomenon is not well recognized. This study sought to investigate the characteristics of patients presenting with a false localizing thoracic sensory level. METHODS: The databases of the neurology clinics of two major tertiary medical centers were reviewed for all patients who presented in 2000-2010 with a main complaint of paraparesis and a thoracic sensory level. Those whose initial thoracic magnetic resonance scan showed no spinal cord pathology were included in the study. RESULTS: Twelve patients (mean age, 52 ± 31 years) met the study criteria. In all cases, the pathological lesion was visualized on magnetic resonance imaging of the cervical spine or brain. Eight patients had a compressive lesion of the spinal cord and 4 had demyelinating lesions. The difference between the false localizing sensory level and the level of the cervical lesion ranged from 6 to 11 segments. CONCLUSION: Patients with a sensory thoracic level and normal findings on thoracic magnetic resonance imaging should be further evaluated with cervical spinal cord and, sometimes, brain imaging to search for potentially treatable lesions.
Subject(s)
Brain/pathology , Cervical Vertebrae/pathology , Spinal Cord Compression/pathology , Spinal Cord/pathology , Adult , Aged , Aged, 80 and over , Humans , Intervertebral Disc Displacement/diagnosis , Intervertebral Disc Displacement/pathology , Magnetic Resonance Imaging/methods , Middle Aged , Paraparesis/diagnosis , Paraparesis/pathology , Spinal Cord Compression/diagnosis , Young AdultABSTRACT
Traumatic brain injury (TBI) is a major cause of seizures in the general population. Several studies have shown an increased risk of epilepsy after traumatic brain injury, depending on risk factors, such as severity and time post trauma. The aim of our study was to evaluate the appearance of late seizures after a very mild head trauma or whiplash injury. All patients admitted to the emergency room after a very mild head trauma or whiplash injury during 2008-2010 were evaluated prospectively within 24 hours of the event and followed up 1 year later for evaluation of seizure appearance. The appearance of seizures in the head trauma or whiplash injury group was compared to a control group of orthopedic injury patients. A total of 2999 patients were included in the study--2005 patients with involvement of head and spine trauma and 994 in an orthopedic control group. Three patients (0.1%) out of the whole study group developed seizures: 2 (0.18%) in the head trauma group and 1 (0.1%) in the control group. The conclusion of the study was that post trauma seizure incidence is not significantly different in patients with very mild head or spine trauma and is similar respective to subjects with no non-head or cervical spine injury. This may have medico-legal repercussions.