Abstract:
OBJECTIVE:Thymidine kinase 2, encoded by the nuclear gene TK2, is required for mitochondrial DNA maintenance. Autosomal recessive TK2 mutations cause depletion and multiple deletions of mtDNA that manifest predominantly as a myopathy usually beginning in childhood and progressing relentlessly. We investigated the safety and efficacy of deoxynucleoside monophosphate and deoxynucleoside therapies. METHODS:We administered deoxynucleoside monophosphates and deoxynucleoside to 16 TK2-deficient patients under a compassionate use program. RESULTS:In 5 patients with early onset and severe disease, survival and motor functions were better than historically untreated patients. In 11 childhood and adult onset patients, clinical measures stabilized or improved. Three of 8 patients who were nonambulatory at baseline gained the ability to walk on therapy; 4 of 5 patients who required enteric nutrition were able to discontinue feeding tube use; and 1 of 9 patients who required mechanical ventilation became able to breathe independently. In motor functional scales, improvements were observed in the 6-minute walk test performance in 7 of 8 subjects, Egen Klassifikation in 2 of 3, and North Star Ambulatory Assessment in all 5 tested. Baseline elevated serum growth differentiation factor 15 levels decreased with treatment in all 7 patients tested. A side effect observed in 8 of the 16 patients was dose-dependent diarrhea, which did not require withdrawal of treatment. Among 12 other TK2 patients treated with deoxynucleoside, 2 adults developed elevated liver enzymes that normalized following discontinuation of therapy. INTERPRETATION:This open-label study indicates favorable side effect profiles and clinical efficacy of deoxynucleoside monophosphate and deoxynucleoside therapies for TK2 deficiency. ANN NEUROL 2019;86:293-303.
journal_name
Ann Neuroljournal_title
Annals of neurologyauthors
Domínguez-González C,Madruga-Garrido M,Mavillard F,Garone C,Aguirre-Rodríguez FJ,Donati MA,Kleinsteuber K,Martí I,Martín-Hernández E,Morealejo-Aycinena JP,Munell F,Nascimento A,Kalko SG,Sardina MD,Álvarez Del Vayo C,Serranodoi
10.1002/ana.25506subject
Has Abstractpub_date
2019-08-01 00:00:00pages
293-303issue
2eissn
0364-5134issn
1531-8249journal_volume
86pub_type
杂志文章,多中心研究abstract::The first electrophysiological study of the human lateral geniculate nucleus (LGN), optic radiation, striate, and extrastriate visual areas is presented in the context of presurgical evaluation of three epileptic patients (Patients 1, 2, and 3). Visual-evoked potentials to pattern reversal and face presentation were r...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.10403
更新日期:2003-01-01 00:00:00
abstract::Early differential diagnosis of motor neuropathies (MN) and lower motor neuron diseases (LMND) is important, as prognosis and therapeutic approaches are different. We evaluated the diagnostic contribution of the biopsy of the motor branch of the obturator nerve and gracilis muscle in 21 consecutive patients in which, ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.22110
更新日期:2011-01-01 00:00:00
abstract:OBJECTIVE:Neuronal channelopathies cause brain disorders, including epilepsy, migraine, and ataxia. Despite the development of mouse models, pathophysiological mechanisms for these disorders remain uncertain. One particularly devastating channelopathy is Dravet syndrome (DS), a severe childhood epilepsy typically cause...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.23897
更新日期:2013-07-01 00:00:00
abstract::Three patients with inferior branch palsies of the oculomotor nerve are described. Two were under 10 years of age and the third was 30 years old at the onset. All 3 presented with painless diplopia. The onset was sudden in 2 patients and progressive in the third. The palsy cleared within a short time in the 2 patients...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410020414
更新日期:1977-10-01 00:00:00
abstract::Noradrenergic fibers were identified in rat cervical lymph nodes by fluorescence histochemistry and confirmed by radioenzymatic determination of norepinephrine. After superior cervical ganglionectomy, lymph node norepinephrine and noradrenergic fluorescence were strikingly decreased. The alpha-adrenergic radioligand [...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410080509
更新日期:1980-11-01 00:00:00
abstract::Two patients with biopsy-proved progressive multifocal leukoencephalopathy (PML) were treated with near-maximal doses of adenine arabinoside (Ara-A), 18.6 and 20 mg per kilogram of body weight per day for 14 days. In both patients, clinical progression of the disease was correlated with an increase in the size of low-...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410010509
更新日期:1977-05-01 00:00:00
abstract:OBJECTIVE:To examine the association between odor identification deficits and future mortality in a multiethnic community cohort of older adults. METHODS:Participants were evaluated with the 40-item University of Pennsylvania Smell Identification Test (UPSIT). Follow-up occurred at 2-year intervals with information on...
journal_title:Annals of neurology
pub_type: 杂志文章,随机对照试验
doi:10.1002/ana.24447
更新日期:2015-09-01 00:00:00
abstract::Calmodulin is a major Ca2+ -binding protein that may mediate many Ca2+ -regulated processes in neuronal function. Calmodulin is present in the presynaptic nerve terminal in association with synaptic vesicles and in postsynaptic density fractions. Several calmodulin-regulated synaptic biochemical processes have been id...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410160716
更新日期:1984-01-01 00:00:00
abstract::Two women suffered from a similar, slowly progressive illness characterized by upper and lower motor neuron involvement, sensory disturbances, and neurogenic bladder. Radiographic examinations showed cerebral atrophy and, in one, changes on computerized tomography suggesting leukodystrophy. Sural nerve biopsies reveal...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410130411
更新日期:1983-04-01 00:00:00
abstract::We examined the expression of Fas antigen and Bcl-2 protein in thymic tissue surgically resected from 10 patients with myasthenia gravis, using immunocytochemical techniques. Histologically, thymic tissues from 7 myasthenia gravis patients showed hyperplasia, while 3 other patients had thymomas. In hyperplastic thymic...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410390414
更新日期:1996-04-01 00:00:00
abstract::Analysis of the pathophysiology of hypokalemic paralysis, as it occurs in barium poisoning, chronic potassium deficiency, and thyrotoxicosis, suggests that these disorders may have a similar mechanism. An increased ratio of muscle sodium permeability to potassium permeability reduces the ionic diffusion potential, whi...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410110602
更新日期:1982-06-01 00:00:00
abstract::Based on prior reports of free light chains of immunoglobulin G (IgG) in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS), we quantitated free kappa and lambda chains and whole IgG concentrations using sensitive and specific radioimmunoassays (RIAs). The RIA for free kappa chains had a sensitivit...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410200111
更新日期:1986-07-01 00:00:00
abstract::Pallidopyramidal disease is a rare disease of young patients in which they manifest a parkinsonian syndrome and pyramidal signs. Pallidopyramidal disease has been attributed to a degeneration of the pallidum and the pyramidal tract, although only 1 patient has been studied postmortem. In the present report, [18F]fluor...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410380618
更新日期:1995-12-01 00:00:00
abstract::Glucose metabolism is depressed in the temporal and parietal regions of the cortex in patients with Alzheimer's disease. We measured the concentrations of two glucose transporters, GLUT1 and GLUT3, in six regions of brains from both control subjects and patients with Alzheimer's disease. The concentrations of both tra...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410350507
更新日期:1994-05-01 00:00:00
abstract::Mutations of copper,zinc-superoxide dismutase (cu,zn SOD) are found in patients with a familial form of amyotrophic lateral sclerosis. When expressed in transgenic mice, mutant human cu,zn SOD causes progressive loss of motor neurons with consequent paralysis and death. Expression profiling of gene expression in SOD1-...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.1252
更新日期:2001-12-01 00:00:00
abstract::Antibody against acetylcholine receptor (AChR) of human skeletal muscle was measured using enzyme-linked immunosorbent assay and found in 23 (74%) of 31 Japanese patients with generalized myasthenia gravis. In 15 patients with generalized myasthenia gravis who had not undergone thymectomy and who were not receiving ad...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410150214
更新日期:1984-02-01 00:00:00
abstract::Four patients, aged 7-20 years, suffered from recurrent episodes of flaccid paralysis and encephalopathy associated with bilateral striatal necrosis and chronic progressive polyneuropathy. Using homozygosity mapping, a pathogenic missense mutation in the SLC25A19 gene that encodes the mitochondrial thiamine pyrophosph...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.21752
更新日期:2009-09-01 00:00:00
abstract::Although the cause of multiple sclerosis (MS) has remained obscure, many findings support an autoimmune pathogenesis on the background of a complex interaction between multiple genes and environmental factors. Accordingly, targeting the immune system has been a rational approach for the treatment of MS. The developmen...
journal_title:Annals of neurology
pub_type: 杂志文章,评审
doi:10.1002/ana.21289
更新日期:2007-10-01 00:00:00
abstract::We report on a new allele at the arylsulfatase A (ARSA) locus causing late-onset metachromatic leukodystrophy (MLD). In that allele arginine84, a residue that is highly conserved in the arylsulfatase gene family, is replaced by glutamine. In contrast to alleles that cause early-onset MLD, the arginine84 to glutamine s...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410310305
更新日期:1992-03-01 00:00:00
abstract::The prevalence of clinical signs and neuropathological findings of Alzheimer's disease (AD) is high in Down's syndrome (DS). In the general population, the apolipoprotein E (ApoE) epsilon 4 isoform is an important risk for AD. We studied the allelic frequencies of ApoE in 26 DS cases fulfilling clinical diagnostic cri...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410380215
更新日期:1995-08-01 00:00:00
abstract::Progressive cerebral deposition of amyloid-beta (Abeta) peptide, an early and essential feature of Alzheimer's disease (AD), is accompanied by an inflammatory reaction marked by microgliosis, astrocytosis, and the release of proinflammatory cytokines. Mucosal administration of disease-implicated proteins can induce an...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:
更新日期:2000-10-01 00:00:00
abstract::Pyruvate dehydrogenase deficiency is a major cause of primary lactic acidosis and neurological dysfunction in infancy and early childhood. Most cases are caused by mutations in the X-linked gene for the E1alpha subunit of the complex. Mutations in DLAT, the gene encoding dihydrolipoamide acetyltransferase, the E2 core...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.20550
更新日期:2005-08-01 00:00:00
abstract::An in vitro preparation has been developed in which epileptogenesis in mammalian central nervous system tissue may be studied. Addition of sodium penicillin to the medium bathing slices of guinea pig hippocampus induced epileptiform activity similar to that seen in hippocampal penicillin foci in vivo. Epileptiform eve...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410010510
更新日期:1977-05-01 00:00:00
abstract:OBJECTIVE:To identify novel autoantibodies for neuropathic pain (NeP). METHODS:We screened autoantibodies that selectively bind to mouse unmyelinated C-fiber type dorsal root ganglion (DRG) neurons using tissue-based indirect immunofluorescence assays (IFA) with sera from 110 NeP patients with various inflammatory and...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.25279
更新日期:2018-08-01 00:00:00
abstract:OBJECTIVE:Limited evidence is available to guide treatment of depression for persons with epilepsy. We evaluated the comparative effectiveness of sertraline and cognitive behavior therapy (CBT) for depression, quality of life, seizures, and adverse treatment effects. METHODS:We randomly assigned 140 adult outpatients ...
journal_title:Annals of neurology
pub_type: 杂志文章,随机对照试验
doi:10.1002/ana.25561
更新日期:2019-10-01 00:00:00
abstract::Disorders of neuronal migration in cerebral cortex are associated with neurological impairments, including mental retardation and epilepsy. Their causes and pathophysiology remain largely unknown, however. In patients with Zellweger disease, a lethal panperoxisomal disorder, and in mice lacking the Pxr1 import recepto...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:
更新日期:2000-09-01 00:00:00
abstract:OBJECTIVE:Reducing health and economic burdens from diagnostic delay of psychogenic nonepileptic seizures (PNES) requires prompt referral for video electroencephalography (VEEG) monitoring, the diagnostic gold standard. Practitioners make VEEG referrals when semiology suggests PNES, although few semiological signs are ...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.22345
更新日期:2011-06-01 00:00:00
abstract::Two families with a point mutation in mtDNA associated with myoclonic epilepsy and ragged-red fiber disease showed pronounced clinical heterogeneity. The mothers of the two families had adult-onset myopathy with ragged-red fibers, partial deficiency of cytochrome c oxidase, and sensory neuropathy. Members of the first...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410330613
更新日期:1993-06-01 00:00:00
abstract:OBJECTIVE:A number of hypotheses have been put forward as to why humans respond to fever by seizing. The current leading hypotheses are that respiratory alkalosis produces an as yet unidentified change in neural excitability or that inflammatory mediators potentiate excitatory synaptic transmission. However, it is well...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.21712
更新日期:2009-08-01 00:00:00
abstract::We report four children with idiopathic stroke syndromes who were assayed for human leukocyte antigen (HLA) class I markers and found to have HLA-B51 in common. This finding suggests that there may be a genetic predisposition for "idiopathic" childhood stroke, and host factors, possibly in concert with environmental f...
journal_title:Annals of neurology
pub_type: 杂志文章
doi:10.1002/ana.410310618
更新日期:1992-06-01 00:00:00