摘要:Ketones may bypass the defect in complex I activity implicated in Parkinson di sease (PD). Five of seven volunteers with PD were able to prepare a “hyperketog enic”diet at home and adhere to it for 28 days. Substituting unsaturated for sa turated fats appeared to prevent cholesterol increases in four volunteers.Unifie d Parkinson’s Disease Rating Scale scores improved in all five during hyperketo nemia, but a placebo effect was not ruled out.
摘要:Objective: We have investigated whether central activation failure (CAF) is in creased during local muscle fatigue in chronic fatigue syndrome (CFS). Methods: Fourteen female CFS patients and 14 age matched healthy female controls made a 2 min sustained maximal voluntary contraction (MVC) of the biceps brachii muscle . Before, during, and after sustained MVC, electrical endplate stimulation was a pplied. Force and 5 channel surface EMG (sEMG) were registered. Results: Althoug h force responses upon stimulation during rest did not differ between patients a nd controls, MVC was significantly lower in patients. Already at the beginning o f sustained MVC, CFS patients showed significantly larger CAF than controls (36. 5±17.0%and 12.9±13.3%, respectively). For all individual patients mean CAF o ver the first 45 s was higher than 30%, while it was below 30%for all controls . Less peripheral fatigue in patients was demonstrated by the changes in muscle fibre conduction velocity and the differences between force responses before and after contraction. Conclusions: Central activation is diminished in CFS patient s. Possible causes include changed perception, impaired concentration, reduced e ffort and physiologically defined changes, e.g. in the corti cospinal excitabil ity or the concentration of neurotransmitters. As a consequence, demands on the muscle are lower, resulting in less peripheral fatigue. Significance: CFS patien ts show reduced central activation during MVC. The underlying pathophysiological processes remain still to be determined.
摘要:Objective: To investigate the effects of hyperglycemia on axonal excitability in human diabetics. Diabetic nerve dysfunction is partly associated with the alt ered polyol pathway and Na+ K+ATPase activity, probably resulting in a decrea se in the transaxonal Na+gradient and reduced nodal Na+currents. Methods:Thres hold tracking was used to measure the relative refractory periods (RPs) of media n motor axons in 58 diabetic patients, 45 normal subjects, and 12 patients with non diabetic axonal neuropathy. In diabetic patients, the relationship of RPs w ith hemoglobin A1c (HbA1c) levels was analyzed. Results: The mean RP was similar for diabetics and normal controls as a group, but was longer in patients with n on diabetic neuropathy than in normal controls (P=0.02). Diabetic patients with good glycemic control (HbA1c levels < 7%) had longer RPs than patients with po orer glycemic control and normal controls (P=0.01). RP was longest at the HbA1c level of 6%, gradually decreasing and reaching a plateau at the HbA1c level of 8 9%. Conclusions: Hyperglycemia shortens RPs, possibly because metabolic abno rmalities lead to reduced nodal Na+currents, and thereby to a lower inactivatio n of Na+channels when generating an action potential. Significance: RP measurem ents could provide new insights into the ionic pathophysiology of human diabetic neuropathy.
摘要:A 30-year-old white man presented with a sporadic form of gradually progress ive spastic gait and, later, supranuclear vertical and horizontal gaze palsy, mi ld cognitive impairment, loss of postural reflexes, and falls. DNA analysis reve aled H1/H1 haplotype without tau gene (exons 9 to 13) mutation. Eight years late r, postmortem revealed a tauopathy similar to progressive supranuclear palsy. Un usual aspects were early age at onset, neurofibrillary tangle, and tau involveme nt of the cord.
摘要:Objective: To assess the effects of focal motor cortex stimulation on motor pe rformance and cortical excitability in patients with Parkinsons disease (PD). Methods: Repetitive transcranial magnetic stimulation (rTMS) was performed on th e left motor cortical area corresponding to the right hand in 12 offdrugpati ents with PD. The effects of subthreshold rTMS applied at 0.5 Hz (600 pulses) or at 10 Hz (2000 pulses) using a realor a shamcoil were compared to those obtained by a single dose of l dopa. The assessment included a clinical evalua tion by the Unified Parkinsons Disease Rating Scale and timed motor tasks, and a neurophysiological evaluation of cortical excitability by single and paired pulse TMS techniques. Results:RealrTMS at 10 or0.5 Hz, but notshamstim ulation, improved motor performance. High frequency rTMS decreased rigidity and bradykinesia in the upper limb contralateral to the stimulation, while low fre quency rTMS reduced upper limb rigidity bilaterally and improved walking. Concom itantly, 10 HzrTMS increased intracortical facilitation, while 0.5 HzrTMS restor ed intracortical inhibition. Conclusions: Low and highfrequency rTMS of the pri mary motor cortex lead to significant but differential changes in patients with PD both on clinical and electrophysiological grounds. The effect s on cortical excitability were opposite to previous observations made in health y subjects, suggesting a reversed balance of cortical excitability in patients w ith PD compared to normals. However, the underlying mechanisms of these changes remain to determine, as well as the relationship with clinical presentation and response to l dopa therapy. Significance: The present study gives some clues to appraise the role of the primary motor cortex in PD. Clinical improvement induc ed by rTMS was too short lasting to consider therapeutic application, but these results support the perspective of the primary motor cortex as a possible targe t for neuromodulation in PD.
摘要:Objective: To explore the role of abnormal neuronal activity in the basal gang lia and thalamus in the generation of dystonia. Methods: Microelectrode recordin g was performed in the globus pallidus internus (GPi), ventral thalamic nuclear group ventral oral posterior/ventral intermediate, Vop/Vim) and subthalamic nucl eus (STN) in patients with primary dystonia (n=11) or secondary dystonia (n=9) d uring surgery. Electromyogram (EMG) was simultaneously recorded in selected musc le groups. Single unit analysis and cross correlations were carried out. Result s: Three hundred and sixty seven neurons were obtained from 29 trajectories (GP i: 13; Vop/Vim:12; STN: 4), 87%exhibited altered neuronal activity including gr ouped discharges in GPi (n=79) and STN (n=37), long lasting neuronal activity ( n=70) and rapid neuronal discharge (n=86) in Vop/Vim. There were neurons in Vop, GPi and STN firing at the same frequency as EMG during dystonia (mean: 0.39 Hz, range 0.12-0.84 Hz). Significant correlations between neuronal activity and EM G at the frequency of dystonia were obtained (GPi: r2=0.7 (n=31), Vop/Vim: r2=0. 64 (n=18) and STN: r2=0.86 (n=17)). Conclusions: Consistent with previous findin gs of abnormalities observed in Vop/VIM and GPi in relation to dystonia, the pre sent data further show that the altered activity in GPi, specifically in dorsal subregions of GPi, Vop/Vim and STN is likely to be directly involved in the prod uction of dystonic movement. Dystonia related neuronal activity observed in mot or thalamus and basal ganglia nuclei of GPi and STN indicates a critical role of their interactions affecting both indirect and direct pathways in the developme nt of either generalized or focal dystonia. Significance: These data support a c entral role of the basal ganglia in producing dystonic movements.
摘要:Objective: To find out whether 14 16 year old pupils with visual perception disabilities have atypical EEG activation patterns during visual discrimination . Methods: EEG correlation indices (EEGCIs), based on the waveform characteristi cs of two EEG signals, were used as measures of slow joint activation of cortica l regions during visual discrimination in pupils with visual perception disabili ties. Results: During visual discrimination low EEGCIs were seen between the lef t temporal and both parieto occipital EEG channels in pupils with visual percep tion disabilities and in pupils with a poor occupational outcome. The pupils wit h low performance intelligence and those with difficulties in the visual discrim ination task had low EEGCIs within the left hemisphere. The left hemispheric dom inance of the findings is suggested to reflect the psychophysiology of the task since visual discrimination demands attention to details (local processing) and is thus supposed to be more strongly represented in the left hemisphere. Conclus ions: During visual discrimination, low EEGCIs were seen in the posterior and le ft hemispheric regions of pupils with disabilities in visual perception and visu al discrimination and with a poor occupational outcome. Significance: Low EEGCIs in posterior and left hemispheric regions during visual discrimination can to s ome extent be seen as neurophysiological markers for visual perception disabilit ies and a poor occupational outcome and imply an increased need for adjustment o f the educational curriculum and a need for occupational guidance.
摘要:Objective: To find out whether 14 16 year old reading and writing impaired pu pils have atypical EEG activation patterns during reading. Methods: EEG correlat ion indices (EEGCIs), based on the waveform characteristics of twoEEG signals, w ere used as measurers of slow joint activation of cortical regions during readin g in pupils with reading and writing impairment. Results: Reading was associated with high EEGCIs within the right hemisphere in reading and writing impaired pu pils. The finding is analogous to the results of an earlier study [Byring, Elec t roencephalogr. Clin. Neurophysiol. 63 (1986) 1] in boys with spelling disabilit i es. The activation in the right hemisphere might represent a compensation for a left hemisphere dysfunction in pupils with reading and writing impairment during reading, as suggested by a number of functional neuroimaging studies. T his interpretation was corroborated by high EEGCIs especially in those impaired pupils who had a good occupational outcome. Conclusions: EEGCIs during reading a re high within the right hemisphere in pupils with reading and writing impairmen t. Significance: High EEGCIs within the right hemisphere during reading might be considered neurophysiological markers for reading and writing impairment.
摘要:Frontotemporal dementia(FTD) often coexists with motor neuron disease(MND). To characterize glucose hypometa- bolism in patients with FTD with MND (FTD/MND), the authors compared the glucose metabolism of 8 patients with FTD/MND with that of 29 patients with FTD. All of the patients with FTD/MND showed glucose hypometabolism only in the frontal a rea, whereas most patients with FTD had hypometabolism in the frontal and tempor al areas. FTD/MND also showed a more symmetric pattern of glucose hypometabolism than FTD.
摘要:Objective: To test the hypothesis that the N10 far field potential in median nerve somatosensory evoked potentials is generated by the motor axons by examini ng patients with amyotrophic lateral sclerosis (ALS). Methods: Subjects were 5 A LS patients showing pronounced or complete denervation of median inner vated s mall hand muscles. We evaluated N10 over scalp, and proximal plexus volleys (PPV s) at lateral or anterior cervical electrode. Results: N10 and PPVs were definit ely preserved for every ALS subject. N10 amplitudes of ALS subjects were even si gnificantly larger than control subjects. In one ALS patient completely lacking motor axons, N10 was larger than the largest one among control subjects. Conclus ions: Present results clearly indicate that N10 is not predominantly generated b y motor axons but by the whole median nerve dominated by sensory axons. We propo se a theory that N10 is a junctional potential generated by the entrance of the median nerve into bone at the intervertebral foramen, producing a positive pole at the non cephalic reference electrode. Significantly larger N10 in ALS subjec ts may be due to the lack of cancellation by slower motor axons. Significance: T he hypothesis that N10 is generated by motor axons is refuted, and a new theory of its generation is presented.
摘要:The clinical diagnosis of Marchiafava Bignami disease (MBD) has con siderably changed during recent decades with brainMRI providing the opportunity of a reliable in vivo diagnosis. Howe ver, semiologic and neuroimaging characteristics of the currently known spectrum of MBD have not been investigated systematically, and knowledge of clinicoradio logic associations is sketchy. We report an illustrative case with limited callo sal involvement on MRI and a favorable outcome and have reviewed literature on c linical and radiologic features in 50 cases of MBD diagnosed in vivo since 1985. Our reviewed data suggest the differentiation of two clinicoradiologic subtypes : Type A is characterized by major impairment of consciousness, T2 hyperintense swelling of the entire corpus callosum on early MRI and poor outcome. Type B sh ows at most slight impairment of consciousness, partial callosal lesions on MRI and a favorable outcome. Differentiation of these clinicoradiologic subtypes may help resolve inconsistencies of the established clinical classification resulti ng from new insights into the clinical course and prognosis of MBD by structural neuroimaging.
摘要:Mutations in the epsilon-sarcoglycan gene (SGCE) are associated with familial myoclonus dystonia, but the full spectrum of the phenotype may not be fully def ined. We screened 58 individuals with a range of myoclonic/dystonic syndromes fo r SGCE mutations. We found mutations (four of them novel) in six (21%) of the 2 9 patients with essential myoclonus and myoclonic dystonia, but did not find mut ations in the 29 patients with other phenotypes.
摘要:Background and purpose: Carotid angioplasty and stenting, a so far non valida ted procedure, may be an alternative to surgery in patients with a high surgical risk. However, it carries also a risk of cerebral embolic events. The purpose o f this study was to evaluate tissue signal abnormalities in the brain before and after carotid angioplasty and stenting by means of diffu sion (DWI) and perfu sion (PWI) weighted magnetic resonance imaging (MRI). Methods: We performed cere bral MRI before and after carotid angioplasty in 22 consecutive patients, with 2 3 treated high grade carotid stenoses. The lesions were located at the origin o f the internal carotid artery (ICA) in 20 patients, and at the origin of the com mon carotid artery (CCA) in 2. MRI was performed the day before, and repeated wi thin 24 hours after the procedure, and examined by two neuroradiologists. Result s: All stent implantations were successful but 4 patients developed an acute neu rological deficit within 24 hours after carotid angioplasty. On PWI, Time To Pea k (TTP) values ipsilateral to the carotid stenosis were increased before the pro cedure in 15 patients, and had remained normal in 6 and were not assessable in 1 . After the procedure, TTP values were normal in 12 patients, increased in 8 and not assessable in 2. On DWI, new ipsilateral lesions were detected in 2 patient s: 1 with an acute neurological deficit and 1 symptom free. Conclusion: Perfusio n deficits may be present in severe carotid stenosis and be improved within 24 h ours by carotid angioplasty and stenting. Asymptomatic infarcts may occur.
摘要:Three related patients from Colombia presented with a juvenileonset neuronal c eroid lipofuscinosis. Electron microscopy of one case showed condensed fingerpri nt profiles, and genetic analyses identified a novel missense mutation in CLN5. The authors demonstrate the existence of pathogenic CLN5 mutations outside north ern Europe and that mutations in this gene can lead to an atypical late-onset n euronal ceroid lipofuscinosis disease, in addition to the late infantile form fi rst described inFinland.
摘要:Silver syndrome (SS) is a complicated form of hereditary spastic paraplegia as sociated with distal wasting of the small muscles of the hands. We have previous ly described a large kindred with SS and mapped a genetic locus (SPG17) to chrom osome 11q12 q14. In the current study we analyse the clinical phenotype and per form linkage analysis in three new SS families. In addition we analyse candidate genes mapping to the SS locus (SPG17). Clinical assessments were performed on 2 5 (15 affected) individuals from each family in which SS segregates with variabl e clinical expression. Neurophysiological studies, performed in the index case o f two families, suggested anterior horn cell or nerve root involvement. Linkage analysis using microsatellite markers mapping to the SPG17 locus was performed a nd only one of the three families had a microsatellite segregation pattern compa tible with linkage. Candidate genes mapping to the SS critical region were analy sed in this and one other SPG17 linked family. Mutation analysis of genes encodi ng calpain 1 (CAPN1), copper chaperone for superoxide dismutase (CCS), ADP ribos ylation factor like 2 (ARL2), LOC120664, a putative homologue of atlastin (ATLS TL 1) and sorting nexin 15 (SNX15) failed to identify any disease specific mut ations. SS therefore exhibits both clinical and genetic heterogeneity and the SP G17 locus may account for a significant proportion of SS mutations in the UK.
摘要:Objective: To identify lateralizing features during seizures in infants and as sess their reliability. Methods Infants were included if they had video EEG mon itoring at our institution, and were seizure free for at least 12 months after epilepsy surgery. Lateralizing signs and seizure symptomatology were classified based on blinded video review. Results We analyzed 100 seizures from 19 infants (1 to 32, mean 13 months of age) (1 to 14 seizures per patient). Potential later alizing signs were seen in 58 seizures from 12 infants, including unilateral clo nic jerking (8 patients); forced, sustained tonic version of the eyes to one sid e (7 patients); predominantly unilateral infantile spasms (5 patients); unilater al tonic stiffening of an arm and leg (2 patients); nystagmus (2 patients) and p ostictal hemiparesis (1 patient). Except for tonic eye version, each of the sign s was contralateral to the hemisphere of seizure onsetin all but one patient wh o had predominantly ipsilateral spasms and clonic arm activity. Tonic eye versio n was contralateral in 3 patients, ipsilateral in 1 patient, and toward either s ide in different seizures in 3 patients. Conclusion Reliable lateralizing signs included focal clonic activity and predominantly unilateral spasms. Focal tonic activity, nystagmus and postictal hemiparesis were also consistently contralater al but were observed only in few patients. Tonic eye version was unreliable and could not beused to lateralizeseizure onset. The sequence of eye and head version evolvi ng to generalized tonic clonic convulsions was not seen in this age group.
摘要:The pathogenic mechanisms underlying Batten disease are unclear. Patients unif ormly possess autoantibodies against glutamic acid decarboxylase (GAD) that are predominantly reactive with a region of GAD (amino acids 1 to 20) distinct from subjects with autoimmune type 1 diabetes or stiff-person syndrome.Batten patien ts did not possess autoantibodies against other type 1 diabetes-associated auto antigens and human leukocyte antigen genotypes revealed no specific associations with this disease.
摘要:Children undergoing surgery with infant-onset epilepsy were classified into t hose with medically refractory infantile spasms(IS), successfully treated IS, an d no IS history, and the groups were compared for pre-and postsurgery clinical and Vineland Ad aptive Behavior Scale (VABS) developmental quotients(DQ). Children without an IS history were older at surgery and had longer epilepsy durations than those with IS despite similar substrates, surgeries, and seizure frequencies. In all group s, better postsurgery VABS-DQ scores were associated with early surgical interv ention indicating that infant-onset epilepsy patients with or without IS are at risk for seizure-induced encephalopathy.
摘要:A linkage and association of the CD45 (protein tyrosine phosphatase, receptor type C) C77G polymorphism and multiple sclerosis (MS) has been found in some s tudies but not in others. We analysed the C77G polymorphism in MS patients from the genetically homogeneous population of Sardinia. Using the ransmission disequ ilibrium test, the mutation has been sought in 241 patients and 217 healthy sibs (HS) from singleton MS families and it was found in 5 (2.07%) affected and 3 ( 1.38%) HS from 7 heterozygous parents (1.45%). Transmission of the G77 allele was 71.4%(TDT = 1.3, P = 0.26) in patients and 50%(TDT = 0, P = 1) in HS. Str atifying families according to carriage of MS predisposing (DR+) or not predi sposing(DR ) HLA DR DQ genotype in patients, percentage of G77 transmission t o DR+patients was 33 (TDT = 0.33, P = 0.56, Pc = 1.12), while it was 100 (TDT = 4, P = 0.045, Pc = 0.09) in the DR patients. We concluded that, despite the pr esence of CD45 G77 polymorphism in a few patients who did not carry the HLA DR DQ MS predisposing molecules, CD45 did not contribute to development of the d isease in Sardinian MS.
摘要:The authors report a 35-year-old man whose unilateral cerebellar lesion resu lted in marked deficits in coordinating simultaneous cyclic movements of the arm and leg on his ipsilesional side. He exhibited no such deficits when making sim ultaneous movements of the contralesional limbs or when moving paired left and r ight limbs. Thus, the cerebellum,which is already known to underlie within-limb interjoint coordination,also contributes to coordination between limbs.
摘要:A real time quantitative PCR (QPCR) method using TaqMan technology was used to assess the copy number of the two survival motor neuron genes (SMN1 and SMN2) o n chromosome 5q13. This allows the accurate determination of carriers for spinal muscular atrophy (SMA), with one copy of SMN1. Analysis of 569 normal southern Chinese individuals revealed a carrier incidence of 1.6%, similar to that found in the western society. Study of 42 obligatory carriers showed a (2 +0) genoty pe in two (4.8%). In 27 SMA patients with homozygous deletion of the SMN1 gene, the number of SMN2 gene correlated with disease phenotype, with 68%of t ype II and III patients carrying three or more SMN2 genes, whilst the incidence of three or more SMN2 genes in the normal population was 1.57%.
摘要:The authors reviewed the occurrence and concomitant factors of laryngospasm in X-linked spinobulbar muscular atrophy(Kennedy disease [KD]).Recurrent laryngos pasm was observed in 47%of 49 patients with KD, but in only 2%of a control gro up of patients with early-stage ALS.
摘要:Objective: To investigate the long-term differential drug effects on cognitiv e functioning in school-aged children exposed to antiepileptic drugs (AEDs) in utero. Methods: Mothers with epilepsy were recruited from specialist epilepsy cl inics and obstetric clinics from the Liverpool and Manchester region. The mother s and their children were recruited without prior knowledge of their AED treatme nt during pregnancy or the health of the offspring. A battery of neuropsychologi cal tests was applied to each mother-child pair in order to obtain a neuropsych ological profile for each child. Results: Neuropsychological investigation was p erformed on 249 children between the ages of 6 and 16. Children exposed to sodiu m valproate had a significantly lower verbal IQ when compared to children expose d to other antiepileptic drugs or not exposed at all. The same children were mor e likely to have an IQ below 69 and more likely to have memory impairment when c ompared to the othergroups. The mothers’IQ, exposure to sodium valproate, and t he number of tonic-clonic seizures during pregnancy were significant predictors of verbal IQ in this population. Conclusions:This retrospective study highlights the potential harmful effects of sodium valproate exposure in utero on neuropsychological development.
摘要:Most patients admitted for inpatient rehabilitation find it beneficial even wh en there is little change in physical disability. The aim of this study was to d etermine the characteristics of patients who felt that they had not benefited fr om inpatient rehabilitation and to delineate the underlying reasons for this per ception. From a database of 331 patients admitted to a neurological rehabilitati on unit over a three year period, we ascertained those with a low score < 5) on a self rated visual analogue scale (VAS) regarding their perception of the ben efit of rehabilitation. We investigated their disability outcomes, aspects of th e rehabilitation process through analysis of integrated care pathways, and from inspection of the multidisciplinary record identified specific adverse factors w hich might contribute to dissatisfaction. Low VAS scores were detected in 6%of patients (n = 19). These did not correlate with baseline demographic factors or disability levels, but were associated with unresolved external problems regardi ng community care and accommodation, and conflicts between patients and therapis ts. We conclude that from the patientsperspective, successful inpatient rehabi litation depends on adequate attention given to community based issues and heal th care professionals recognising patientsneeds. When these two conditions are not fulfilled, patients are more likely to express a lack of satisfaction with their rehabilitation.
摘要:Objective: To report the frequency of major malformations in lamotrigine-expo sed pregnancies from September 1, 1992,through March 31, 2004, in the Internatio nal Lamotrigine Pregnancy Registry.Methods: Health care professionals throughout the world can voluntarily enroll lamotrigine-exposed pregnancies in this obser vational study. Only pregnancies with unknown outcomes at the time of enrollment were included in the analysis. The percentage of outcomes with major birth defe cts was calculated as the total number of outcomes with major birth defects divi ded by the sum of the number of outcomes with major birth defects +the number o f live births without defects. Results: Among 414 first-trimester exposures to lamotrigine monotherapy, 12 outcomes with major birth defects were reported (2.9 %, 95%CI 1.6%to 5.1%). Among the 88 first-trimester exposures to lamotrigin e polytherapy including valproate, 11 outcomes with major birth defects were rep orted(12.5%; 95%CI 6.7%to 21.7%). Among 182 first-trimester exposures to la motrigine polytherapy excluding valproate, 5 outcomes with major birth defects w ere reported (2.7%, 95%CI 1.0%to 6.6%). No distinctive pattern of major birt h defects was apparent among the offspring exposed to lamotrigine monotherapy or polytherapy. Conclusions: The risk of all major birth defects after first-trim ester exposure to lamotrigine monotherapy(2.9%) was similar to that in the gene ral population and in other registries enrolling women exposed to antiepileptic monotherapy (3.3%to 4.5%). However, the sample size was too small to detect an y but very large increases in specific birth defects.
摘要:Tau gene mutations with insoluble Tau neuropathology have been identified in p edigrees with frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP 17). Other neurodegenerative diseases, including progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), are also characterised by inso luble Tau neuropathology. This study sought to determine the nature and frequenc y of tau gene mutations in an affected proband cohort of patients within this sp ectrum of neurodegenerative diseases. Sixty four individuals with clinical feat ures consistent with FTD and other tauopathies were referred over a three year p eriod. There was neuropathological confirmation of disease in 30%. Individuals were screened for mutations in the coding region and flanking intronic regions of the tau gene by direct sequencing of PCR products. Four confirmed tau gene mutations were identified representing 6.3%for the total affected proband cohor t. Tau gene mutations were found in three of twelve (25%) of the cases with a f amily history of dominantly inherited frontotemporal dementia, but in only one o f 25 cases without a family history (4%). Although tauopathies have been consid ered to result from genetic defects, screening for tau gene mutations in sporadi c cases is not likely to identify pathogenic mutations.
摘要:Objective: To determine the rate of occurrence of major malformations in infan ts whose mothers had taken the drug valproicacid (VPA) as monotherapy during the first trimester of pregnancy and had enrolled in the North American Antiepilept ic Drug Pregnancy Registry. Methods: Data were collected from pregnant women throughout the United States and Canad a through telephone-based interviews. Each woman was interviewed at enrollment, at 7 months’gestation, and postpartum.With her written permission, the medical records of each mother and her infant were obtained. The major malformations ta bulated were those identified at or before 5 days of age. The prevalence of cong enital malformations among offspring of monotherapy VPA-exposed women was compa red with that among infants of women exposed to all other antiepileptic drugs(in ternal comparison group) and with that among newborns in the Active Malformation s Surveillance Program at Brigham and Women’s Hospital (external comparison gro up). Results:Sixteen affected cases were identified among 149 VPA-exp- osed women (proportion: 10.7%; 95%CI: 6.3 to 16.9%). The prevalence in the internal comparison group was 2.9%(95%CI:2.0 to 4.1%; odds ratio: 4.0, 95%CI : 2.1 to 7.4; p < 0.001). Assuming a 1.62%prevalence in the external comparison group, the relative risk of having an affected offspring for VPA exposed women was 7.3 (95%CI: 4.4 to 12.2; p < 0.001).Conclusion: Maternal exposure to valpro ic acid during the first trimester of pregnancy significantly increased the risk of major malformations.
摘要:Troyer syndrome, originally described in 1967 in an Old Order Amish population , is a complicated form of hereditary spastic paraplegia (HSP) inherited in an a utosomal recessive fashion and slowly progressive. The cardinal features are spa stic paraparesis, pseudobulbar palsy and distal amyotrophy, together with mild d evelopmental delay and subtle skeletal abnormalities. We report a detailed evalu ation of 21 cases of Troyer syndrome in the same Amish population, including thr ee from the original study. Imaging of the brain revealed white matter abnormali ties, particularly in the temporoparietal periventricular area. This study, coup led with the recent identification of the gene responsible (SPG20, encoding spar tin), increases our understanding of this form of HSP.
摘要:Background: Autosomal dominant optic atrophy (ADOA) is the commonest form of i nherited optic neuropathy. Mutations in the OPA1 gene encoding a dynamin-relate d mitochondrial protein underlie ADOA and may perturb the biogenesis and mainten ance of mitochondria. Objective: To investigate the mutation spectrum of the OPA 1 gene and assess alterations in mitochondrial content caused by OPA1 mutations. Methods:Sixteen Korean patients with clinically suspected ADOA were studied. Th e mutation spectrum of the OPA1 gene was analyzed by PCR single-strand conforma tion polymorphism and sequencing, and mitochondrial DNA (mtDNA) content was quan tified by real-time PCR. Results: Eight different mutations were found, includi ng five novel mutations. Quantitative real-time PCR analysis showed excellent l inearity and precision for the determination of mtDNA copy numbers. The number o f mtDNA copies per cell in patients with OPA1 gene mutations(ages 7 to 40) was s ignificantly lower than those in all normal control subjects (p=0.037), particul arly lower than in normalcontrol subjects ages 10 to 39 (p=0.022). Conclusion: T he mutation spectrum of the OPA1 gene disclosed marked genetic heterogeneity and the mitochondrial DNA content was found to be lower in autosomal dominant optic neuropathy, which provides direct evidence for a pathogenetic role of mutations of the OPA1 gene.
摘要:Activated myelin specific T cells are thought to mediate inflammatory tissue damage in multiple sclerosis (MS). Applying a large panel of myelin antigens, we demonstrate the direct ex vivo detection of viable IFN γ/TNF αproducing CD4 +/CD69+T cells 6 hours after antigenic challenge, by intracellular flow cytome try in 3/33 MS patients and 2/26 healthy controls with calculated frequencies of (mean ±.SEM): 0.031%±0.002%versus 0.037%±0.029%. By comparison, the rece ntly developed IL 7 modified proliferation assay revealed i) a higher number of individuals showing myelin reactivity (17/37 MS patients and 12/24 healthy indi viduals) and ii) a significant difference in the response to myelin basic protei n (MBP) between the two groups in a longitudinal analysis, indicating a higher a ctivity of myelin specific T cells in MS patients. Our data provide new perspec tives in detecting pathogenetically relevant T cells, but clearly demonstrate th e different conclusions which must be drawn from various approaches concerning t he quantification of autoreactive T cells.