Factors affecting the diagnostic delay in amyotrophic lateral sclerosis

Background

Although amyotrophic lateral sclerosis (ALS) is a relentlessly progressive disorder, early diagnosis allows a prompt start with the specific drug riluzole and an accurate palliative care planning. ALS at onset may however mimic several disorders, some of them treatable (e.g., multifocal motor neuropathy) or epidemiologically more frequent (e.g., cervical myelopathy).

Objective

To study the delay from onset to diagnosis in a cohort of ALS patients and to the variables that may affect it.

Methods

We performed a retrospective analysis of the diagnostic delays in a cohort of 260 patients affected by ALS (M/F = 1.32) followed at our tertiary referral ALS Center between 2000 and 2007.

Results

The median time from onset to diagnosis was 11 months (range: 6–21) for the whole ALS cohort, 10 months (range: 6–15) in bulbar-onset (n = 65) and 12 months (range: 7–23) in spinal-onset (n = 195) patients (p = 0.3). 31.1% of patients received other diagnoses before ALS and this led to a significant delay of the correct diagnosis in this group (other diagnoses before ALS, n = 81: median delay, 15 months [9.75–24.25] vs ALS, n = 179, median delay, 9 months [6–15.25], p < 0.001).

Conclusions

The diagnostic delay in ALS is about one year, besides the growing number of tertiary centres and the spread of information about the disease through media and internet. Cognitive errors based on an incorrect use of heuristics might represent an important contributing factor. Furthermore, the length of the differential diagnosis from other disorders and delays in referral to the neurologist seems to be positively associated with the delay in diagnosis.     

Bandpass filter settings differentially affect measurement of P50 sensory gating in children and adults

Objective

This study investigated the effect of four different bandpass filter settings on measures of the P50 component and the signal-to-noise ratios (SNR) of averaged ERPs obtained from a sensory gating paradigm employing paired-click stimuli.

Methods

Participants were adults (n = 18) 20–55 years old and children (n = 25) 5–10 years old who were free of neurological disorders.

Results

Results show that the filter settings (0.23–75 Hz, 10–50 Hz, 10–75 Hz, and 10–200 Hz) differentially affected the P50 amplitude, noise power and SNR measures of the conditioning and test clicks, and P50 T/C ratios.

Conclusions

The 10–50 Hz filter setting may be optimal in studies that include only adults as these settings resulted in the smallest mean P50 T/C ratio, a reasonable standard deviation (SD) for the ratio, and the highest SNRs. The 10–200 Hz filter may be the best for studying young children as this setting had the smallest mean and SD of P50 T/C ratios for these participants.

Significance

In studies that include both adults and children investigators are advised to use the 10–200 Hz filter setting because the smaller variability of sensory gating in the child group helps ensure better homogeneity of variance measures between the groups.     

Anti-aquaporin-4 antibody in Chinese patients with central nervous system inflammatory demyelinating disorders

Objective

To determine seroprevalence of aquaporin-4 (AQP4) antibody in Chinese patients with central nervous system (CNS) inflammatory demyelinating disorders.

Methods

AQP4 antibody was detected by anti-AQP4 antibody assay. We measured seroprevalence in 200 patients with neuromyelitis optica (NMO, n = 44), multiple sclerosis (MS, n = 46), transverse myelitis (TM, n = 44), optic neuritis (ON, n = 13), acute disseminated encephalomyelitis (ADEM, n = 2), and other neurological diseases (OND, n = 51).

Results

AQP4 antibody seropositivity was 88.6% in patients with NMO, 4.3% in patients with MS, 30.8% in patients with ON and 51.7% in patients with LETM (longitudinally extensive TM). No patients with acute partial TM, ADEM, OND were positive for AQP4 antibody. Sensitivity of the test was 88.6% (95% CI 80–95) in patients with NMO. Specificity is 97.9% (95% CI 95.1–100) in 46 MS patients, with 51 OND patients as the control group. If the patients with recurrent ON, LETM were considered high risk for NMO (n = 37) and the remaining patients (n = 119) were considered controls, the sensitivity of this assay would be 48.6% (95% CI 33.4–64.1) and the specificity 97.5% (95% CI 94.7–100).

Conclusion

This study confirms that AQP4 antibody is a sensitive and specific biomarker for discrimination between NMO and other CNS autoimmune diseases.     

Altered antioxidant defense system in clinically stable patients with schizophrenia and their unaffected siblings

Objective

To determine Red Blood Cell (RBC) antioxidant enzyme activities and plasma Thiobarbituric Acid Reactive Substances (TBARS) in clinically stable patients with schizophrenia and their unaffected siblings.

Methods

A case-control study carried out on three groups: 60 schizophrenic patients treated with neuroleptics, 33 of their unaffected siblings and 30 healthy controls with no family psychiatric history. Biological markers were measured on fasting patients after a period of tobacco abstinence: RBC antioxidant enzyme activities – superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) – by spectrophotometry and plasma levels of TBARS by spectrofluorimetry.

Results

RBC SOD and CAT activities were significantly lower in schizophrenic patients and their unaffected siblings compared to the control group (P < 0.001). Schizophrenic patients also had significantly lower RBC GSH-Px activity than controls (P = 0.03), whereas their unaffected siblings had significantly higher RBC GSH-Px activity than controls (P = 0.04). Plasma TBARS were higher in schizophrenic patients than their unaffected siblings: 2.1 ± 0.8 μmol/l vs. 1.7 ± 0.6 μmol/l (P = 0.06).

Conclusions

Our results showed a decrease in antioxidant enzyme activities and an increase in lipid peroxidation confirming the existence of oxidative stress in schizophrenic patients treated with neuroleptics. Additionally, this suggests that the increase in GSH-Px activity in unaffected siblings would be a protective mechanism against oxidative stress and damage. Other studies are necessary to confirm these findings.     

Motor unit firing in amyotrophic lateral sclerosis and other upper and lower motor neurone disorders

Objective

Motor unit recruitment order and firing rate was investigated in healthy subjects, and in small numbers of patients 50 years ago. We aimed to investigate firing rate in different disorders, testing the same target muscle with normal strength, to evaluate possible application in diagnosing upper motor neuron (UMN) lesion.

Methods

We studied motor unit firing in the tibialis anterior muscle in six groups of subjects; normal subjects (n = 45), patients with amyotrophic lateral sclerosis (ALS) (n = 36), primary lateral sclerosis (PLS) (n = 21), progressive muscular atrophy (PMA) (n = 14), various upper motor neurone lesions (n = 16) and polyneuropathy (n = 42). In all these subjects the tibialis anterior muscle was of normal strength. Motor units were recruited during slight contraction in order to study 2–5 motor units at each recording site, using a standard concentric needle electrode, so that 20–22 motor units were recorded in each muscle. We analysed the coefficient of variation (CV) for amplitude, area, duration and firing rate in these motor units, and the correlation between motor unit potential size and recruitment order.

Results

The mean MU firing rate in this task was similar in each group. No recruitment order was disclosed within the limits of the study task. The CV of firing rate was decreased in UMN and PLS groups. ALS patients with marked spasticity showed a lower CV of motor unit firing rate. The CV of amplitude, area and duration was similar between groups.

Conclusions

These results in tibialis anterior indicate that physiological modulation of lower motor neuron (LMN) firing rate is decreased in patients with lower limb spasticity. The variability of MU discharges tends to be greater in diseases affecting the LMN.

Significance

These results suggest that, notwithstanding the simplicity of the task we have used, the physiological variability of motor unit firing may be a useful variable in assessing UMN involvement in motor system disorders.     

Systemic arterial inflammation, measured with 18FDG-PET, is common amongst subjects with both recent and prior cerebrovascular disease

Objective

To compare systemic arterial inflammation in subjects with recent ischaemic stroke or TIA and controls with prior cerebrovascular disease.

Methods

Systemic arterial inflammation was prospectively measured by ¹⁸F-fluorodeoxygluose positron emission tomography in 11 cases with recent ischaemic stroke or TIA, and 11 sex matched controls with prior cerebrovascular disease.

Results

Hot spots (both carotid and non-carotid) of localised ¹⁸FDG uptake were found in more than half of all patients with either recent (n = 6) or prior (n = 8) cerebrovascular disease. There was no significant difference in the total number of hotspots, or hotspots at specific sites, in cases compared with controls. Mean standard uptake values (SUV) were similar in the carotid arteries and aorta of cases and controls, and showed a trend toward higher values in the femoral arteries of the controls (median 1.8; IQR 1.6–2.2) compared to cases (median 1.5; IQR 1.4–1.7).

Conclusion

Arterial inflammation was common, and appeared similar, in patients with recent stroke/TIA, and controls with stroke/TIA more than two years previously.     

Is mechanical ventilation associated with intraventricular hemorrhage in preterm infants?

Background

The impact of mechanical ventilation on the incidence of intraventricular hemorrhage (IVH) in very low birth weight (VLBW) infants is unknown, simply because the vast majority of these infants have been routinely intubated and mechanically ventilated. There is a growing interest in the use of early nasal continuous positive airway pressure (ENCPAP) and avoiding mechanical ventilation.

Objectives

To examine the role of mechanical ventilation since delivery room in determining severe IVH in VLBW infants in two neonatal units that follow the same strategy of respiratory management using ENCPAP.

Methods

We collected data on delivery room intubation and mechanical ventilation during the first 3 days of life in VLBW infants. Logistic regression model was constructed to test the relationship between early mechanical ventilation and the diagnosis of severe IVH after controlling for significant confounding variables, such as BW, gender, duration of mechanical ventilation, and partial pressure of CO₂ (PCO₂).

Results

Of the studied 340 VLBW, 35 infants had severe IVH; most of them received mechanical ventilation that started either in the delivery room (n = 12) or during the first (n = 10) and second (n = 3) days of life. Severe IVH was independently associated with lower BW, mechanical ventilation in the delivery room, and the cumulative duration of mechanical ventilation during the first 3 days. The adjusted odds ratio for severe IVH in infants intubated in delivery room was (OR = 2.7, CI: 1.1–6.6, P = 0.03). Severe IVH was not associated with gender, prenatal steroids, early sepsis, or patent ductus arteriosus.

Conclusions

Mechanical ventilation plays a role in predicting severe IVH. Both the time at which ventilation was initiated and the duration of ventilation are important determinants of severe IVH. Risk for severe IVH in infants who were never intubated in delivery room or during the first 3 days of life is miniscule.     

History of depressive and/or anxiety disorders as a predictor of treatment response: A post hoc analysis of a 12-week, randomized, double-blind, placebo-controlled trial of paroxetine controlled release in patients with fibromyalgia

Background

Despite of a high comorbidity of depressive and/or anxiety disorders with fibromyalgia, information on the clinical implications of this comorbidity is limited but antidepressants are commonly prescribed to treat fibromyalgia in clinical practice. We investigated whether a history of depressive and/or anxiety disorders was associated with response to paroxetine controlled release (CR) in the treatment of fibromyalgia.

Methods

One hundred sixteen (116) fibromyalgia subjects were randomized to receive paroxetine CR or placebo for 12 weeks. The primary outcome was treatment response defined as ≥ 25% reduction in the Fibromyalgia Impact Questionnaire (FIQ) score. In multivariate logistic regression, we determined if a history of depression and/or anxiety disorders was an independent predictor of response to paroxetine CR.

Results

In logistic regression, the history of depression and/or anxiety did not predict treatment response as measured by ≥ 25% reduction in Fibromyalgia Impact Questionnaire (FIQ) score (OR = 0.66, 95% CI = .29–1.49, Wald = 0.97, p = 0.32), while the drug status (paroxetine CR) was significantly associated with treatment response (OR = 2.57, CI = 1.2–5.61, Wald = 5.5, p = 0.02).

Conclusion

A significant proportion of patients with fibromyalgia had a history of anxiety and or depressive disorders. However response to treatment of fibromyalgia symptoms with paroxetine CR was not associated with a history of depressive and/or anxiety disorders. Our findings need to be confirmed in more adequately-powered and well-designed subsequent studies.     

Mismatch negativity and low frequency oscillations in schizophrenia families

Objective

Theta-alpha range oscillations have been associated with MMN in healthy controls. Our previous studies showed that theta-alpha activities are highly heritable in schizophrenia patients’ families. We aimed to test the hypothesis that theta-alpha activities may contribute to MMN in schizophrenia patients and their family members.

Methods

We compared MMN and single trial oscillations during MMN in 95 patients, 75 first-degree relatives, 87 controls, and 34 community subjects with schizophrenia spectrum personality (SSP) traits.

Results

We found that (1) MMN was reduced in patients (p < 0.001) and SSP subjects (p = 0.047) but not in relatives (p = 0.42); (2) there were augmented 1–20 Hz oscillations in patients (p = 0.02 to <0.001) during standard and deviant stimuli; (3) theta-alpha (5–12 Hz) oscillations had the strongest correlation to MMN in controls and relatives (ΔR² = 21.4–23.9%, all p < 0.001), while delta (<5 Hz) showed the strongest correlation to MMN in schizophrenia and SSP trait subjects; and, (4) MMN (h² = 0.56, p = 0.002) and theta-alpha (h² = 0.55, p = 0.004) were heritable traits.

Conclusions

Low frequency oscillations have a robust relationship with MMN and the relationship appears altered by schizophrenia; and schizophrenia patients showed augmented low frequency activities during the MMN paradigm.

Significance

The results encourage investigation of low frequency oscillations to elucidate the neurophysiological pathology underlying MMN abnormalities in schizophrenia.     

Upper extremity motor measures of Tap Test response in Normal Pressure Hydrocephalus

Objective

The Tap Test (TT) is a commonly used method for predicting shunt responsiveness in patients with Normal Pressure Hydrocephalus (NPH). The present study investigates whether measures of upper extremity motor function are useful for assessing response to spinal fluid drainage.

Methods

42 subjects undergoing evaluations for idiopathic NPH (iNPH) participated in this study. A standardized gait evaluation, a neuropsychological battery, and objective tests of upper extremity motor functions were administered. A Neurologist skilled in NPH assessment independently rated patients as TT Responders (n = 26) or Non-Responders (n = 16) based on clinical impression of change 2–4 h after 40–50 cm³ drainage of spinal fluid by lumbar puncture (LP). In the subset of subjects who underwent shunt placement, operative outcome was also evaluated.

Results

TT Responders improved significantly more than TT Non-Responders in Upper Extremity Coordination/Speed tasks (p < .001). The groups did not differ on other neuropsychological measures post-LP. A possible association was observed between pre- and post-TT changes in Upper Extremity Coordination/Speed and post-shunt improvement. Among Upper Extremity Coordination/Speed measures, Line Tracing displayed the greatest sensitivity (76%) to change post-LP.

Conclusions

Our data suggest that measures of upper extremity motor functions may be useful as measures of Tap Test response in patients with iNPH. These upper extremity motor tasks can be rapidly administered (<5 min) in clinical practice and may provide an additional dimension beyond gait and cognition for evaluating response to LP.     

Evaluation of ability for basic movement scale for children type T (ABMS-CT) for disabled children

Background

The objective of this pilot study was to test the validity and reliability of a new scale, the Ability for Basic Movement Scale for Children Type T (ABMS-CT).

Methods

Forty-nine pediatric patients with disabilities (aged 1.00–15.17 years; 29 males and 20 females) participated in this prospective study. To prove the validity and reliability of the ABMS-CT, subjects were administered the ABMS-CT by two physicians. In addition to the ABMS-CT score, data on age, diagnosis, and results of the Functional Independence Measure for Children (WeeFIM) were recorded.

Results

Spearman’s rank correlation coefficient analysis showed that the ability to perform basic movements according to the individual scores for each item on the ABMS-CT and the total scores of the ABMS-CT correlated significantly with the total scores of the motor and cognitive WeeFIM, respectively (r = 0.753–0.892, p = 0.0001). The five items on the ABMS-CT had appropriate internal consistency (Cronbach’s α = 0.966). Inter-rater reliability analysis indicated that the “oral and facial area”, “hands and fingers”, “one leg”, “both legs”, and “stairs” items on the ABMS-CT had almost perfect reliability (κ = 0.854–0.925).

Conclusion

This study provides evidence for the validity and reliability of the ABMS-CT with regard to assessment of the functional ability for complex movements in disabled pediatric patients even if they can walk independently.     

A cytokine study in children and adolescents with Tourette's disorder

Background

While immune system dysregulation has been postulated to play a role in Tourette's disorder (TD), most research has focused on the hypothesis of an autoimmune process similar to rheumatic fever. This study examined the potential role of cytokines, modulators of the immune system. We hypothesized that children with TD would have increased levels of tumor necrosis factor (TNF)-α, interleukin (IL)-12, IL-1β and IL-6, and decreased IL-2. We also explored whether comorbid obsessive compulsive disorder (OCD) had an effect on the cytokine profile of TD patients.

Method

Thirty-two children and adolescents with TD (27 males, ages 7–18 years), 17 with comorbid OCD (14 males), and 16 healthy comparison subjects (7 males, ages 9–19), were enrolled. Plasma cytokines were examined using an enzyme-linked immunosorbent assay. The Mann–Whitney and binary logistic regression tests were used to compare the groups.

Results

Only patients with comorbid OCD (TD+OCD; n = 17) had significantly elevated IL-12 plasma levels compared to controls (2.73 ± 5.12 pg/ml vs. 0.55 ± 0.88 pg/ml, rank statistic = 222.5; p < 0.04). IL-2 was significantly higher in the TD+OCD subgroup compared to the non-OCD TD subgroup (0.74 ± 0.29 pg/ml vs. 0.49 ± 0.24 pg/ml, rank statistics = 108.5; p < 0.03). There were no other significant cytokine differences between groups.

Conclusions

Findings suggest a role for IL-12 and IL-2 in TD, and that the TD+OCD subgroup may involve different neuroimmunological functions than the TD−OCD subgroup. Larger studies with medication-free patients should follow.     

Topography of maturational changes in EEG burst spectral power of the preterm infant with a normal follow-up at 2years of age

Objective

To quantify the electroencephalography (EEG) burst frequency spectrum of preterm infants by automated analysis and to describe the topography of maturational change in spectral parameters.

Methods

Eighteen preterm infants <32 weeks gestation and normal neurological follow-up at 2 years underwent weekly 4-h EEG recordings (10–20 system). The recordings (n = 77) represent a large variability in postmenstrual age (PMA, 28–36 weeks). We applied an automated burst detection algorithm and performed spectral analysis. The frequency spectrum was divided into δ1 (0.5–1 Hz), δ2 (1–4 Hz), θ (4–8 Hz), α (8–13 Hz) and β (13–30 Hz) bands. Spectral parameters were evaluated as a function of PMA by regression analysis. Results were interpolated and topographically visualised.

Results

The majority of spectral parameters show significant change with PMA. Highest correlation is found for δ and θ band. Absolute band powers decrease with increasing PMA, while relative α and β powers increase. Maturational change is largest in frontal and temporal region.

Conclusions

Topographic distribution of maturational changes in spectral parameters corresponds with studies showing ongoing gyration and postnatal white matter maturation in frontal and temporal lobes.

Significance

Computer analysis of EEG may allow objective and reproducible analysis for long-term prognosis and/or stratification of clinical treatment.     

Association of genetic polymorphisms in the type II deiodinase gene with bipolar disorder in a subset of Chinese population

Objective

Genetic factors play a critical role in the etiology of bipolar disorder (BPAD). Previous studies suggested an association between thyroid dysfunction and BPAD. We hypothesize that genetic variations in the type II deiodinase (DIO2) gene that possibly alter the bioactivity of thyroid hormones are associated with BPAD.

Method

A case–control association study was conducted in a subset of Chinese Han population. Two single nucleotide polymorphisms (SNP), open reading frame a (ORFa)-Gly3Asp (rs12885300) and Thr92Ala (rs225014) with potential functions on the activity of DIO2, were selected. The frequencies of allele, genotype and haplotype of the two SNPs were compared between the BPAD patients and the control group.

Results

Statistical significance between the BPAD patients and the control group was observed for the allele (χ² = 7.746, P = 0.005, df = 1) and genotype frequencies (χ² = 8.158, P = 0.017, df = 2) at the locus of ORFa-Gly3Asp, and for the allele (χ² = 15.838, P = 7.00e−005, df = 1) and genotype frequencies (χ² = 17.236, P = 0.0002, df = 2) at Thr92Ala. Distribution of allele 3Gly and 92Ala were significantly higher in the BPAD patients, with odds ratios of 1.489 [95% confidence interval (CI) = 1.124–1.973] and 1.616 [95% CI = 1.275–2.048], respectively. Individuals with two copies of the variant 3Gly or 92Ala were at greater risk of BPAD than individuals with one copy (dose–response manner). Haplotypes ORFa-3Asp-92Ala and ORFa-3Gly-92Ala indicated higher susceptibility for BPAD with odds ratios of 3.759 (95% CI = 2.013–7.020) and 1.292 (95% CI = 1.017–1.642), respectively, while ORFa-3Asp-92Thr probably played a protective role with an odds ratio of 0.395 (95% CI = 0.284–0.549).

Conclusion

Data generated from this study supported our hypothesis that genetic variations of the DIO2 gene were associated with BPAD and suggested further consideration on the possible involvement of these functionally active variants in the pathophysiology of BPAD.     

Age-related changes in the control of perturbation-evoked and voluntary arm movements

Objective

This study examined how handrail location predictability affects perturbation-evoked arm responses in young and older adults and whether age-related changes in perturbation-evoked arm responses are specific to mechanisms associated with reactive postural control.

Methods

Young and older adults reached for a handrail in response to a support surface translation (perturbation-evoked) or to a visual cue (voluntary). For both movement tasks, the handrail location was made predictable or unpredictable to the participant. Electromyographic (EMG) activity and kinematics of the reaching arm were recorded to quantify the arm response.

Results

Posterior deltoid EMG activity during perturbation-evoked and voluntary movements were delayed by 15–74 ms (p < 0.001) and 16% smaller (p = 0.024) when the handrail was in an unpredictable compared to a predictable location. While ageing resulted in a 12–16 ms delayed initiation of EMG activity during perturbation-evoked reaching (p = 0.003), the effects of handrail predictability and movement task did not interact with age.

Conclusions

Age-related differences in perturbation-evoked arm responses are independent of both handrail location predictability and movement task.

Significance

Age-related differences in perturbation-evoked arm responses cannot be solely attributed to declines in reactive postural control. Rather, ageing leads to a deterioration of neural mechanisms common to both perturbation-evoked and voluntary arm movements.     

Interferon, azathioprine and corticosteroids in multiple sclerosis: 6-year follow-up of the ASA cohort

Objective

To evaluate long-term effects of 2-year treatment with interferon beta combined with low-dose azathioprine and prednisone in multiple sclerosis.

Methods

In the original 2-year ASA study, 181 patients with early relapsing–remitting multiple sclerosis were randomised into 3 treatment arms: those treated with interferon beta (n = 60), with interferon beta and low-dose azathioprine (n = 58), and interferon beta, azathioprine and low-dose prednisone (n = 63). Of these, 172 were included in this 4-year non-study extension. Three monthly clinical controls and annual MRI scans were carried out. The primary endpoint was annual relapse activity. The secondary endpoints were disability and quantitative MRI parameters.

Results

Nine patients were lost to follow-up and 172 were included in the analyses. None of relapse activity, disability accumulation or MRI parameters differed significantly between the groups over 6 years. Only 5.5% and 0.6% of patients were free from disease activity at year 2 and year 6 of the treatment initiation.

Conclusion

The tested combined therapeutic regimen does not improve long-term outcomes in patients with multiple sclerosis. Furthermore, interferon is not able to completely abolish disease activity.     

Disentangling early sensory information processing deficits in schizophrenia

Objective

The disentangling of early sensory information processing deficits and examination of their relationships to demographic and clinical factors are important steps for the validation of potential biomarkers and/or endophenotypes of schizophrenia. The aims of the present study were to characterize commonly used sensory event-related potential deficits, to determine whether they are (1) distinct from one another and (2) independently associated with important clinical characteristics.

Methods

MMN, P3a and RON event-related potentials (ERP) were recorded from schizophrenia patients (SZ; n = 429) and nonpsychiatric comparison subjects (NCS; n = 286). Subgroup analyses on demographic and clinical variables were performed.

Results

Schizophrenia patients exhibited robust ERP deficits at frontocentral electrodes (MMN: d = 1.10; P3a: d = 0.87; RON: d = 0.77), consistent with previous studies. Each ERP component uniquely accounted for variance in amplitude and schizophrenia deficits. Amplitude reductions occurred with increasing age in both NCS and SZ patients. A small subset of patients prescribed combinations of 1st and 2nd generation antipsychotics exhibited significantly reduced MMN amplitude relative to other medication-defined subgroups.

Conclusions

MMN, P3a, and RON are dissociable deficits with distinct relationships to age and medication status in schizophrenia patients, potentially reflecting divergent pathophysiological processes. Reduced MMN in patients taking multiple antipsychotic medications appear to be attributable to greater severity of symptoms and functional impairments, rather than a medication effect.

Significance

Independent information processing deficits in schizophrenia patients may differentially contribute to the commonly observed deficits in neurocognitive and psychosocial functioning.     

Manganese superoxide dismutase gene Ala-9Val polymorphism might be related to the severity of abnormal involuntary movements in Korean schizophrenic patients

Objective

This study examined whether the manganese superoxide dismutase (MnSOD) gene Ala–9Val single-nucleotide polymorphism (SNP) is associated with neuroleptic-induced tardive dyskinesia (TD) and the severity of the abnormal involuntary movements in Korean schizophrenic patients.

Method

We investigated whether the MnSOD gene Ala–9Val SNP is associated with TD in Korean schizophrenic patients with (n = 83) and without (n = 126) TD who were matched for exposure to antipsychotics and other relevant variables.

Results

Logistic regression analysis revealed that being older (p = 0.026) was a risk factor for TD, but that there was no significant association between MnSOD gene and TD. Abnormal involuntary movements were more severe in carriers of the Ala allele than in noncarriers (p = 0.044).

Conclusion

These findings do not support that the MnSOD gene Ala–9Val SNP is associated with TD in Korean schizophrenic patients. However, this polymorphism might be related to the severity of abnormal involuntary movements in this population.     

The incidence of pulmonary embolism (PE) after spinal fusions

Background

Pulmonary embolism (PE) is a rare but serious event that may occur after spinal surgery.

Objective

To correlate PE incidence after spinal arthrodesis with surgical approach, region of spine operated, and primary spinal pathology. To identify PE incidence trends in this population.

Methods

The Nationwide Inpatient Sample was queried using ICD-9 codes (81.01–81.08) for spinal fusion procedures over a 21-year period (1988–2008). Other data points included PE occurrence, surgical approach, spinal region, surgical indication, and mortality. Multivariate and relational analyses were performed.

Results

4,505,556 patients were identified and 9530 had PE (incidence = 0.2%). PE patients had higher odds of combined A/P surgical approaches than posterior approaches (OR = 1.97; 95% CI = 1.66–2.33), and PE incidence was higher in thoracic versus cervical or lumbar fusions (OR = 2.54; 95% CI = 2.14–3.02). PE was more likely with vertebral fracture (OR = 1.85; 95% CI = 1.53–2.23) and SCI with vertebral fracture (OR = 4.59; 95% CI = 3.72–5.70) than without trauma. Between 1988 and 2008, the PE incidence remained stable for patients with intervertebral disk degeneration and scoliosis, but increased for patients with vertebral fracture, and SCI with vertebral fracture. There was greater inpatient mortality with occurrence of a PE (OR = 12.92; 95% CI = 10.55–14.41).

Conclusion

Although the incidence of PE in spinal arthrodesis patients is only 0.2%, there is a higher incidence after combined A/P approaches, thoracic procedures, and trauma surgical procedures. Despite the overall PE incidence remaining stable since 1988, incidence steadily increased among trauma patients. Further research is needed to explain these trends, given the context of changing patient populations and improving surgical techniques and prophylaxis measures. Greater caution and prophylaxis among trauma patients may be warranted.     

A comparison of two different continuous theta burst stimulation paradigms applied to the human primary motor cortex

Objective

The application of repetitive transcranial magnetic stimulation (rTMS) in bursts at theta frequencies (TBS) may produce lasting neuroplastic changes in the human cortex. However, there exists high variability in subjects’ responses, possibly due to non-optimal stimulation characteristics. Here we compare the efficacy of two variations of continuous TBS (cTBS) for producing neuroplastic change in the human primary motor cortex (M1).

Methods

The two cTBS paradigms were: (1) standard cTBS (cTBS_std) (three stimuli at 50 Hz, repeated at 5 Hz), and (2) modified cTBS (cTBS_mod) (three stimuli at 30 Hz, repeated at 6 Hz with intensity). Motor evoked potentials (MEPs) were recorded from the right first dorsal interosseous muscle before, as well as at 0, 5, 10, 20 and 30 min following each paradigm.

Results

Both cTBS_std (P = 0.05) and cTBS_mod (P < 0.0001) induced a suppression of MEP amplitudes. However, MEP suppression following cTBS_mod was greater (ANOVA_RM; P = 0.02). Experiments using magnetic brainstem stimulation provided evidence that cTBS_mod induced MEP suppression through cortical mechanisms.

Conclusions

The neuroplastic response of the human M1 to cTBS is highly dependent on the stimulation parameters employed.

Significance

These findings may have significant implications for the clinical application of cTBS paradigms.