Sarcoplasmic MxA expression A valuable marker of dermatomyositis

ABSTRACT

Objective: To evaluate the diagnostic value of myxovirus resistance A (MxA) expression in the cytoplasm of myofibers in the diagnosis of dermatomyositis (DM).

Methods: We assessed the sensitivity and specificity of the sarcoplasmic expression of MxA in muscles with DM by immunohistochemistry in consecutive cases of DM (n = 34) and other idiopathic inflammatory myopathies (n = 120: 8 with polymyositis, 16 with anti–tRNA-synthetase antibody–associated myositis, 46 with immune-mediated necrotizing myopathy, and 50 with inclusion body myositis) and compared them with conventional pathologic hallmarks of DM, including perifascicular atrophy (PFA) and membrane attack complex (MAC) deposition on endomysial capillaries.

Results: The sensitivity and specificity of sarcoplasmic MxA expression were 71% and 98%, respectively. While the specificity was almost comparable to that of PFA and capillary MAC deposition, the sensitivity was higher, with PFA showing 47% sensitivity and 98% specificity and capillary MAC deposition showing 35% sensitivity and 93% specificity. Of note, in patients with DM with typical skin rash but no PFA, 44% of the samples showed sarcoplasmic MxA expression, which was higher than the 17% sensitivity of capillary MAC deposition in the population.

Conclusions: Sarcoplasmic MxA expression detected by immunohistochemistry is a more sensitive marker of DM than the conventional hallmarks, indicating its practical utility in the diagnosis of DM. It may well be included in the routine immunohistochemistry panel for myositis.

Classification of evidence: This study provides Class II evidence that immunohistochemistry-detected sarcoplasmic MxA expression accurately identifies patients with dermatomyositis.

Neurology 2016

Sleep characteristics and cognitive impairment in the general population The HypnoLaus study

ABSTRACT

Objective: To assess the association between sleep structure and cognitive impairment in the general population.

Methods: Data stemmed from 580 participants aged >65 years of the population-based CoLaus/PsyCoLaus study (Lausanne, Switzerland) who underwent complete sleep evaluation (HypnoLaus). Evaluations included demographic characteristics, personal and treatment history, sleep complaints and habits (using validated questionnaires), and a complete polysomnography at home. Cognitive function was evaluated using a comprehensive neuropsychological test battery and a questionnaire on the participant's everyday activities. Participants with cognitive impairment (global Clinical Dementia Rating [CDR] scale score > 0) were compared with participants with no cognitive impairment (global CDR score = 0).

Results: The 291 participants with a CDR score > 0 (72.5 ± 4.6 years), compared to the 289 controls with CDR = 0 (72.1 ± 4.6 years), had significantly more light (stage N1) and less deep (stage N3) and REM sleep, as well as lower sleep efficiency, higher intrasleep wake, and higher sleepiness scores (all p < 0.05). Sleep-disordered breathing was more severe in participants with cognitive impairment with an apnea/hypopnea index (AHI) of 18.0 (7.8–35.5)/h (p50 [p25–p75]) (vs 12.9 [7.2–24.5]/h, p < 0.001), and higher oxygen desaturation index (ODI). In the multivariate analysis after adjustments for confounding variables, the AHI and the ODI ≥4% and ≥6% were independently associated with cognitive impairment.

Conclusions: Participants aged >65 years with cognitive impairment have higher sleepiness scores and a more disrupted sleep. This seems to be related to the occurrence of sleep-disordered breathing and the associated intermittent hypoxia.

Neurology 2016

• During this season of giving, let us take time to slow down and enjoy the simple things. May this wonderful time of the year touch your heart in a special way. Wishing you much happiness today and throughout the New Year.

Ictal asystole: A systematic review

Objective

To comprehensively analyze ictal asystole (IA) on a large number of subjects.

Methods

We performed a systematic review of case report studies of patients diagnosed with IA (1983–2016). Each included case was characterized with respect to patient history, IA seizure characteristics, diagnostic workup, and therapy. In addition, comparative analyses were also carried out: two alignments were developed based on the delay between epilepsy onset and IA onset (“new-onset” if <1 year, “late-onset” if ≥1 year) and asystole duration (asystole was “very prolonged” if lasted >30 s).

Results

One hundred fifty-seven cases were included. All patients had focal epilepsy. In 7% of cases IA developed during a secondary generalized tonic–clonic seizure. Both the seizure-onset zone and the focal seizure activity at asystole beginning were usually temporal (p < 0.001 and p = 0.001, respectively) and were lateralized to the left hemisphere in 62% (p = 0.005 and p = 0.05, respectively). Asystole duration was 18 ± 14 s (mean±SD) (range 3–96 s); 73% of patients had late-onset, 27% had new-onset IA. Compared to late-onset IA, new-onset IA was associated with female gender (p = 0.023), preexisting heart condition (p = 0.014), focal seizure activity at asystole beginning (p = 0.012), normal neuroimaging (p = 0.013), normal interictal EEG (p < 0.001), auditory aura (p = 0.012), and drug-responsive epilepsy (p < 0.001). “Very prolonged” asystole was associated with secondary generalized tonic–clonic seizures (p = 0.003) and tended to occur in extratemporal lobe seizures (p = 0.074). No IA-related death was reported.

Significance

Characteristics considered to be typical of IA (focal, left temporal seizures appearing on grounds of a long-lasting, intractable epilepsy) seem only partially legitimate. We suggest that in new-onset IA, female gender and a preexisting heart condition could serve as predispositions in an otherwise benign epilepsy. We speculate that in late-onset IA, male-predominant changes in neuronal networks in chronic, intractable epilepsy and an accompanying autonomic dysregulation serve as facilitating factors.

Epilepsia 2016

Distribution and characteristics of transactive response DNA binding protein 43 kDa pathology in progressive supranuclear palsy

ABSTRACT

Background

This study aimed to determine the frequency of transactive response DNA binding protein 43 kDa pathology in PSP, the clinical features of patients with this pathology, and genetic risk factors for it.

Methods

Hippocampal sections were screened with immunohistochemistry for transactive response DNA binding protein 43 kDa in 945 PSP cases. A subset of 261 cases that were negative in hippocampus was screened in the amygdala. The density and disruption of this pathology, as well as regional tau burden, and clinical and genetic characteristics were analyzed.

Results

We observed transactive response DNA binding protein 43 kDa pathology in 47 cases in the hippocampus and an additional 9 cases that only affected the amygdala. Hippocampal sclerosis was the strongest risk factor, followed by Alzheimer's disease pathology, argyrophilic grain disease, and older age at death. Five stages of transactive response DNA binding protein 43 kDa pathology were identified in PSP: Stage A had pathology only in the amygdala (16%); stage I had pathology confined to the hippocampus and entorhinal cortex (9%); stage II included both regions of stage A and I (38%); stage III spread further to medial occipitotemporal gyrus (20%); and stage IV had pathology in the dorsolateral frontal lobe (18%). Anatomical areas vulnerable to PSP pathology had varying degrees of this pathology in stage II and later. PSP with transactive response DNA binding protein 43 kDa pathology were older at disease onset and had lower median MMSE scores; however, the latter was driven by concurrent pathologies.

Conclusions

Distribution and clinical characteristics of transactive response DNA binding protein 43 kDa pathology in PSP were influenced by concurrent pathologies. This is the first study to observe that PSP-vulnerable regions are also susceptible to this non-tau pathology. 

Movement Disorders 2016

AV-1451 tau and β-amyloid positron emission tomography imaging in dementia with Lewy bodies

Abstract

Objective

Patients with probable dementia with Lewy bodies (DLB) often have Alzheimer's disease (AD)-related pathology. Our objective was to determine the pattern of positron emission tomography (PET) tau tracer AV-1451 uptake in patients with probable DLB, compared to AD, and its relationship to β-amyloid deposition on PET.

Methods

Consecutive patients with clinically probable DLB (n = 19) from the Mayo Clinic Alzheimer's Disease Research Center underwent magnetic resonance imaging, AV-1451, and Pittsburgh compound-B (PiB) PET examinations. Age- and sex-matched groups of AD dementia (n = 19) patients and clinically normal controls (n = 95) from an epidemiological cohort served as a comparison groups. Atlas- and voxel-based analyses were performed.

Results

The AD dementia group had significantly higher AV-1451 uptake than the probable DLB group, and medial temporal uptake completely distinguished AD dementia from probable DLB. Patients with probable DLB had greater AV-1451 uptake in the posterior temporoparietal and occipital cortex compared to clinically normal controls, and in probable DLB, the uptake in these regions correlated with global cortical PiB uptake (Spearman rho = 0.63; p = 0.006).

Interpretation

Medial temporal lobe AV-1451 uptake distinguishes AD dementia from probable DLB, which may be useful for differential diagnosis. Elevated posterior temporoparietal and occipital AV-1451 uptake in probable DLB and its association with global cortical PiB uptake suggest an atypical pattern of tau deposition in DLB. 

Ann Neurol 2016

Association of Periodic and Rhythmic Electroencephalographic Patterns With Seizures in Critically Ill Patients

Abstract

Importance  Periodic and rhythmic electroencephalographic patterns have been associated with risk of seizures in critically ill patients. However, specific features that confer higher seizure risk remain unclear.

Objective  To analyze the association of distinct characteristics of periodic and rhythmic patterns with seizures.

Design, Setting, and Participants  We reviewed electroencephalographic recordings from 4772 critically ill adults in 3 academic medical centers from February 2013 to September 2015 and performed a multivariate analysis to determine features associated with seizures.

Interventions  Continuous electroencephalography.

Main Outcomes and Measures  Association of periodic and rhythmic patterns and specific characteristics, such as pattern frequency (hertz), Plus modifier, prevalence, and stimulation-induced patterns, and the risk for seizures.

Results  Of the 4772 patients included in our study, 2868 were men and 1904 were women. Lateralized periodic discharges (LPDs) had the highest association with seizures regardless of frequency and the association was greater when the Plus modifier was present (58%; odds ratio [OR], 2.00, P < .001). Generalized periodic discharges (GPDs) and lateralized rhythmic delta activity (LRDA) were associated with seizures in a frequency-dependent manner (1.5-2 Hz: GPDs, 24%,OR, 2.31, P = .02; LRDA, 24%, OR, 1.79, P = .05; ≥ 2 Hz: GPDs, 32%, OR, 3.30, P < .001; LRDA, 40%, OR, 3.98, P < .001) as was the association with Plus (GPDs, 28%, OR, 3.57, P < .001; LRDA, 40%, P < .001). There was no difference in seizure incidence in patients with generalized rhythmic delta activity compared with no periodic or rhythmic pattern (13%, OR, 1.18, P = .26). Higher prevalence of LPDs and GPDs also conferred increased seizure risk (37% frequent vs 45% abundant/continuous, OR, 1.64, P = .03 for difference; 8% rare/occasional vs 15% frequent, OR, 2.71, P = .03, vs 23% abundant/continuous, OR, 1.95, P = .04). Patterns associated with stimulation did not show an additional risk for seizures from the underlying pattern risk (P > .10).

Conclusions and Relevance  In this study, LPDs, LRDA, and GPDs were associated with seizures while generalized rhythmic delta activity was not. Lateralized periodic discharges were associated with seizures at all frequencies with and without Plus modifier, but LRDA and GPDs were associated with seizures when the frequency was 1.5 Hz or faster or when associated with a Plus modifier. Increased pattern prevalence was associated with increased risk for seizures in LPDs and GPDs. Stimulus-induced patterns were not associated with such risk. These findings highlight the importance of detailed electroencephalographic interpretation using standardized nomenclature for seizure risk stratification and clinical decision making.

JAMA Neurology 2016