Autonomic symptoms following Zika virus infection

Purpose

To determine if autonomic symptoms are associated with previous Zika virus infection.

Methods

Case–control study including 35 patients with Zika virus infection without evidence of neurological disease and 105 controls. Symptoms of autonomic dysfunction were assessed with the composite autonomic symptom scale 31 (COMPASS-31).

Results

Patients with previous Zika virus infection had significantly higher COMPASS-31 score than controls regardless of age and sex (p = 0.007). The main drivers for the higher scores where orthostatic intolerance (p = 0.003), secretomotor (p = 0.04) and bladder symptoms (p < 0.001).

Conclusion

Zika virus infection is associated with autonomic dysfunction. The mechanisms remain to be elucidated.

     

Correlation between physical activity,aerobic fitness and body fat against autonomic function profile in children

Aim

To evaluate correlations between physical activity, VO_2PEAK and body fat versus autonomic function in children.

Methods

Children (n = 98) between 10 and 12 years underwent a maximal exercise test (VO_2PEAK) and dual-energy X-ray absorptiometry measured body fat. General physical activity, moderate to vigorous physical activity and vigorous physical activity were assessed by accelerometers. Deep breath test with E/I-ratio calculation and a head-up tilt test were performed. The sum of z-scores represented an index score for autonomic function profile and included E/I-ratio plus difference in blood pressure and heart rate between supine and tilted position. Correlation analyses were performed between physical activity parameters, body fat and VO_2PEAK versus autonomic function profile.

Results

No significant correlations were found between autonomic function profile and physical activity or body fat (p > 0.05). VO_2PEAK was correlated with autonomic function profile in boys (r = 0.30, p < 0.05), but not in girls (r = 0.04, NS). One girl and eight boys terminated head-up tilt test prematurely due to intolerance. Minutes of vigorous physical activity per day was lower in these boys compared with those (n = 48) who completed the head-up tilt test (5.1 ± 3.3 vs. 10.4 ± 6.6, p < 0.05).

Conclusion

Physical activity or body fat was not associated with autonomic function profile. VO_2PEAK correlated to autonomic function profile in boys.

     

The BRAIN test: a keyboard-tapping test to assess disability and clinical features of multiple sclerosis

Background

The BRadykinesia Akinesia INcordination (BRAIN) test is an online keyboard-tapping test previously validated as a sensitive tool for detecting signs of Parkinson’s disease.

Objectives

To determine whether the BRAIN test can measure disability in MS and identify the presence of pyramidal or cerebellar dysfunction.

Methods

Kinesia scores (KS, number of key taps in 30 s), akinesia times (AT, mean dwell time on each key) and incoordination scores (IS, variance of travelling time between keys) were calculated in 39 MS patients. These were correlated against the Expanded Disability Status Scale (EDSS) scores, pyramidal and cerebellar functional system scores and 9-hole peg test scores.

Results

EDSS correlated with KS (r = ? 0.594, p < 0.001), AT (r = 0.464, p = 0.003) and IS (r = 0.423, p = 0.007). 9-HPT scores strongly correlated with KS (r = 0.926, p < 0.001). Pyramidal scores correlated with KS (r = ? 0.517, p < 0.001). Cerebellar scores correlated with KS (r = ? 0.665, p < 0.001), AT (r = 0.567, p < 0.001) and IS (r = 0.546, p = 0.007). Receiver operating characteristic curves demonstrate that KS can distinguish between the presence or absence of pyramidal and cerebellar dysfunction with area under curve 0.840 (p < 0.001) and 0.829 (p < 0.001), respectively.

Conclusions

The BRAIN test can remotely measure disability in MS. Specific scores differ according to the presence and severity of pyramidal or extrapyramidal dysfunction. It demonstrates huge potential in monitoring disease progression in clinical trials.

     

Relationships between autonomic nerve function and gastric emptying in patients with autoimmune gastritis

Purpose

Autonomic nervous system dysfunction exists in autoimmune diseases. Symptoms of autoimmune gastritis are not specific, and some patients may present symptoms suggestive of delayed gastric emptying. This study aims to investigate whether any autonomic dysfunction exists in autoimmune gastritis patients, and if so, to clarify the relationship between the autonomic nervous dysfunction, delayed gastric emptying, and gastrointestinal symptoms.

Methods

75 patients (50 women, mean age 56.73 ± 11.77) diagnosed with autoimmune gastritis were investigated by means of autonomic nervous system and gastric emptying tests. All patients underwent a standardized scintigraphic gastric emptying study and five tests evaluating autonomic nervous system. Patients with autonomic nervous system dysfunction were then analyzed and compared by means of existence of delayed gastric emptying and gastrointestinal symptoms.

Results

62 patients had autonomic nervous system dysfunction (14 mild, 40 moderate, and 8 severe autonomic dysfunction). The mean total score of autonomic tests was 3.85 ± 2.35. Total autonomic score of patients (n = 60) with delayed gastric emptying was significantly higher than patients (n = 15) with normal gastric emptying (4.68 ± 1.7 vs. 1.53 ± 0.58, p < 0.001). Mean gastroparesis cardinal symptom index was significantly higher in patients (n = 60) with delayed gastric emptying half-time compared to patients (n = 15) with normal gastric emptying half-time (1.89 ± 1.16 vs 0.4 ± 0.3, p < 0.001).

Conclusions

Most of patients with autoimmune gastritis also have autonomic nerve dysfunction. There is a close relationship between autonomic nervous system dysfunction and delayed gastric emptying. Gastroparesis cardinal symptom index has a high sensitivity and specificity in predicting both autonomic nerve function and delay in gastric emptying.

     

Assessment of autonomic function in a cohort of patients with ANCA-associated vasculitis

Objective

To assess symptoms and objective parameters of autonomic dysfunction (AD) in patients with ANCA-associated vasculitides.

Methods

Symptoms and objective parameters of AD were assessed in patients with ANCA-associated vasculitis and in age-matched healthy controls. Autonomic symptoms were explored by COMPASS31, a validated questionnaire addressing symptoms of six autonomic domains (orthostatic, vasomotor, secretomotor, gastrointestinal, pupillomotor, and bladder dysfunction). Objective autonomic parameters consisted of expiratory/inspiratory (E/I) ratio during the deep breathing test (DBT), blood pressure response to cold pressor test (CPT), and skin conductance changes during mental arithmetic.

Results

27 patients and 27 healthy controls have been enrolled. 27 patients and 27 controls completed COMPASS31. 21 patients and 18 controls underwent objective autonomic testing. Vasculitis patients had significantly higher COMPASS31 total scores than controls (median 10.4 vs 3.0; p = 0.005). In the sub-domain analysis, significant differences were seen in the vasomotor and the bladder domain (p = 0.004; p < 0.001, respectively). No correlation was found between COMPASS31 score and disease duration, number of affected organs, or Birmingham vasculitis activity score (BVAS). There was no significant difference in any of the objective autonomic parameters between patients and controls. In a subgroup analysis, no difference in objective autonomic parameters was found between patients with active disease (n = 12) and patients in remission (n = 7).

Conclusion

Patients with ANCA-associated vasculitides commonly have symptoms of autonomic dysfunction that are independent of disease duration and disease severity. However, at least in this single-centre observation, there was no evidence of impaired autonomic regulation in three autonomic function tests in vasculitis patients.

     

Pupillary autonomic dysfunction in patients with ANCA-associated vasculitis

Objective

To assess autonomic function by infrared dynamic pupillometry in patients with ANCA-vasculitis (AAV) in correlation to autonomic symptoms, disease specific clinical parameters and cardiovascular reflex tests.

Methods

Patients with AAV and healthy controls underwent pupillometry at rest and after sympathetic stimulation (cold pressor test). Three parasympathetic parameters (amplitude, relative amplitude, maximum constriction velocity) and one sympathetic parameter (late dilatation velocity) were assessed. Results were correlated with clinical parameters, symptoms of autonomic dysfunction (COMPASS31 questionnaire), heart rate variability during deep breathing test and blood pressure response to pain.

Results

23 patients and 18 age-matched controls were enrolled. Patients had a smaller amplitude (1.44 vs. 1.70 mm; p = 0.009) and a slower constriction velocity (4.15 vs. 4.71 mm/s; p = 0.028) at baseline and after sympathetic stimulation (1.47 vs. 1.81 mm, p = 0.001; 4.38 vs. 5.19 mm/s, p = 0.006, respectively). Relative amplitude was significantly smaller in patients after sympathetic stimulation (28.6 vs. 32.5%; p = 0.043), but not at baseline. There was no difference in sympathetic pupillary response between the groups. In patients, parasympathetic pupil response was correlated negatively with age and positively with parasympathetic cardiac response. After adjusting for age, no significant correlation was observed with clinical parameters. However, there was a trend towards a negative correlation with disease duration, vasculitis damage index and CRP.

Conclusion

Patients with AAV exhibit parasympathetic pupillary autonomic dysfunction. Although correlations were weak and not significant, pupillary autonomic dysfunction is rather linked to chronic damage than to active inflammation or symptoms of autonomic dysfunction.

     

Correlation between indexes of autonomic maneuvers and heart rate variability in hemodialysis patients

Purpose

The autonomic maneuvers are simple methods to evaluate autonomic balance, but the association between autonomic maneuvers and heart rate variability (HRV) in hemodialysis patients remains unknown. This study aimed to evaluate the correlation between HRV and respiratory sinus arrhythmia (RSA) and Valsalva maneuver (VM) indexes in hemodialysis patients and to compare two methods for RSA indexes acquisitions.

Methods

Forty-eight volunteers on hemodialysis (66.7 % men) were evaluated by VM, RSA, and 24 h Holter monitoring. At the VM, the Valsalva index (VI) was the variable considered. In the RSA, the ratio and difference between the RR intervals of inspiratory and expiratory phase (E:I and E–I, respectively) were considered by traditional form (average of respiratory cycles) and independent respiratory cycles (E:Iindep and E–Iindep). The HRV indexes evaluated were standard deviation of all normal RR intervals (SDNN), standard deviation of sequential 5-min RR interval means (SDANN), root mean square of the successive differences (rMSSD) and percentage of adjacent RR intervals with difference of duration greater than 50 ms (pNN50).

Results

The SDNN, SDANN showed significant correlation with all classic indexes of RSA (E:I: r = 0.62, 0.55, respectively, E–I: r = 0.64, 0.57, respectively), E:Iindep (r = 0.59, 0.54, respectively), E–Iindep (r = 0.47, 0.43, respectively) and VI (r = 0.42, 0.34, respectively). Significant correlation of rMSSD with E:I (r = 0.37), E–I (r = 0.41) and E:Iindep (r = 0.34) was also observed. There was no association of any variable with pNN50. Have been show high values for all variables of independent cycles method (p < 0.05).

Conclusion

The autonomic maneuvers, especially RSA, are useful methods to evaluate cardiac autonomic function in hemodialysis patients. The acquisition of the RSA index by independent cycles should not be used in this population.

     

Cerebral Ventricular Dimensions After Decompressive Craniectomy: A Comparison Between Bedside Sonographic Duplex Technique and Cranial Computed Tomography

Background

The objective of this study was to assess and compare ventricle diameters in patients after decompressive craniectomy by using cranial computed tomography (CCT) versus sonographic duplex technique (SDT).

Methods

A total of 102 consecutive patients after decompressive craniectomy following brain infarct, bleeding and trauma were examined by CCT and SDT. SDT was performed within 24 h after repeated postinterventional control CCT and the correlation between both methods was assessed via measurement of dimensions of all four ventricles. In addition, midline shifts and overall cerebral anatomy was evaluated.

Results

A high correlation was found between CCT and SDT in measuring the diameters of all four ventricles (right lateral r = 0.978, p < 0.001; left lateral r = 0.975, p < 0.001; third r = 0.987, p < 0.001 and fourth ventricle r = 0.954, p < 0.001). Deviations of midline structure was observed in SDT as well as in CCT (r = 0.992, p < 0.001).

Conclusion

SDT in patients after decompressive craniectomy may represent an additional bedside tool to assess the dimensions of the ventricular system, anatomical structures, e.g., subdural hygromas, hematomas, midline shifts, gyri and sulci. The measurement of the dimensions of all four ventricles by using SDT delivers accurate values and may be considered as an alternative to CCT or a trigger for CCT prior to further treatment.

     

Muscle sympathetic nerve activity in frontotemporal lobar degeneration is similar to amyotrophic lateral sclerosis

Purpose

To determine whether frontotemporal lobar degeneration (FTLD) is associated with similar cardiovascular autonomic dysfunction to that seen in amyotrophic lateral sclerosis (ALS), we compared cardiovascular parameters between ALS patients and patients with FTLD.

Methods

In ten patients with FTLD (mean age ± SD: 71.6 ± 4.6 years) and 12 patients with ALS (mean age ± SD: 71.4 ± 4.6 years), MSNA (using microneurography), heart rate (HR), and blood pressure (BP) were recorded simultaneously.

Results

MSNA was significantly higher in both groups of patients compared with the controls (p < 0.01), while there were no significant differences in MSNA between the patients with FTLD and those with ALS. During head-up tilt, changes in HR, BP, and the frequency of MSNA bursts were smaller in the patients than in controls (p < 0.05 or p < 0.01).

Conclusions

Patients with FTLD and ALS showed similar dysfunction of HR, BP, and sympathetic outflow to muscles.

     

The symptoms of autonomic dysfunction in HIV-positive Africans

Background

Human immunodeficiency virus (HIV) infection is associated with autonomic neuropathy. The resultant autonomic dysfunction impairs quality of life and can have fatal consequences. Our aim was to clearly define the symptoms of autonomic dysfunction in African HIV-positive patients and determine whether these symptoms were related with (a) autonomic reflex responses (b) the degree of immunosupression.

Methods

Thirty-one HIV-positive treatment-naïve African patients (mean CD4 cell count 269.5 ± 253.4/mm³) and 12 healthy controls completed a detailed questionnaire (Autonomic System Profile, Mayo Clinic, Rochester, MN) relating to specific symptoms of autonomic dysfunction. After completion of the questionnaire, subjects underwent a standard battery of autonomic reflex tests.

Results

The autonomic symptom score was higher in the male HIV-positive patients (26.7 ± 14.7 points) and female patients with CD4 <200/mm³ (24.7 ± 18.0) than sex-matched controls (male controls, 9.9 ± 6.8, P < 0.05; female controls, 8.8 ± 10.1; P < 0.05). Six patients had scores indicative of severe autonomic dysfunction (>43.8 points). The most common autonomic symptoms were: orthostatic intolerance, secretomotor and gastrointestinal dysfunction. There was no relationship between CD4 cell counts and autonomic symptom scores. The blood pressure response to sustained handgrip was blunted, but all other cardiovascular reflex tests were within the normal range or borderline.

Conclusion

African HIV-positive patients report symptoms of autonomic dysfunction, despite normal or borderline autonomic reflex responses.

     

Spontaneous cervical artery dissection is accompanied by a hypercoagulable state and simultaneous inflammatory condition

Background

Spontaneous cervical artery dissections (sCAD) are often preceded by infections. However, existing data about inflammatory parameters remained inconsistent. Remarkably, concurrent information about the coagulation system, whose affection seems also reasonable to cause ischaemic events, are still lacking in sCAD patients. Thus, this study explores the association between the inflammatory and coagulation system in patients with sCAD.

Methods

The parameters leukocyte and thrombocyte count, C-reactive protein, fibrinogen, D-dimer, activated partial thromboplastin time (aPTT) and prothrombin time were extracted from hospital-based medical records of patients (n = 60) with sCAD and compared with those of a control group (n = 97) from a prospective observational stroke study. Univariate analyses were added by multiple regression analyses.

Results

As compared with the control group, patients with sCAD had an increased leucocyte count (9.2 ± 3.2 vs. 7.9 ± 2.2 × 10⁹/l; p = 0.003), an increased thrombocyte count (252 ± 52 vs. 229 ± 64 × 10⁹/l; p = 0.021), a shortened aPTT 28.0 ± 3.5 vs. 29.9 ± 3.6 s; p = 0.001) and decreased D-dimer values (0.44 ± 0.29 vs. 0.76 ± 0.73 mg/l; p = 0.002). However, in multiple regression analyses adjusted for age, sex, initial stroke severity, arterial hypertension, diabetes mellitus and smoking only the shortened aPTT remained statistically significant (p = 0.045) between groups, while differences on leucocyte count (p = 0.087), thrombocyte count (p = 0.234) and D-dimer (p = 0.321) failed statistical significance.

Conclusion

We found evidence for a hypercoagulable state in patients with sCAD as indicated by a shortened aPTT, which was associated with a trend to an increased leucocyte count at the same time. Our findings first strengthen the hypothesis that inflammation critically impacts on the occurrence of sCAD, and second linked this condition with a marked affection of the coagulation system.

     

Supine hypertension in Parkinson’s disease and multiple system atrophy

Objective

Supine hypertension (SH) is a feature of cardiovascular autonomic failure that often accompanies orthostatic hypotension and may represent a negative prognostic factor in parkinsonian syndromes. Here we investigated the frequency rate as well as the clinical and tilt test correlates of SH in Parkinson’s disease (PD) and multiple system atrophy (MSA).

Methods

197 PD (33 demented) and 78 MSA (24 MSA-Cerebellar, 54 MSA-Parkinsonian) patients who had undergone a tilt test examination were retrospectively included. Clinical-demographic characteristics were collected from clinical records at the time of the tilt test examination.

Results

SH (>140 mmHg systolic, >90 mmHg diastolic) occurred in 34 % of PD patients (n = 66, mild in 71 % of patients, moderate in 27 %, severe in 2 %) and 37 % of MSA ones (n = 29, mild in 55 % of patients, moderate in 17 %, severe in 28 %). No difference was observed in SH frequency between demented versus gender-, age- and disease duration-matched non-demented PD patients, or between patients with the parkinsonian (MSA-P) versus the cerebellar (MSA-C) variant of MSA. In PD, SH was associated with presence of cardiovascular comorbidities (p = 0.002) and greater systolic (p = 0.007) and diastolic (p = 0.002) orthostatic blood pressure fall. Orthostatic hypotension (p = 0.002), and to a lesser degree, lower daily dopaminergic intake (p = 0.01) and use of anti-hypertensive medications (p = 0.04) were associated with SH in MSA.

Interpretation

One-third of PD and MSA patients suffer from mild to severe SH, independently of age, disease duration or stage. In PD, cardiovascular comorbidities significantly contribute to the development of SH, while in MSA, SH appears to reflect cardiovascular autonomic failure.

     

Sleep disorders in patients with postural tachycardia syndrome

Objective

Patients with postural tachycardia syndrome (POTS) often describe symptoms of fatigue, sleepiness, and lack of refreshing sleep. We aimed to provide further objective measures of sleep in patients with POTS.

Methods

POTS patients (n = 18) were selected based on autonomic testing and evaluation at our center. Controls (n = 16) of similar age, gender, and BMI were selected from new patients referred to the Stanford Sleep Disorders Clinic for any sleep-related complaint. All patients underwent polysomnography and completed several sleep questionnaires and a 2-week sleep diary.

Results

POTS patients and control subjects were of similar age (27 ± 10.2 vs. 29 ± 5.4 years, p = 0.92) and Body Mass Index (21 ± 3.8 vs. 24 ± 4.1, p = 0.14). The majority of subjects in both groups were females (72 % POTS vs. 81 % controls). POTS patients scored higher on subjective fatigue scales but not sleepiness scales. POTS patients scored in the normal range on the BDI and the “evening” category on the MEQ. Their sleep diaries were not different from controls. With the exception of mild OSA, slightly reduced %REM and prolonged REM latency, their PSG data were normal and no different from controls.

Conclusions

It is unlikely that the sleep-related complaints of POTS patients are the result of a primary sleep disorder unique to POTS. We propose that a combination of factors such as body fatigue, chronic pain, and other somatic symptoms common in POTS patients might be the underlying reason for sleep-related symptoms in POTS.

     

Non-invasive Monitoring of Dynamic Cerebrovascular Autoregulation Using Near Infrared Spectroscopy and the Finometer Photoplethysmograph

Background

Near infrared spectroscopy (NIRS) enables continuous monitoring of dynamic cerebrovascular autoregulation, but this methodology relies on invasive blood pressure monitoring (iABP). We evaluated the agreement between a NIRS based autoregulation index calculated from invasive blood pressure monitoring, and an entirely non-invasively derived autoregulation index from continuous non-invasive blood pressure monitoring (nABP) using the Finometer photoplethysmograph.

Methods

Autoregulation was calculated as the moving correlation coefficient between iABP and rSO₂ (iTOx) or nABP and rSO₂ (nTOx). The blood pressure range where autoregulation is optimal was also determined for invasive (iABP_OPT) and non-invasive blood pressure measurements (nABP_OPT).

Results

102 simultaneous bilateral measurements of iTOx and nTOx were performed in 19 patients (median 2 per patient, range 1–9) with different acute pathologies (sepsis, cardiac arrest, head injury, stroke). Average iTOx was 0.01 ± 0.13 and nTOx was 0.01 ± 0.11. The correlation between iTOx and nTOx was r = 0.87, p < 0.001, 95 % agreement ± 0.12, bias = 0.005. The interhemispheric asymmetry of autoregulation was similarly assessed with iTOx and nTOx (r = 0.81, p < 0.001). Correlation between iABP_OPT and nABP_OPT was r = 0.47, p = 0.003, 95 % agreement ± 32.1 mmHg, bias = 5.8 mmHg. Coherence in the low frequency spectrum between iABP and nABP was 0.86 ± 0.08 and gain was 1.32 ± 0.77.

Conclusions

The results suggest that dynamic cerebrovascular autoregulation can be continuously assessed entirely non-invasively using nTOx. This allows for autoregulation assessment using spontaneous blood pressure fluctuations in conditions where iABP is not routinely monitored. The nABP_OPT might deviate from iABP_OPT, likely because of discordance between absolute nABP and iABP readings.

     

Positive effects of fampridine on cognition,fatigue and depression in patients with multiple sclerosis over 2 years

Objective

To assess the effects of PR-fampridine on cognitive functioning, fatigue and depression in patients with multiple sclerosis (PwMS).

Methods

Thirty-two PwMS were included in this trial. Cognitive performance was assessed in an open-label and randomized double-blind, placebo-controlled study design using a comprehensive neuropsychological test battery as well as questionnaires examining depression and fatigue.

Results

We found significant improvements in cognitive measures assessing alertness (tonic alertness, p = 0.0244 and phasic alertness, p = 0.0428), psychomotor speed (p = 0.0140) as well as verbal fluency (p = 0.0002) during open-label treatment with PR-fampridine. These effects of performance were paralleled by patients’ perception of reduced fatigue (physical, p = 0.0131; cognitive, p = 0.0225; total, p = 0.0126). Fampridine-induced improvements in phasic alertness (p = 0.0010) and measures of fatigue (physical, p = 0.0014; cognitive, p = 0.0003; total, p = 0.0005) were confirmed during randomized, double-blind, placebo-controlled assessment in the second year. In addition, we found positive effects of PR-fampridine on depressive symptoms (p = 0.0049). We demonstrated persisting beneficial effects of PR-fampridine on fatigue in PwMS over a period of more than 2 years. Drug responsiveness regarding cognitive performance and fatigue was not limited to walking responders.

Conclusions

Our data demonstrate significant positive effects of treatment with PR-fampridine over 2 years on different cognitive domains as well as fatigue and depression in a cohort of PwMS. These findings imply that PR-fampridine should be considered as symptomatic treatment improving aspects of cognition, fatigue and depression in PwMS.

     

Longitudinal predictors of caregiver burden in amyotrophic lateral sclerosis: a population-based cohort of patient–caregiver dyads

Objective

Caregiver burden is a recognised consequence of caring for a patient with neurodegeneration. Amyotrophic lateral sclerosis (ALS) differs from other neurodegenerations by its rapid progression and impairment of motor, cognitive, and behavioural function, which contribute to caregiver burden. However, longitudinal factors that determine the extent of caregiver burden, and in particular the impact of psychological distress among caregivers, have not been fully established.

Methods

Patients with ALS (n = 85) and their primary caregivers (n = 85) completed three serial evaluations. Caregiver burden was measured using the Zarit Burden Interview (ZBI). Anxiety and depression were evaluated using the Hospital Anxiety and Depression Scale (HADS). The Edinburgh Cognitive-Behavioural ALS Screen (ECAS) was used to determine cognitive function in patients. The ALS Functional Rating Scale (ALSFRS-R) measured disease progression.

Results

Using the ZBI, caregivers were categorised as high or low burden. In the low burden group, anxiety scores from the HADS predicted caregiver burden (r = 0.410, F = 3.73, p = 0.033), whereas the depression sub-score from the HADS was predictive of caregiver burden in the high burden group (r = 0.501, F = 5.87, p = 0.006) for cross-sectional analyses. Longitudinally, an elevated score on the HADS at Time 1 was the largest predictor of caregiver burden across serial assessments.

Conclusion

In a patient cohort with relatively preserved cognitive function (65%), anxiety and depression at Time 1, as measured by the HADS, were the best predictors of caregiver burden at Time 3. This observation provides a mechanism by which caregiver burden can be identified by health-care professionals and a stepped care programme of intervention initiated.

     

Regional Differences in Cerebral Glucose Metabolism After Cardiac Arrest and Resuscitation in Rats Using [<Superscript>18</Superscript>F]FDG Positron Emission Tomography and Autoradiography

Background

Cardiac arrest is an important cause of morbidity and mortality. Brain injury severity and prognosis of cardiac arrest patients are related to the cerebral areas affected. To this aim, we evaluated the variability and the distribution of brain glucose metabolism after cardiac arrest and resuscitation in an adult rat model.

Methods

Ten rats underwent 8-min cardiac arrest, induced with a mixture of potassium and esmolol, and resuscitation, performed with chest compressions and epinephrine. Eight sham animals received anesthesia and experimental procedures identical to the ischemic group except cardiac arrest induction. Brain metabolism was assessed using [¹⁸F]FDG autoradiography and small animal-dedicated positron emission tomography.

Results

The absolute glucose metabolism measured with [¹⁸F]FDG autoradiography 2 h after cardiac arrest and resuscitation was lower in the frontal, parietal, occipital, and temporal cortices of cardiac arrest animals, showing, respectively, a 36% (p = 0.006), 32% (p = 0.016), 36% (p = 0.009), and 32% (p = 0.013) decrease compared to sham group. Striatum, hippocampus, thalamus, brainstem, and cerebellum showed no significant changes. Relative regional metabolism indicated a redistribution of metabolism from cortical area to brainstem and cerebellum.

Conclusions

Our data suggest that cerebral regions have different susceptibility to moderate global ischemia in terms of glucose metabolism. The neocortex showed a higher sensibility to hypoxia–ischemia than other regions. Other subcortical regions, in particular brainstem and cerebellum, showed no significant change compared to non-ischemic rats.

     

Community treatment orders and social outcomes for patients with psychosis: a 48-month follow-up study

Purpose

Community treatment orders (CTOs) are widely used internationally despite a lack of evidence supporting their effectiveness. Most effectiveness studies are relatively short (12-months or less) and focus on clinical symptoms and service data, while a little attention is given to patients’ social outcomes and broader welfare. We tested the association between the duration of CTO intervention and patients’ long-term social outcomes.

Methods

A sub-sample (n = 114) of community-based patients from the Oxford Community Treatment Order Evaluation Trial (OCTET) were interviewed 48 months after randomisation. Multivariate regression models were used to examine the association between the duration of the CTO intervention and social outcomes as measured by the social network schedule, Objective Social Outcomes Index, Euro-Qol EQ-5D-3L (EQ-5D), and Oxford Capabilities Questionnaire for Mental Health.

Results

No significant association was found between the duration of CTO intervention and social network size (IRR = 0.996, p = .63), objective social outcomes (B = ?0.003, p = .77), health-related quality of life (B = 0.001, p = .77), and capabilities (B = 0.046, p = .41). There were no between-group differences in social outcomes when outcomes were stratified by original arm of randomisation. Patients had a mean of 10.2 (SD = 5.9) contacts in their social networks, 42% of whom were relatives.

Conclusions

CTO duration was not associated with improvements in patients’ social outcomes even over the long term. This study adds to growing concerns about CTO effectiveness and the justification for their continued use.

     

Revisiting Grade 3 Diffuse Axonal Injury: Not All Brainstem Microbleeds are Prognostically Equal

Background

Recovery of functional independence is possible in patients with brainstem traumatic axonal injury (TAI), also referred to as “grade 3 diffuse axonal injury,” but acute prognostic biomarkers are lacking. We hypothesized that the extent of dorsal brainstem TAI measured by burden of traumatic microbleeds (TMBs) correlates with 1-year functional outcome more strongly than does ventral brainstem, corpus callosal, or global brain TMB burden. Further, we hypothesized that TMBs within brainstem nuclei of the ascending arousal network (AAN) correlate with 1-year outcome.

Methods

Using a prospective outcome database of patients treated for moderate-to-severe traumatic brain injury at an inpatient rehabilitation hospital, we retrospectively identified 39 patients who underwent acute gradient-recalled echo (GRE) magnetic resonance imaging (MRI). TMBs were counted on the acute GRE scans globally and in the dorsal brainstem, ventral brainstem, and corpus callosum. TMBs were also mapped onto an atlas of AAN nuclei. The primary outcome was the disability rating scale (DRS) score at 1 year post-injury. Associations between regional TMBs, AAN TMB volume, and 1-year DRS score were assessed by calculating Spearman rank correlation coefficients.

Results

Mean ± SD number of TMBs was: dorsal brainstem = 0.7 ± 1.4, ventral brainstem = 0.2 ± 0.6, corpus callosum = 1.8 ± 2.8, and global = 14.4 ± 12.5. The mean ± SD TMB volume within AAN nuclei was 6.1 ± 18.7 mm³. Increased dorsal brainstem TMBs and larger AAN TMB volume correlated with worse 1-year outcomes (R = 0.37, p = 0.02, and R = 0.36, p = 0.02, respectively). Global, callosal, and ventral brainstem TMBs did not correlate with outcomes.

Conclusions

These findings suggest that dorsal brainstem TAI, especially involving AAN nuclei, may have greater prognostic utility than the total number of lesions in the brain or brainstem.

     

The yield of non-elective inpatient video-EEG monitoring in adults

Background

Inpatient video-EEG monitoring (VEM) can contribute to the diagnosis and treatment in many of the monitored patients. Most admissions to VEM are elective and are scheduled ahead before the monitoring session.

Purpose

To retrospectively evaluate the yield of non-elective VEM sessions.

Methods

We retrospectively reviewed the VEM recordings and medical records of all the patients admitted to our one-bed VEM unit from June 2007 to June 2015. A VEM session was diagnostic when a seizure, an event or previously unreported interictal epileptiform discharges were recorded.

Results

The study group included 304 adults aged 18–92 years (mean 40.4 ± 17.4 years), 181 (59%) women. The diagnostic yield of non-elective and elective VEM session was similar (66 and 69%, respectively). In non-elective VEM, fewer patients had known epilepsy (p = 0.0001), session duration was shorter (p = 0.0001), and seizures and interictal epileptiform discharges were recorded less frequently compared to elective VEM (p = 0.005 and p = 0.0001, respectively).

Conclusion

Non-elective VEM can provide useful information in patients admitted to the neurology department with recent neurological or behavioral events. A timely and correct diagnosis in these patients can potentially reduce unnecessary use of antiepileptic drugs in patients with psychogenic nonepileptic seizures and the morbidity and mortality associated with undiagnosed seizures.