An Australian experience using Tc-PSMA SPECT/CT in the primary diagnosis of prostate cancer and for staging at biochemical recurrence after local therapy.

BACKGROUND: Technetium 99 prostate-specific membrane antigen (Tc-PSMA) single-photon emission computed tomography/computed tomography (SPECT/CT) has the potential to provide greater accessibility globally than gallium 68 (Ga)-PSMA positron emission tomography (PET)/CT but has not been studied as extensively in primary diagnosis, staging, or relapse of prostate cancer (PC). We instituted a novel SPECT/CT reconstruction algorithm using Tc-PSMA and established a database to prospectively accumulate data on all patients referred with PC. This study extracts data on all patients referred over a 3.5-year period with the primary aim of comparing the diagnostic accuracy of Tc-PSMA and multiparametric magnetic resonance imaging (mpMRI) in the primary diagnosis of PC. The secondary aim was to assess the sensitivity of Tc-PSMA in detecting disease with relapse after either radical prostatectomy or primary radiotherapy. METHODS: A total of 425 men referred for primary staging (PS) of PC and 172 men referred with biochemical relapse (BCR) were evaluated. We evaluated diagnostic accuracy and correlations between Tc-PSMA SPECT/CT, magnetic resonance imaging (MRI), prostate biopsy, prostate-specific antigen (PSA), and age in the PS group and positivity rates at different PSA levels in the BCR group. RESULTS: Taking the biopsy's grade according to the International Society of Urological Pathology protocol as a reference, the sensitivity (true positive rate), specificity (true negative rate), accuracy (positive and negative predictive value), and precision (positive predictive value) for Tc-PSMA in the PS group were 99.7%, 83.3%, 99.4%, and 99.7%, respectively. Comparison rates for MRI in this group were 96.4%, 71.4%, 95.7%, and 99.1%. We found moderate correlations between Tc-PSMA uptake in the prostate and biopsy grade, the presence of metastases, and PSA. In BCR, the Tc-PSMA positive rates were 38.9%, 53.2%, 62.5%, and 84.6% at PSA levels of <0.2, 0.2 to <0.5, 0.5 to <1.0, and > 1.0 ng/mL respectively. CONCLUSIONS: We have shown that Tc-PSMA SPECT/CT using an enhanced reconstruction algorithm has a diagnostic performance similar to Ga-PSMA PET/CT and mpMRI in an everyday clinical setting. It may have some advantages in cost, sensitivity for primary lesion detection, and the ability for intraoperative localization of lymph nodes.

Monitoring sleep stages with a soft electrode array: Comparison against vPSG and home-based detection of REM sleep without atonia.

Sleep disorders are symptomatic hallmarks of a variety of medical conditions. Accurately identifying the specific stage in which these disorders occur is particularly important for the correct diagnosis of non-rapid eye movement and rapid eye movement parasomnias. In-lab polysomnography suffers from limited availability and does not reflect habitual sleep conditions, which is especially important in older adults and those with neurodegenerative diseases. We aimed to explore the feasibility and validity of a new wearable system for accurately measuring sleep at home. The system core technology is soft, printed dry electrode arrays and a miniature data acquisition unit with a cloud-based data storage for offline analysis. The positions of the electrodes allow manual scoring following the American Association of Sleep Medicine guidelines. Fifty participants (21 healthy subjects, mean age 56.6 ± 8.4 years; and 29 patients with Parkinson's disease, 65.4 ± 7.6 years) underwent a polysomnography evaluation with parallel recording with the wearable system. Total agreement between the two systems reached Cohen's kappa (k) of 0.688 with agreement in each stage of: wake k = 0.701; N1 = 0.224; N2 = 0.584; N3 = 0.410; and rapid eye movement = 0.723. Moreover, the system reliably detected rapid eye movement sleep without atonia with a sensitivity of 85.7%. Additionally, a comparison between sleep as measured in the sleep lab with data collected from a night at home showed significantly lower wake after sleep onset at home. The results demonstrate that the system is valid, accurate and allows for the exploration of sleep at home. This new system offers an opportunity to help detect sleep disorders on a larger scale than possible today, fostering better care.

Nocturnal visual hallucinations in patients with disorders of arousal: a novel behavioral and EEG pattern.

AIM: To investigate clinical and video-polysomnography (VPSG) findings of hallucinatory experiences in patients suffering from disorders of arousal (DOA) in the absence of other pathologies. METHODS: The authors retrospectively reviewed the records of 370 adults with DOA. Thirty (8.1%) patients concomitantly reported complex nocturnal visual hallucinations. VPSG recordings were scrutinized, and motor behavioral and electroencephalogram (EEG) patterns were classified according to previous descriptions of DOA. RESULTS: Thirty DOA patients reported seeing images of objects, people, and animals; either distorted, static, or mobile. The images disappeared with increased illumination in 80% of patients, and 23.3% reported preceding dream imagery. In addition to the classical DOA patterns on VPSG, a distinct pattern of behavioral and EEG manifestation associated with complex hallucinatory episodes was identified in 16 (53.3%) DOA patients. This consisted of low-voltage mixed-frequency EEG activity before eye opening that persisted while patients were observed staring or visually tracking before the onset of motor behavior. CONCLUSION: A novel, distinct behavioral and EEG pattern in patients with DOA and history of reported complex nocturnal visual hallucinations was identified. This may represent a unique phenotype of dissociation between sleep states that merits further investigation.

Cyclic alternating pattern in obstructive sleep apnea: A preliminary study.

Obstructive sleep apnea is linked to cardiovascular disease, metabolic disorders and dementia. The precise nature of the association between respiratory events in obstructive sleep apnea, cortical or subcortical arousals, and cognitive, autonomic and oxidative stress consequences remains incompletely elucidated. Previous studies have aimed to understand the relationship between obstructive sleep apnea and arousal patterns, as defined by the cyclic alternating pattern, but results have been inconsistent, in part likely due to the presence of associated comorbidities. To better define this relationship, we analysed cyclic alternating patterns in patients with obstructive sleep apnea without any additional comorbidities. We identified 18 adult male, non-obese subjects with obstructive sleep apnea and no other comorbidities or medication history, who underwent whole-night electroencephalography and polysomnography. Cyclic alternating pattern analysis was performed and verified by certified somnologists. Pairwise linear regression analysis demonstrated an inverse relationship between obstructive sleep apnea severity and cyclic alternating pattern subtype A1, and a direct correlation with cyclic alternating pattern subtype A3. Cyclic alternating pattern subtypes A1 prevail in milder obstructive sleep apnea phenotype, whilst cyclic alternating pattern subtypes A2 and A3 overcome among moderate-to-severe obstructive sleep apnea patients. The milder obstructive sleep apnea group also presented higher sleep efficiency, and increased percentages of non-rapid eye movement stage 3 and rapid eye movement sleep, as well as longer cyclic alternating pattern sequences in N3, while severe obstructive sleep apnea patients spent more time in lighter sleep stages. These results imply/suggest a balance between cyclic alternating pattern's adaptive and maladaptive arousal processes in obstructive sleep apnea of differing severities. In milder obstructive sleep apnea (apnea-hypopnea index < 20), sleep continuity may be reinforced by cyclic alternating pattern subtype A1, whereas in more severe obstructive sleep apnea, decompensation of these sleep-stabilizing mechanisms may occur and more intrusive cyclic alternating pattern fluctuations disrupt sleep circuitry.

Video polysomnographic findings in non-rapid eye movement parasomnia.

Although video polysomnography (vPSG) is not routinely recommended for the evaluation of typical cases of non-rapid eye movement (NREM) parasomnias, it can aid diagnosis of unusual cases, other sleep disorders and complicated cases with REM behaviour disorder (RBD), and in differentiating parasomnias from epilepsy. In this study, we aimed to assess vPSG findings in consecutive patients with a clinical diagnosis of NREM-parasomnia covering the whole phenotypic spectrum. Five hundred and twelve patients with a final diagnosis of NREM parasomnia who had undergone vPSG were retrospectively identified. vPSGs were analysed for features of NREM parasomnia and for the presence of other sleep disorders. Two hundred and six (40.0%) patients were clinically diagnosed with sleepwalking, 72 (14.1%) with sleep terrors, 39 (7.6%) with confusional arousals, 15 (2.9%) with sexsomnia, seven (1.4%) with sleep-related eating disorder, 122 (23.8%) with mixed phenotype, and 51 (10.0%) with parasomnia overlap disorder (POD). The vPSG supported the diagnosis of NREM parasomnia in 64.4% of the patients and of POD in 98%. In 28.9% of the patients, obstructive sleep apnea (OSA) or/and periodic limb movements during sleep (PLMS) were identified, most commonly in older, male, sleepy and obese patients. vPSG has a high diagnostic yield in patients with NREM parasomnia and should be routinely performed when there is diagnostic doubt, or in patients where there is a suspicion of OSA and PLMS.

Dreaming Characteristics in Non-Rapid Eye Movement Parasomnia and Idiopathic Rapid Eye Movement Sleep Behaviour Disorder: Similarities and Differences.

Background: Speech graph analysis (SGA) of dreams has recently shown promise as an objective and language-invariant diagnostic tool that can aid neuropsychiatric diagnosis. Whilst the notion that dreaming mentations reflect distinct physiologic processes is not new, such studies in patients with sleep disorders remain exceptionally scarce. Here, using SGA and other dream content analyses, we set to investigate structural and thematic differences in morning dream recalls of patients diagnosed with Non-Rapid Eye Movement Parasomnia (NREMP) and Idiopathic REM Sleep Behavior Disorder (iRBD). Methods: A retrospective cross-sectional study of morning dream recalls of iRBD and NREMP patients was undertaken. Traditional dream content analyses, such as Orlinsky and Hall and Van de Castle analyses, were initially conducted. Subsequently, SGA was performed in order to objectively quantify structural speech differences between the dream recalls of the two patient groups. Results: Comparable rate of morning recall of dreams in the sleep laboratory was recorded; 25% of iRBD and 18.35% of NREMP patients. Aggression in dreams was recorded by 28.57% iRBD versus 20.00% in NREMP group. iRBD patients were more likely to recall dreams (iRBD vs NREMP; P = 0.007), but they also had more white dreams, ie having a feeling of having dreamt, but with no memory of it. Visual and quantitative graph speech analyses of iRBD dreams suggested stable sequential structure, reflecting the linearity of the chronological narrative. Conversely, NREMP dream reports displayed more recursive, less stable systems, with significantly higher scores of graph connectivity measures. Conclusion: The findings of our exploratory study suggest that iRBD and NREMP patients may not only differ on what is recalled in their dreams but also, perhaps more strikingly, on how dreams are recalled. It is hoped that future SGA-led dream investigations of larger groups of patients will help discern distinct mechanistic underpinnings and any associated clinical implications.

Restricted truncal sagittal movements of rapid eye movement behaviour disorder.

Unlike sleep-walkers, patients with rapid-eye-movement-behaviour disorder (RBD) rarely leave the bed during the re-enactment of their dreams. RBD movements may be independent of spatial co-ordinates of the 'outside-world', and instead rely on (allocentric) brain-generated virtual space-maps, as evident by patients' limited truncal/axial movements. To confirm this, a semiology analysis of video-polysomnography records of 38 RBD patients was undertaken and paradoxically restricted truncal/thoraco-lumbar movements during complex dream re-enactments demonstrated.

A Novel Group Cognitive Behavioral Therapy Approach to Adult Non-rapid Eye Movement Parasomnias.

Background: Following the success of Cognitive Behavioral Therapy (CBT) for insomnia, there has been a growing recognition that similar treatment approaches might be equally beneficial for other major sleep disorders, including non-rapid eye movement (NREM) parasomnias. We have developed a novel, group-based, CBT-program for NREM parasomnias (CBT-NREMP), with the primary aim of reducing NREM parasomnia severity with relatively few treatment sessions. Methods: We investigated the effectiveness of CBT-NREMP in 46 retrospectively-identified patients, who completed five outpatient therapy sessions. The outcomes pre- and post- CBT-NREMP treatment on clinical measures of insomnia (Insomnia Severity Index), NREM parasomnias (Paris Arousal Disorders Severity Scale) and anxiety and depression (Hospital Anxiety and Depression Scale), were retrospectively collected and analyzed. In order to investigate the temporal stability of CBT-NREMP, we also assessed a subgroup of 8 patients during the 3 to 6 months follow-up period. Results: CBT-NREMP led to a reduction in clinical measures of NREM parasomnia, insomnia, and anxiety and depression severities [pre- vs. post-CBT-NREMP scores: P (Insomnia Severity Index) = 0.000054; P (Paris Arousal Disorders Severity Scale) = 0.00032; P (Hospital Anxiety and Depression Scale) = 0.037]. Improvements in clinical measures of NREM parasomnia and insomnia severities were similarly recorded for a subgroup of eight patients at follow-up, demonstrating that patients continued to improve post CBT-NREMP. Conclusion: Our findings suggest that group CBT-NREMP intervention is a safe, effective and promising treatment for NREM parasomnia, especially when precipitating and perpetuating factors are behaviorally and psychologically driven. Future randomized controlled trials are now required to robustly confirm these findings.

Cotard parasomnia: le délire de negation that occur during the sleep-wake dissociation?

None: Unpleasant dreamlike mentation can occur during non-rapid eye movement parasomnias, leading to associated panic attacks. The mentations are rarely remembered and are likely underreported. However, they may lead to significant personal distress and, if not addressed, may contribute to poorer clinical outcomes. Cotard le délire de negation are very rare nihilistic delusions, historically described with psychotic disorders. Their association with a variety of neurologic disorders, including migraine and cluster-headache, has also been reported. Here we present three cases of Cotard parasomnia during which distinct states of consciousness defined by nihilistic ideation occurred. Patients described believing they are dead or dying, while unable to perceive or experience their bodies in whole, or in part, as their own. A source analysis of the electroencephalographic fingerprint of these mentations suggests right-hemispheric hypoactivity subsequent to confusional arousals. Mechanistically, an aberrant activation of two major intrinsic brain networks of wakefulness, the salience network and the default mode network, is argued.

Cotard's Parasomnia: Le Délire de Negation that occur during the Sleep-Wake Dissociation?

NONE: Unpleasant dreamlike mentation can occur during NREM parasomnias, leading to associated panic attacks. The mentations are rarely remembered, and are likely underreported. However, they may lead to significant personal distress, and if not addressed, may contribute to poorer clinical outcomes. Cotard's 'Le Délire de Negation', are very rare nihilistic delusions, historically described with psychotic disorders. Their association with variety of neurologic disorders, including migraine and cluster-headache, has also been reported. Here we present three cases of Cotard's parasomnia during which distinct states of consciousness defined by nihilistic ideation are reported. Patients described believing to be dead or dying, whilst unable to perceive or experience their bodies in whole, or in part, as their own. The source analysis of electroencephalographic fingerprint of these mentations suggests right hemispheric hypoactivity subsequent to confusional arousals. Mechanistically, an aberrant activation of two major intrinsic brain networks of wakefulness, the salience and the default-mode-network is argued.

The clinical value of xSPECT/CT Bone versus SPECT/CT. A prospective comparison of 200 scans.

PURPOSE: To prospectively evaluate the clinical utility of xSPECT/CT Bone, a new reconstruction algorithm for single photon emission tomography (SPECT), and compare it with standard SPECT/CT reconstruction. METHODS: Sequential reporting of SPECT/CT followed by xSPECT/CT images in 200 sequential cases commencing August 2015. Differences between the initial SPECT/CT and the final report (after xSPECT/CT reconstruction) were documented and analysed. 12-18 months after the initial study follow-up, clinical data was sought from a subset of cases in which xSPECT/CT changed the primary diagnosis and imaging correlation undertaken in all patients who subsequently had MRI or CT scans of the same region. RESULTS: A majority of the 200 cases were related to assessment of musculoskeletal complaints. The final (scan) diagnosis was changed after reviewing the xSPECT/CT images in 40 (20%) of cases. The reporting physician (Iain Duncan) assessed that the xSPECT/CT had provided more diagnostic information in 71% of cases. A total of 470 additional lesions were found, equivalent to 2.4 lesions per case. In 33 cases of imaging follow-up there was a high degree of correlation with bone scan findings and xSPECT correlated better than SPECT in regard to detailed findings. In only 15/40 cases of diagnostic change could the outcome be verified and in 12/15 the xSPECT/CT revised diagnosis was confirmed. CONCLUSIONS: In this observational evaluation xSPECT/CT Bone reconstruction offers identifiable imaging improvements over standard SPECT/CT reconstruction algorithms. xSPECT/CT Bone provides an improvement in diagnostic confidence and identifies a greater number of lesions.

Catathrenia, a REM predominant disorder of arousal?

OBJECTIVES: Catathrenia is an uncommon and poorly understood disorder, characterized by groaning during sleep occurring in tandem with prolonged expiration. Its classification, pathogenesis, and clinical relevance remain debated, substantially due to the limited number of cases reported to date. We report a series of consecutive cases of catathrenia, their clinical and polysomnographic characteristics, and their subsequent management. METHODS: Consecutive patients with catathrenia who had undergone full polysomnography in our institution over a 5.5-year period were included. Catathrenia events (CEs) were examined in clusters, which formulated catathrenia periods (CPs). The relationships between CPs, sleep stage distribution, electroencephalogram (EEG) arousals, and other sleep parameters were assessed, along with the clinical presentation and management of catathrenic patients. RESULTS: A total of 427 CPs were identified in 38 patients, 81% arising from rapid eye movement (REM) sleep. EEG arousals preceded or coincided with the onset of 84% of CPs, which were of longer duration than those not associated with an arousal (57.3 ± 56.8 vs. 32.2 ± 29.4 s, p < 0.001). Each CE had a characteristic airflow signal, with inspiration preceding a protracted expiration and a brief more rapid exhalation, followed by deep inspiration. Although the majority of patients were referred on the basis of bed partner complaints, 44.7% complained of daytime sleepiness. Continuous positive airway pressure therapy and sleep-consolidating pharmacotherapy led to subjective improvement, but were limited by poor long-term adherence. CONCLUSIONS: In the largest series of catathrenia patients reported to date, we found that this rare disorder is characterized by a distinct breathing pattern and arises predominantly from REM sleep, with arousals almost uniformly preceding or coinciding with the onset of CPs.

The utility of respiratory inductance plethysmography in REM sleep scoring during multiple sleep latency testing.

Rapid eye movement sleep (REM) presents with a characteristic erratic breathing pattern. We investigated the feasibility of using respiration, derived from respiratory inductance plethysmography (RIP), in conjunction with chin electromyography, electrocardiography and pulse oximetry to facilitate the identification of REM sleep (RespREM) during nocturnal polysomnography (NPSG) and Multiple Sleep Latency Testing (MSLT). The Cohen's weighted kappa for the presence of REM and its duration in 20 consecutive NPSGs, using RespREM and compared to the current guidelines, ranged between 0.74-0.93 and 0.68-0.73 respectively for 5 scorers. The respective intraclass correlation coefficients were above 0.89. In 97.7% of the Sleep-Onset-REM-Periods (SOREMPs) during 41 consecutive MSLTs with preserved RIP, the RespREM was present and in 46.6% it coincided with the REM onset, while in the majority of the remainder RespREM preceded conventional REM onset. The erratic breathing pattern during REM, derived from RIP, is present and easily recognisable during SOREMPs in the MSLTs and may serve as a useful adjunctive measurement in identifying REM sleep.