Cerebellar Superficial Siderosis in Cerebral Amyloid Angiopathy on 1.5T T2*-Weighted Imaging.

BACKGROUND: Cerebellar superficial siderosis (SS) has been recently reported to be present in about 10% of both hereditary and sporadic cerebral amyloid angiopathy (CAA) on 3T MRI using primarily susceptibility-weighted imaging. OBJECTIVES: Our aim was to assess cerebellar SS in sporadic CAA patients using 1.5T T2*-weighted MRI and to evaluate possible underlying mechanisms. METHOD: We retrospectively screened MRI scans of sporadic probable CAA patients initially presenting with intracerebral hemorrhage-, acute subarachnoid hemorrhage- or cortical SS-related symptoms between September 2009 and January 2022 registered in our stroke database. Patients with familial CAA were excluded. On 1.5T T2*-weighted MRI, cerebellar SS (including kappa statistics for interobserver agreement) was assessed together with typical CAA hemorrhagic features and with the presence of supratentorial macrobleed and cortical SS adjacent to the tentorium cerebelli (TC) and TC hemosiderosis. RESULTS: We screened 151 patients and finally included 111 CAA patients (median age 77) with cerebellar SS observed in 6 (5%) patients. Cerebellar SS presence was associated with a higher number of supratentorial macrobleeds (median n = 3 vs. n = 1, p = 0.0012), presence of supratentorial macrobleed adjacent to the TC (p = 0.002), and TC hemosiderosis (p = 0.005). CONCLUSIONS: Cerebellar SS in CAA patients can be identified on 1.5T T2*-weighted imaging. Associated MRI characteristics suggest contamination from supratentorial macrobleeds.

Unilateral subcortical extensive dilated perivascular spaces associated with superior sagittal sinus perivenous dilated spaces.

We present the MRI of a 70-year-old patient showing unilateral subcortical extensive dilated perivascular spaces with surrounding fluid-attenuated inversion recovery hyperintensities associated with the presence of small cysts and tubular hypointensities in and near the superior sagittal sinus co-locating with draining cortical veins on gadolinium-enhanced T1-weighted imaging representing probably (dilated) spaces between pial sheath and cortical vein walls. These (peri)venous superior sagittal sinus cysts seem to represent either hydrops cause (by blocking interstitial fluid flow in perivenous subpial space, via meningeal lymphatics) or consequence (where cysts might have been formed due to subpial fluid flow obstruction by unknown cause).

Brain hemorrhage on 24h-CT and functional outcome in stroke patients with cerebral amyloid angiopathy features on pre-thrombolysis MRI treated with intravenous thrombolysis: A case series.

BACKGROUND AND OBJECTIVES: In stroke patients treated with intravenous thrombolysis (IVT), presence and high number of strictly lobar cerebral microbleeds (compatible with cerebral amyloid angiopathy, CAA) seems to be associated with increased risk of hemorrhagic transformation, symptomatic hemorrhagic transformation, remote hemorrhage, and poor functional outcome. Some of these CAA patients with cerebral microbleeds also have chronic lobar intracerebral hemorrhage. Few data are available on IVT-treated CAA patients showing cortical superficial siderosis. There are no reports studying factors associated with brain hemorrhagic complication or functional outcome in IVT-treated CAA patients. We present a case series study of IVT-treated stroke patients with CAA features on pre-IVT MRI in whom we have evaluated brain hemorrhagic complications on 24 h-CT and functional outcome after IVT. MATERIAL AND METHODS: In our stroke center, IVT decision in patients with CAA MRI features is at the physician's discretion. We retrospectively screened our stroke database between January 2015 and July 2022 for pre-IVT imaging of 959 consecutive IVT-treated stroke patients without ongoing anticoagulation therapy for probable CAA MRI features defined by modified Boston criteria. After exclusion of 119 patients with missing MRI (n = 47), MRI showing motion artefacts (n = 49) or with alternative chronic brain hemorrhage cause on MRI (n = 23), 15 IVT-treated patients with probable CAA on pre-IVT MRI were identified. In these 15 patients, clinical, biological and MRI characteristics were compared between patients with vs. without post-IVT hemorrhage and between patients with poor (MRS 3-6) vs. good (MRS 0-2) functional outcome at discharge. RESULTS: Two patients showed brain hemorrhage on 24 h-CT and both died after 40 and 31 days respectively. The remaining patients had no brain hemorrhage and showed very good outcome except one. Atrial fibrillation (p = 0.029) and Fazekas scale (p = 0.029) were associated with brain hemorrhage whereas atrial fibrillation (p = 0.0022), NIHSS (p = 0.027), blood glucose level (p = 0.024), CRP (p = 0.022) and DWI ASPECT (p = 0.016) were associated with poor outcome. DISCUSSION: Consequences of IVT in CAA patients can be dramatic. Larger studies are needed to compare IVT risks and outcome between CAA and non-CAA patients, also including CAA patients with chronic intracerebral hemorrhage or cortical superficial siderosis. In addition, future studies should try to identify clinical, biological and radiological features at high risk for brain hemorrhage and poor outcome in order to assess the risk-benefit ratio for IVT in CAA. CLINICAL TRIAL REGISTRATION-URL: http://www. CLINICALTRIALS: gov. Unique identifier: NCT05565144.

Sodium Oxybate for Excessive Daytime Sleepiness and Sleep Disturbance in Parkinson Disease: A Randomized Clinical Trial.

Importance: Sleep-wake disorders are a common and debilitating nonmotor manifestation of Parkinson disease (PD), but treatment options are scarce. Objective: To determine whether nocturnal administration of sodium oxybate, a first-line treatment in narcolepsy, is effective and safe for excessive daytime sleepiness (EDS) and disturbed nighttime sleep in patients with PD. Design, Setting, and Participants: Randomized, double-blind, placebo-controlled, crossover phase 2a study carried out between January 9, 2015, and February 24, 2017. In a single-center study in the sleep laboratory at the University Hospital Zurich, Zurich, Switzerland, 18 patients with PD and EDS (Epworth Sleepiness Scale [ESS] score >10) were screened in the sleep laboratory. Five patients were excluded owing to the polysomnographic diagnosis of sleep apnea and 1 patient withdrew consent. Thus, 12 patients were randomized to a treatment sequence (sodium oxybate followed by placebo or placebo followed by sodium oxybate, ratio 1:1) and, after dropout of 1 patient owing to an unrelated adverse event during the washout period, 11 patients completed the study. Two patients developed obstructive sleep apnea during sodium oxybate treatment (1 was the dropout) and were excluded from the per-protocol analysis (n = 10) but included in the intention-to-treat analysis (n = 12). Interventions: Nocturnal sodium oxybate and placebo taken at bedtime and 2.5 to 4.0 hours later with an individually titrated dose between 3.0 and 9.0 g per night for 6 weeks with a 2- to 4-week washout period interposed. Main Outcomes and Measures: Primary outcome measure was change of objective EDS as electrophysiologically measured by mean sleep latency in the Multiple Sleep Latency Test. Secondary outcome measures included change of subjective EDS (ESS), sleep quality (Parkinson Disease Sleep Scale-2), and objective variables of nighttime sleep (polysomnography). Results: Among 12 patients in the intention-to-treat population (10 men, 2 women; mean [SD] age, 62 [11.1] years; disease duration, 8.4 [4.6] years), sodium oxybate substantially improved EDS as measured objectively (mean sleep latency, +2.9 minutes; 95% CI, 2.1 to 3.8 minutes; P = .002) and subjectively (ESS score, -4.2 points ; 95% CI, -5.3 to -3.0 points; P = .001). Thereby, 8 (67%) patients exhibited an electrophysiologically defined positive treatment response. Moreover, sodium oxybate significantly enhanced subjective sleep quality and objectively measured slow-wave sleep duration (+72.7 minutes; 95% CI, 55.7 to 89.7 minutes; P < .001). Differences were more pronounced in the per-protocol analysis. Sodium oxybate was generally well tolerated under dose adjustments (no treatment-related dropouts), but it induced de novo obstructive sleep apnea in 2 patients and parasomnia in 1 patient, as detected by polysomnography, all of whom did not benefit from sodium oxybate treatment. Conclusions and Relevance: This study provides class I evidence for the efficacy of sodium oxybate in treating EDS and nocturnal sleep disturbance in patients with PD. Special monitoring with follow-up polysomnography is necessary to rule out treatment-related complications and larger follow-up trials with longer treatment durations are warranted for validation. Trial Registration: clinicaltrials.gov Identifier: NCT02111122.

Optimizing MSLT Specificity in Narcolepsy With Cataplexy.

Study Objectives: Multiple sleep onset rapid eye movement (R) periods (SOREMPs) and a mean sleep latency of ≤8 minutes on the multiple sleep latency test (MSLT) are diagnostic criteria of narcolepsy (NC), but also occur in other conditions with increased sleep pressure, including insufficient sleep syndrome (ISS), sleep-disordered breathing (SDB), or Parkinson's disease (PD). These false positives are common, may create diagnostic uncertainty, and highlight the need for complementary MSLT measures with high specificity for NC. Methods: Detailed analysis of MSLT findings in 56 NC, 83 PD, 89 SDB, and 23 ISS patients, using receiver operating characteristic curves. Results: A positive MSLT (mean sleep latency ≤ 8.0 minutes and ≥2 SOREMPs) was found in 53 NC (95%), 1 PD (1%), 8 SDB (9%), and 12 ISS patients (52%). MSLT-based differentiation between NC and non-NC patients was best when applying a mean R latency of ≤5 minutes (sensitivity/specificity/positive predictive value [PPV]: 49%/95%/96%) or a mean percentage of sleep stage R ≥ 40% (sensitivity/specificity/PPV: 60%/100%/100%) as cutoffs. When analyzing all 252 naps with SOREMPs in isolation, the combination of both R latency of ≤5 minutes and R percentage of ≥50% yielded a sensitivity/specificity/PPV of 50%/99%/99%. In addition, a sleep stage sequence with R occurring prior to N2 was more common in NC than in non-NC (71% vs. 32%, p < .001), and in combination with R percentage of ≥50% yielded a sensitivity/specificity/PPV of 53%/96%/97%. Conclusions: A better characterization of R sleep by latency, duration, and sleep stage sequence facilitates detection of false positives and, hence, contributes to a higher MSLT specificity in NC.

Electrophysiological Evidence for Alternative Motor Networks in REM Sleep Behavior Disorder.

Patients with Parkinson's disease (PD) and REM sleep behavior disorder (RBD) show mostly unimpaired motor behavior during REM sleep, which contrasts strongly to coexistent nocturnal bradykinesia. The reason for this sudden amelioration of motor control in REM sleep is unknown, however. We set out to determine whether movements during REM sleep are processed by different motor networks than movements in the waking state. We recorded local field potentials in the subthalamic nucleus (STN) and scalp EEG (modified 10/20 montage) during sleep in humans with PD and RBD. Time-locked event-related ß band oscillations were calculated during movements in REM sleep compared with movements in the waking state and during NREM sleep. Spectral analysis of STN local field potentials revealed elevated ß power during REM sleep compared with NREM sleep and ß power in REM sleep reached levels similar as in the waking state. Event-related analysis showed time-locked ß desynchronization during WAKE movements. In contrast, we found significantly elevated ß activity before and during movements in REM sleep and NREM sleep. Corticosubthalamic coherence was reduced during REM and NREM movements. We conclude that sleep-related movements are not processed by the same corticobasal ganglia network as movements in the waking state. Therefore, the well-known seemingly normal motor performance during RBD in PD patients might be generated by activating alternative motor networks for movement initiation. These findings support the hypothesis that pathological movement-inhibiting basal ganglia networks in PD patients are bypassed during sleep. SIGNIFICANCE STATEMENT: This study provides evidence that nocturnal movements during REM sleep in Parkinson's disease (PD) patients are not processed by the same corticobasal ganglia network as movements in the waking state. This implicates the existence of an alternative motor network that does not depend directly on the availability of l-Dopa in the basal ganglia. These findings further indicate that some PD patients are able to perform movements in the dopamine depleted state, possibly by bypassing the pathological basal ganglia network. The existence and direct activation of such alternative motor networks might finally have potential therapeutic effects for PD patients.

Brain iron deposition fingerprints in Parkinson's disease and progressive supranuclear palsy.

It can be difficult to clinically distinguish between classical Parkinson's disease (PD) and progressive supranuclear palsy. Previously, there have been no biomarkers that reliably allow this distinction to be made. We report that an abnormal brain iron accumulation is a marker for ongoing neurodegeneration in both conditions, but the conditions differ with respect to the anatomical distribution of these accumulations. We analyzed quantitative T2' maps as markers of regional brain iron content from PD and progressive supranuclear palsy patients and compared them to age-matched control subjects. T2-weighted and T2*-weighted images were acquired in 30 PD patients, 12 progressive supranuclear palsy patients, and 24 control subjects at 1.5 Tesla. Mean T2' values were determined in regions-of-interest in the basal ganglia, thalamus, and white matter within each hemisphere. The main findings were shortened T2' values in the caudate nucleus, globus pallidus, and putamen in progressive supranuclear palsy compared to PD patients and controls. A stepwise linear discriminant analysis allowed progressive supranuclear palsy patients to be distinguished from PD patients and the healthy controls. All progressive supranuclear palsy patients were correctly classified. No progressive supranuclear palsy patient was classified as a healthy control, no healthy controls were incorrectly classified as having progressive supranuclear palsy, and only 6.7% of the PD patients were incorrectly classified as progressive supranuclear palsy. Regional decreases of T2' relaxation times in parts of the basal ganglia reflecting increased brain iron load in these areas are characteristic for progressive supranuclear palsy but not PD patients.