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Purpose of ReviewA pressure difference between the intraocular and intracranial compartments at the site of the lamina cribrosa has been hypothesized to have a pathophysiological role in several optic nerve head diseases. This paper reviews the current literature on the translamina cribrosa pressure difference (TLCPD), the associated pressure gradient, and its potential pathophysiological role, as well as the methodology to assess TLCPD.Recent FindingsFor normal-tension glaucoma (NTG), initial studies indicated low intracranial pressure (ICP) while recent findings indicate that a reduced ICP is not mandatory.SummaryData from studies on the elevated TLCPD as a pathophysiological factor of NTG are equivocal. From the identification of potential postural effects on the cerebrospinal fluid (CSF) communication between the intracranial and retrolaminar space, we hypothesize that the missing link could be a dysfunction of an occlusion mechanism of the optic nerve sheath around the optic nerve. In upright posture, this could cause an elevated TLCPD even with normal ICP and we suggest that this should be investigated as a pathophysiological component in NTG patients.

Purpose To evaluate the effect of intracameral air on intraocular pressure (IOP) measurements using Goldmann applanation tonometry (GAT) and applanation resonance tonometry (ART) in an in-vitro porcine eye model. Methods IOP was measured on thirteen freshly enucleated eyes at three reference pressures: 20, 30, and 40 mmHg. Six measurements/method were performed in a standardized order with GAT and ART respectively. Air was injected intracamerally in the same manner as during Descemet’s stripping endothelial keratoplasty (DSEK) and Descemet’s membrane endothelial keratoplasty (DMEK), and the measurements were repeated. Results Measured IOP increased significantly for both tonometry methods after air injection: 0.7 ± 2.1 mmHg for GAT and 10.6 ± 4.9 mmHg for ART. This difference was significant at each reference pressure for ART but not for GAT. Conclusions Although slightly affected, this study suggests that we can trust GAT IOP-measurements in eyes with intracameral air, such as after DSEK/DMEK operations. Ultrasound-based methods such as ART should not be used.

The laminin composition (LMalpha1-alpha5, beta1-beta3, gamma1 and gamma2 chains) of normal corneas and corneal buttons from keratoconus, bullous keratopathy (BKP), Fuchs' dystrophy + BKP, Fuchs' dystrophy without BKP and scar after deep lamellar keratoplasty (DLKP) was investigated with immunohistochemistry. The epithelial basement membranes (BMs) of both normal and diseased corneas contained LMalpha3, alpha5, beta1, beta3, gamma1 and gamma2 chains. The epithelial BM morphology was altered in the different diseases. Scarring was associated with irregular BM and ectopic stromal localization of different laminin chains. The Descemet's membrane (DM) contained LMalpha5, beta1 and gamma1 chains in all cases and additionally LMbeta3 and gamma2 chains in the majority of keratoconus corneas. The interface in the DLKP cornea had patches of LMalpha3, alpha4, alpha5, beta1 and beta2 chains, and an extra BM-like structure under the Bowman's membrane. These results suggest that laminin chains participate in the process of corneal scarring and in the pathogenesis of some corneal diseases. The novel finding of LMalpha3, beta3 and gamma2 in the DM of keratoconus buttons indicates that this membrane is also involved in the disease and that some cases of keratoconus may have a congenital origin, without normal downregulation of the LMbeta3 chain.

Clinical rating scales for tremors have significant limitations due to low resolution, high rater dependency, and lack of applicability in outpatient settings. Reliable, quantitative approaches for assessing tremor severity are warranted, especially evaluating treatment effects, e.g., of deep brain stimulation (DBS). We aimed to investigate how different accelerometry metrics can objectively classify tremor amplitude of Essential Tremor (ET) and tremor in Parkinson’s Disease (PD). We assessed 860 resting and postural tremor trials in 16 patients with ET and 25 patients with PD under different DBS settings. Clinical ratings were compared to different metrics, based on either spectral components in the tremorband or pure acceleration, derived from simultaneous triaxial accelerometry captured at the index finger and wrist. Nonlinear regression was applied to a training dataset to determine the relationship between accelerometry and clinical ratings, which was then evaluated in a holdout dataset. All of the investigated accelerometry metrics could predict clinical tremor ratings with a high concordance (>70%) and substantial interrater reliability (Cohen’s weighted Kappa > 0.7) in out-of-sample data. Finger-worn accelerometry performed slightly better than wrist-worn accelerometry. We conclude that triaxial accelerometry reliably quantifies resting and postural tremor amplitude in ET and PD patients. A full release of our dataset and software allows for implementation, development, training, and validation of novel methods.

Background Cognitive impairment is common in Parkinson’s disease (PD). Up to 80% of people with PD develop dementia over the disease course, heavily impacting their quality of life. While pharmacological treatment options are scarce, previous research highlights the potential benefits of non-pharmacological interventions, such as cognitive training (CT), on cognition and non-cognitive outcomes. This study’s purpose is to examine the feasibility as well as short- and long-term effects of a 5-week digital CT in people with advanced PD, compared to people with advanced PD receiving care as usual, and to explore possible predictors of CT responsiveness. Methods This ongoing monocentric, two-armed randomized controlled trial (RCT) seeks to include 140 participants with advanced PD according to the established 5-2-1 criteria. Participants are randomized into either the experimental group, receiving a structured 5-week digital CT and additional psychoeducational videos on cognitive health, or a passive control group receiving care as usual. CT will be carried out remotely from home and supervised by the study team. Feasibility will be assessed using a training diary (e.g., motivation, satisfaction) and technical data (e.g., training duration). Neuropsychological assessments will be carried out pre- and post-CT and after a 3-month follow-up period. The primary outcome will be global cognition measured with the Montréal Cognitive Assessment (MoCA). Secondary outcomes include further cognitive, motor, and (neuro)psychological variables (e.g., quality of life, motor symptoms, mood, activities of daily living). Discussion Studies on CT in people with PD have demonstrated positive effects on cognition, promoting the application of CT as a non-pharmacological treatment approach. However, studies targeting people in more advanced PD stages are rare or non-existent, despite it being a clinically relevant target group. Further, few studies have looked at long-term CT effects in PD, and very little data exists regarding CT predictors. Therefore, this large-cohort study of a multi-domain digital CT in people with advanced PD aims to provide insights into the effects, feasibility, and acceptability of CT within a representative sample of people with PD, allowing for statistically high-powered analyses and the identification of potential CT predictors. Trial registration German Clinical Trials Register (DRKS) DRKS00028876. Registered on 21 November 2022

AIMS To compare the effect on intraocular pressure (IOP) of latanoprost applied once daily with four times daily and to study if the difference persisted when treatment changed to once daily. METHODS IOP was followed in 28 healthy volunteers in a double masked randomised 52 day study. Latanoprost 50 μg/ml was administered once daily in one eye and four times daily in the other during 2 weeks. Subsequently both eyes received one daily drop for 2 weeks. After another 3 weeks without treatment, a single drop was instilled in each eye. RESULTS The IOP reduction on days 2 and 3 was greater in the eyes treated with four daily doses (p<0.01). During the following period there were no statistically significant differences between the eyes. After 3 weeks without treatment the IOP was lower than pretreatment (p<0.001). A single dose of latanoprost on day 50 resulted in a similar decrease in IOP in both eyes. Transient photophobia, mild flare, and/or a few cells occurred in 15 subjects. Two subjects were withdrawn because of photophobia and/or signs of anterior uveitis. CONCLUSION Latanoprost four times daily caused an IOP reducing effect which was similar to once daily dosing, except for the first 2 days of treatment when it was more effective. Transient photophobia, cells, and flare were common during the four dose regimen, but resolved spontaneously without cessation of treatment.

Applanation resonance tonometry (ART) has been shown in a number of studies to be useful for measuring intraocular pressure (IOP). Data from in vitro laboratory bench testing, where the sensor was carefully centralised onto the cornea, has been very consistent with good precision in the determination of IOP. However, in a clinical study the unavoidable off-centre placement of the sensor against the cornea resulted in a reduced precision. The aim of this study was to evaluate a new design of the sensor with a symmetric sensor probe and a contact piece with a larger diameter. Two in vitro porcine eye experimental set-ups were used. One bench-based for examining position dependence and one biomicroscope-based set-up, simulating a clinical setting, for evaluating IOP(ART) precision at seven different pressure levels (1040 mmHg), set by connecting a saline column to the vitreous chamber. The reference IOP was recorded using a pressure transducer. There was no significant difference between four positions 1 mm off centre and the one centre position. The precision of the ART as compared with the reference pressure was +/- 1.03 mmHg (SD, n = 42). The design improvement has enhanced the precision of the ART in the biomicroscope set-up to be in parity with bench test results from a set-up using perfect positioning. This indicates that off-centre positioning was no longer a major contributor to the deviations in measured IOP. The precision was well within the limits set by ISO standard for eye tonometers. Therefore, a larger in vivo study on human eyes with the ART should be performed.

Gilles de la Tourette Syndrome (GTS) is a chronic tic disorder, characterized by unwanted motor actions and vocalizations. While brain stimulation techniques show promise in reducing tic severity, optimal target networks are not well-defined. Here, we leverage datasets from two independent deep brain stimulation (DBS) cohorts and a cohort of tic-inducing lesions to infer critical networks for treatment and occurrence of tics by mapping stimulation sites and lesions to a functional connectome derived from 1,000 healthy participants. We find that greater tic reduction is linked to higher connectivity of DBS sites (N = 37) with action-related functional resting-state networks, i.e., the cingulo-opercular (r = 0.62; p < 0.001) and somato-cognitive action networks (r = 0.47; p = 0.002). Regions of the cingulo-opercular network best match the optimal connectivity profiles of thalamic DBS. We replicate the significance of targeting cingulo-opercular and somato-cognitive action network connectivity in an independent DBS cohort (N = 10). Finally, we demonstrate that tic-inducing brain lesions (N = 22) exhibit similar connectivity to these networks. Collectively, these results suggest a critical role for these action-related networks in the pathophysiology and treatment of GTS. By leveraging diverse datasets from brain stimulation therapy for Tourette Syndrome and tic-inducing brain lesions, Baldermann et al. reveal a critical role of action-related functional networks in both the treatment and pathophysiology of tic disorders.

Background Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established treatment for Parkinson’s disease (PD). Beyond basic omnidirectional, monopolar stimulation, advanced stimulation settings (AS), such as directional or vertical current steering, variation of pulse width and frequency, bipolar and interleaving stimulation are increasingly available. Our aim was to summarize current evidence on AS in STN-DBS in PD and systemically report their application and potential benefits in clinical routine. Methods In this retrospective single-center observational study, we analyzed stimulation settings of 145 patients with bilateral STN-DBS 3, 6, and 12 months postoperatively. Secondary outcomes included preoperative levodopa response, lead positions, and postoperative reduction of levodopa-equivalent daily dose (LEDD) in patients staying with basic stimulation settings (BS) compared to those initially with AS at 3-months follow-up and those with a change from BS to AS. Results AS were applied in 40.7%, 55.9%, and 73.8% of patients at 3, 6, and 12 months respectively. LEDD reduction after three months was higher in patients remaining with BS or initially AS than in patients with a switch to AS after three months, while there was no difference at 12 months. Median distance of leads to the center of gravity of the motor-STN was slightly larger when AS were applied. Conclusions AS are frequently employed in clinical routine at a specialized DBS center. They may compensate for deviant lead placement in terms of stimulation efficacy measured by postoperative LEDD reduction. Prospective studies are warranted, focusing on specific AS indications in chronic DBS to optimize individual patient outcomes.

Intragastric botulinum neurotoxin injections (IBNI) are offered off-label in the private medical sector in a few European countries as a safe and effective weight-loss measure. In February and March 2023, an outbreak of iatrogenic botulism occurred in several European countries following IBNI treatment in Turkey. This case series describes the clinical features of severe iatrogenic botulism after IBNI. We retrospectively summarize the clinical course and emergency department and intensive care unit interventions in ten cases of severe iatrogenic botulism that occurred after receiving IBNI in this sudden outbreak in Austria and Germany. Seven out of ten cases initially showed characteristic symptoms of botulism with diplopia, dysphagia, dysarthria, dysarthrophonia, and descending paralysis. All patients were hospitalized, six in an intensive care unit and partially requiring mechanical ventilation. All patients recovered and were discharged without relevant permanent deficits. Our study highlights ten clinical cases in this iatrogenic botulism outbreak, representing the largest reported outbreak worldwide. Clinicians should be aware of the risks associated with medical procedures involving botulinum neurotoxins and ensure measures to minimize the risk of iatrogenic botulism.