Lasse Malmqvist

Peripapillary Retinal Nerve Fiber Layer Thickness Corresponds to Drusen Location and Extent of Visual Field Defects in Superficial and Buried Optic Disc Drusen

Background: Optic disc drusen (ODD) are hyaline deposits located within the optic nerve head. Peripapillary retinal nerve fiber layer (RNFL) thinning is associated with the high prevalence of visual field defects seen in ODD patients. The goal of this study was to investigate the characteristics of patients with ODD and to compare the peripapillary RNFL thickness to the extent of visual field defects and anatomic location (superficial or buried) of ODD. Methods: Retrospective, cross sectional study. Results: A total of 149 eyes of 84 ODD patients were evaluated. Sixty-five percent were female and 76% had bilateral ODD. Of 149 eyes, 109 had superficial ODD and 40 had buried ODD. Peripapillary RNFL thinning was seen in 83.6% of eyes, where optical coherence tomography was performed (n = 61). Eyes with superficial ODD had greater mean peripapillary RNFL thinning (P ⩽ 0.0001) and visual field defects (P = 0.002) than eyes with buried ODD. There was a correlation between mean peripapillary RNFL thinning and visual field defects as measured by perimetric mean deviation (R-0.66; P = 0.0001). The most frequent visual field abnormalities were arcuate and partial arcuate defects. Conclusions: Peripapillary RNFL thickness correlates with anatomic location (superficial or buried) of ODD. Frequency and extent of visual field defects corresponded with anatomic location of ODD and peripapillary RNFL thickness, suggesting increased axonal damage in patients with superficial ODD.

Cardiac arrhythmias the first month after acute traumatic spinal cord injury.

Abstract Objective Cardiovascular complications including cardiac arrest and arrhythmias remain a clinical challenge in the management of acute traumatic spinal cord injury (SCI). Still, there is a lack of knowledge regarding the characteristics of arrhythmias in patients with acute traumatic SCI. The aim of this prospective observational study was to investigate the occurrence of cardiac arrhythmias and cardiac arrests in patients with acute traumatic SCI. Methods As early as possible after SCI 24-hour Holter monitoring was performed. Additional Holter recordings were performed 1, 2, 3, and 4 weeks after SCI. Furthermore, 12-lead electrocardiograms (ECGs) were obtained shortly after SCI and at 4 weeks. Results Thirty patients were included. Bradycardia (heart rate (HR) <50 b.p.m.) was present in 17–35% of the patients with cervical (C1–C8) SCI (n = 24) within the first 14 days. In the following 14 days, the occurrence was 22–32%. Bradycardia in the thoracic (Th1–Th12) SCI group (n = 6) was present in 17–33% during the observation period. The differences between the two groups were not statistically significant. The mean minimum HR was significantly lower in the cervical group compared with the thoracic group both on 12-lead ECGs obtained shortly after SCI (P = 0.030) and at 4 weeks (P = 0.041). Conclusion Many patients with cervical SCI experience arrhythmias such as bradycardia, sinus node arrest, supraventricular tachycardia, and more rarely cardiac arrest the first month after SCI. Apart from sinus node arrests and limited bradycardia, no arrhythmias were seen in patients with thoracic SCI. Standard 12-lead ECGs will often miss the high prevalence these arrhythmias have.

Autonomic Dysfunction in Patients with Mild to Moderate Alzheimer’s Disease

BACKGROUND Autonomic function has received little attention in Alzheimers disease (AD). AD pathology has an impact on brain regions which are important for central autonomic control, but it is unclear if AD is associated with disturbance of autonomic function. OBJECTIVE To investigate autonomic function using standardized techniques in patients with AD and healthy age-matched controls. METHOD Thirty-three patients with mild to moderate AD and 30 age- and gender-matched healthy controls, without symptoms of autonomic dysfunction, underwent standardized autonomic testing with deep breathing, Valsalva maneuver, head-up tilt, and isometric handgrip test. Brachial pressure curve and electrocardiogram were recorded for off-line analysis of blood pressure and beat-to-beat heart rate (HR). RESULTS AD patients had impaired blood pressure responses to Vasalva maneuver (p < 0.0001) and HR response to isometric contraction (p = 0.0001). A modified composite autonomic scoring scale showed greater degree of autonomic impairment in patients compared to controls (patient: 2.1 ± 1.6; controls: 0.9 ± 1.1, p = 0.001). HR response to deep breathing and Valsalva ratio were similar in the two groups. CONCLUSION We identified autonomic impairment ranging from mild to severe in patients with mild to moderate AD, who did not report autonomic symptoms. Autonomic impairment was mainly related to impairment of sympathetic function and evident by impaired blood pressure response to the Vasalva maneuver. The clinical implications of this finding are that AD may be associated with autonomic disturbances, but patients with AD may rarely report symptoms of autonomic dysfunction. Future research should systematically evaluate symptoms of autonomic function and characterize risk factors associated with autonomic dysfunction.

Quantitatively Measured Anatomic Location and Volume of Optic Disc Drusen: An Enhanced Depth Imaging Optical Coherence Tomography Study

Purpose Optic disc drusen (ODD) are found in up to 2.4% of the population and are known to cause visual field defects. The purpose of the current study was to investigate how quantitatively estimated volume and anatomic location of ODD influence optic nerve function. Methods Anatomic location, volume of ODD, and peripapillary retinal nerve fiber layer and macular ganglion cell layer thickness were assessed in 37 ODD patients using enhanced depth imaging optical coherence tomography. Volume of ODD was calculated by manual segmentation of ODD in 97 B-scans per eye. Anatomic characteristics were compared with optic nerve function using automated perimetric mean deviation (MD) and multifocal visual evoked potentials. Results Increased age (P = 0.015); larger ODD volume (P = 0.002); and more superficial anatomic ODD location (P = 0.007) were found in patients with ODD visible by ophthalmoscopy compared to patients with buried ODD. In a multivariate analysis, a worsening of MD was significantly associated with larger ODD volume (P < 0.0001). No association was found between MD and weighted anatomic location, age, and visibility by ophthalmoscopy. Decreased ganglion cell layer thickness was significantly associated with worse MD (P = 0.025) and had a higher effect on MD when compared to retinal nerve fiber layer thickness. Conclusions Large ODD volume is associated with optic nerve dysfunction. The worse visual field defects associated with visible ODD should only be ascribed to larger ODD volume and not to a more superficial anatomic ODD location.

The Optic Disc Drusen Studies Consortium Recommendations for Diagnosis of Optic Disc Drusen Using Optical Coherence Tomography

Background: Making an accurate diagnosis of optic disc drusen (ODD) is important as part of the work-up for possible life-threatening optic disc edema. It also is important to follow the slowly progressive visual field defects many patients with ODD experience. The introduction of enhanced depth imaging optical coherence tomography (EDI-OCT) has improved the visualization of more deeply buried ODD. There is, however, no consensus regarding the diagnosis of ODD using OCT. The purpose of this study was to develop a consensus recommendation for diagnosing ODD using OCT. Methods: The members of the Optic Disc Drusen Studies (ODDS) Consortium are either fellowship trained neuro-ophthalmologists with an interest in ODD, or researchers with an interest in ODD. Four standardization steps were performed by the consortium members with a focus on both image acquisition and diagnosis of ODD. Results: Based on prior knowledge and experiences from the standardization steps, the ODDS Consortium reached a consensus regarding OCT acquisition and diagnosis of ODD. The recommendations from the ODDS Consortium include scanning protocol, data selection, data analysis, and nomenclature. Conclusions: The ODDS Consortium recommendations are important in the process of establishing a reliable and consistent diagnosis of ODD using OCT for both clinicians and researchers.

Alterations in cardiac autonomic control in spinal cord injury

A spinal cord injury (SCI) interferes with the autonomic nervous system (ANS). The effect on the cardiovascular system will depend on the extent of damage to the spinal/central component of ANS. The cardiac changes are caused by loss of supraspinal sympathetic control and relatively increased parasympathetic cardiac control. Decreases in sympathetic activity result in heart rate and the arterial blood pressure changes, and may cause arrhythmias, in particular bradycardia, with the risk of cardiac arrest in those with cervical or high thoracic injuries. The objective of this review is to give an update of the current knowledge related to the alterations in cardiac autonomic control following SCI. With this purpose the review includes the following subheadings: 2. Neuro-anatomical plasticity and cardiac control 2.1 Autonomic nervous system and the heart 2.2 Alteration in autonomic control of the heart following spinal cord injury 3. Spinal shock and neurogenic shock 3.1 Pathophysiology of spinal shock 3.2 Pathophysiology of neurogenic shock 4. Autonomic dysreflexia 4.1 Pathophysiology of autonomic dysreflexia 4.2 Diagnosis of autonomic dysreflexia 5. Heart rate/electrocardiography following spinal cord injury 5.1 Acute phase 5.2 Chronic phase 6. Heart rate variability 6.1 Time domain analysis 6.2 Frequency domain analysis 6.3 QT-variability index 6.4 Nonlinear (fractal) indexes 7. Echocardiography 7.1 Changes in cardiac structure following spinal cord injury 7.2 Changes in cardiac function following spinal cord injury 8. International spinal cord injury cardiovascular basic data set and international standards to document the remaining autonomic function in spinal cord injury.

Multifocal visual evoked potentials for quantifying optic nerve dysfunction in patients with optic disc drusen

To explore the applicability of multifocal visual evoked potentials (mfVEPs) for research and clinical diagnosis in patients with optic disc drusen (ODD). This is the first assessment of mfVEP amplitude in patients with ODD.

Long-term evolution of superficial optic disc drusen

Optic disc drusen (ODD) is hyaline deposits in the optic nerve head seen in 1–2% of the population. Long‐term evolution of ODD anatomy and visual field defects in ODD patients is a key factor for learning more about pathophysiology and prognosis of the condition. With a median follow‐up period of 56 years, this is the first study that evaluates superficial optic disc anatomy and visual fields in patients with ODD over a life span.

Optic disc drusen: understanding an old problem from a new perspective

Optic disc drusen (ODD) are acellular deposits located in the optic nerve head of up to 2.4% of the population. They may develop as by‐products of impaired axonal metabolism in genetically predisposed individuals, in whom a narrow scleral canal is hypothesized to play a role. Although ODD are often considered as benign innocent bystanders, recognized as part of a routine ophthalmological examination, the vast majority of patients with ODD have visual field defects. Optic disc drusen (ODD)‐associated complications with severe visual loss, most often due to anterior ischaemic optic neuropathy, are also known to occur. There are no treatments available to prevent or ameliorate the vision loss caused by ODD. In children, the ODD are usually uncalcified and buried within the optic nerve head tissue. In these cases, the condition can be difficult to diagnose, as it often resembles a papilloedema with optic nerve head swelling caused by raised intracranial pressure. During the teenage years, the ODD progressively become more calcified and probably also larger, which allow them to be visible on ophthalmoscopy. With the advent and proper utilization of high‐resolution modalities of optical coherence tomography (OCT), it has now become possible to detect even the smallest and most deeply located ODD. This allows for ODD detection at a much earlier developmental stage than has previously been possible and enhances the possibilities of research in underlying mechanisms. A review of the literature on ODD was conducted using the PUBMED database. The review focuses on the current knowledge regarding pathogenesis, diagnostics, clinical disease‐tracking methodologies, structure–function relationships and treatment strategies of ODD.

RE: Traber et al.: Enhanced depth imaging optical coherence tomography of optic nerve head drusen: a comparison of cases with and without visual field loss (Ophthalmology. 2017;124:66-73)

TO THE EDITOR: We read with interest the study by Traber et al, where the presence or absence of visual field defects was correlated with optic nerve head drusen (ONHD) morphology. The ONHD were classified using enhanced depth imaging optical coherence tomography (OCT) morphologic characteristics as either peripapillary, granular, or confluent. The hyperreflective structures classified as peripapillary ONHD in the present study have previously been labeled as ONHD; however, we do not find substantial evidence for this suggestion. First, we regularly see similar hyperreflective mass-like peripapillary changes in OCT volume scans of patients with papilledema from idiopathic intracranial hypertension, none of whom show other ONHD characteristics (Fig 1). In these patients, the peripapillary changes are thought to be secondary to axoplasmic stasis. Second, the “peripapillary drusen” also differ from recognized ONHD OCT morphology, having a hyperreflective core and no surrounding high-signal border. Furthermore, unlike classic ONHD, they extend across areas of the optic disc circumference corresponding to a blurring of the optic disc margin. If this blurring was caused by superficial ONHD, they should be visible on ophthalmoscopy and exhibit the typical hyporeflective core surrounded by hyperreflective bands on OCT. In the study by Traber et al, the authors found that none of the peripapillary structures exhibited autofluorescence and none were evident as drusen on ultrasound imaging. No histologic findings have shown a resemblance between these peripapillary structures and regular ONHD. The peripapillary structures have been diagnosed histologically as retinal scarring and, in contrast with ONHD, calcium is not found within them. The finding of endothelial lined channels in one of the retinal scars could indicate blood vessels, which are not found in ONHD. Although the lack of calcium in these peripapillary structures could be a result of immature ONHD, these structures are found in all age groups, including elderly patients in whom noncalcified drusen are not found elsewhere. It is thought traditionally that the more superficial ONHD are the more calcified, making it less likely that these structures are immature noncalcified ONHD. Although the authors acknowledge some doubt about classifying these changes as ONHD, they argue that the peripapillary changes should be considered ONHD, given that confluent ONHD were found within peripapillary subretinal structures. However, it is just as possible that ONHD developed in this area coincidentally. The authors suggest that the peripapillary structures may be an early form of ONHD, but this is inconsistent with the absence of similar structures where the vast majority of definite ONHD are found (within the substance of the optic nerve itself) and with the observation that the majority of these peripapillary structures do not contain any definite ONHD. In preliminary data from our own ONHD prospective cohort, some degree of peripapillary mass-like structure was found in 28 of 35 patients. In all 28 patients, the blurring of the optic disc corresponded with the peripapillary mass-like structures, which were seen in conjunction with regular ONHD. The authors suggest that the peripapillary changes could indicate axonal stasis as an early form of ONHD but we find no substantial evidence to diagnose these as ONHD, early ONHD, or even as a parallel form of ONHD, as proposed by Traber et al. Instead, they may be the result of axoplasmic stasis with disruption of retinal layers caused by nonspecific axonal compression. Until there is clarity about the etiology of these structures, we recommend classification systems avoid labeling them as ONHD unless further evidence becomes available.