Age related cerebrospinal fluid flow dynamics in the subarachnoid space of the optic nerve in patients with normal tension glaucoma, measured by diffusion weighted MRI.

BACKGROUND/OBJECTIVES: We aimed to measure cerebrospinal fluid (CSF) flow rates in the subarachnoid space (SAS) of the optic nerve (ON) by applying non-invasive diffusion-weighted MRI in patients with normal tension glaucoma (NTG) compared to age-matched controls. SUBJECTS/METHODS: In this prospective study, an analysis of diffusion-weighted images of 26 patients with NTG (49ONs) and age-matched volunteers (52ONs) was conducted. Subjects were classified into 4 groups: group I (50-59 y., n = 12 eyes), group II (60-69 y., n = 16 eyes), group III (70-79 y., n = 18 eyes) and group IV ( > 80 y., n = 6 eyes) for NTGs and healthy volunteers, respectively. The flow-range ratio (FRR) between the frontal lobe SAS and the SAS of the ON was calculated for each age category group and then compared between age-categories as well as between NTGs and controls. RESULTS: The mean FRR for age groups were (I) 0.54 ± 0.06 and 0.62 ± 0.03 (p < 0.05), (II) 0.56 ± 0.08 and 0.63 ± 0.03 (p < 0.05), (III) 0.54 ± 0.06 and 0.62 ± 0.02 (p < 0.001) as well as (IV) 0.61 ± 0.03 and 0.61 ± 0.04, for NTGs and controls, respectively. Using pooled data, the difference between the FRR in NTGs and controls was statistically significant (p < 0.0001). There were no statistically significant differences within the age categories of the control group. When comparing the FRR of NTGs by age categories, no statistically significant difference was found between the subgroups. CONCLUSIONS: FRR was significantly reduced in NTGs compared to age-matched controls without any significant differences within the age groups themselves. Given the physiological importance of CSF for the integrity of neurons, axons and glial cells, reduced CSF flow dynamics might be part of the underlying neurodegenerative process of NTG.

AGGREGATIBACTER ENDOPHTHALMITIS IN A PATIENT WITH DENTOPHOBIA.

PURPOSE: To describe a rare case of unilateral, endogenous endophthalmitis caused by Aggregatibacter aphrophilus (HACEK group) confirmed in vitreous and blood cultures, in a patient with dentophobia. METHODS: Case report. PATIENTS: A seventy-five-year-old male patient with Type 2 diabetes, previous myocardial infarction, and pacemaker implantation. RESULTS: Patient was observed with sudden loss of vision at the Department of Ophthalmology, Uppsala University. Initial diagnosis was posterior vitreous detachment and anterior uveitis, but progression of disease led to vitrectomy, which actually demonstrated endophthalmitis and growth of A. aphrophilus of the HACEK group. Aggregatibacter bacteremia and pacemaker endocarditis were also identified and dental examination confirmed growth of Aggregatibacter in the oral cavity. Intravitreal treatment with ceftazidime and vancomycin according to Endophthalmitis Vitrectomy Study protocol was administered with quick resolution of endophthalmitis. CONCLUSION: Aggregatibacter endophthalmitis is a rare, but devastating cause of vision loss where immediate diagnosis may be delayed. Prompt diagnosis may be facilitated by a thorough medical history and early vitreous biopsy. Systemic investigation by an infectious disease specialist and multidisciplinary assessment are mandatory. Ophthalmologic treatment is effective with intravitreal injections of ceftazidime and vancomycin.

Elevated perioptic lipocalin-type prostaglandin D synthase concentration in patients with idiopathic intracranial hypertension.

The pathophysiology of vision loss and loss of visual field in patients with idiopathic intracranial hypertension with papilloedema is not fully understood. Although elevated CSF pressure induces damage to the optic nerve due to stasis of axoplasmic flow, there is no clear relationship between the severity of papilloedema and CSF pressure. Furthermore, there are cases of purely unilateral papilloedema and cases without papilloedema despite significantly elevated intracranial pressure as well as papilloedema that can persist despite a successfully lowered intracranial pressure. We hypothesize that at least in some of such cases, in addition to purely pressure-induced damage to the optic nerve, the biochemical composition of the CSF in the subarachnoid space surrounding the orbital optic nerve may play a role in the pathogenesis of vision loss. In this retrospective study, we report on lipocalin-type prostaglandin D synthase concentrations in the CSF within the perioptic and lumbar subarachnoid space in 14 patients with idiopathic intracranial hypertension (13 females, mean age 45 ± 13 years) with chronic persistent papilloedema resistant to maximum-tolerated medical therapy and visual impairment. CSF was collected from the subarachnoid space of the optic nerve during optic nerve sheath fenestration and from the lumbar subarachnoid space at the time of lumbar puncture. CSF was analysed for lipocalin-type prostaglandin D synthase and the concentrations compared between the two sites using nephelometry. The mean lipocalin-type prostaglandin D synthase concentration in the perioptic subarachnoid space was significantly higher compared with the concentration in the lumbar subarachnoid space (69 ± 51 mg/l without correction of serum contamination and 89 ± 67 mg/l after correction of serum contamination versus 23 ± 8 mg/l; P < 0.0001, Mann-Whitney U-test). These measurements demonstrate a change and imbalance in the biochemical environment of the optic nerve. Its possible effect is discussed.

Case Report: Cerebrospinal Fluid Dynamics in the Optic Nerve Subarachnoid Space and the Brain Applying Diffusion Weighted MRI in Patients With Idiopathic Intracranial Hypertension-A Pilot Study.

Purpose: The aim of this study was to examine the cerebrospinal fluid (CSF) flow rates in the subarachnoid space (SAS) of the optic nerve (ON) and the brain in patients with idiopathic intracranial hypertension (IIH) and papilledema (PE) compared to healthy controls by applying non-invasive diffusion-weighted MRI. Methods: A retrospective analysis of diffusion-weighted MR images of 5 patients with IIH (10 ONs), mean age: 31 ± 10 years (5 women), and 11 healthy controls (22 ONs, mean age: 60 ± 13 years, 5 women) was performed. The flow velocity flow-range ratio (FRR) between the intracranial cavity and the SAS of the ON was calculated in both groups and then compared. Results: The mean FRR was 0.55 ± 0.08 in patients with IIH and 0.63 ± 0.05 in healthy controls. The difference between patients with IIH and healthy controls was statistically significant (p < 0.05). Conclusions: The CSF flow velocity was decreased in patients with IIH with PE compared to healthy controls. The reduced CSF flow dynamics might be involved in the pathophysiology of PE in IIH and diffusion-weighted MRI can be a useful non-invasive tool to study the CSF flow dynamics within the SAS ON. Summary: Idiopathic intracranial hypertension is a neurological disease, where vision loss is the most feared complication of this disorder. The pathophysiology of IIH is not fully understood but is strongly linked to a reduced uptake of CSF into the central dural sinus veins. In this study, we examined the CSF flow rates in the SAS ON and the brain in patients with IIH and PE compared to healthy controls by applying non-invasive diffusion-weighted MRI. Knowing about the flow ratio of CSF may be of clinical relevance for the treatment decisions of IIH. If medical treatment fails, surgical options for lowering the ICP pressure need to be taken into consideration. As the primary goal of treatment is to prevent the loss of vision and visual field, it is important to know whether the communication of CSF between the intracranial CSF and the CSF in the perioptic space is intact. We showed that the CSF flow velocity was decreased in IIH patients with PE compared to healthy controls. The reduced CSF flow might be involved in the pathophysiology of PE in IIH, and diffusion-weighted MRI can be a useful non-invasive tool to study the CSF flow dynamics within the SAS ON.

Lipocalin-type Prostaglandin D Synthase Concentration Gradients in the Cerebrospinal Fluid in Normal-tension Glaucoma Patients with Optic Nerve Sheath Compartmentation.

OBJECTIVE: To report on the lipocalin-type prostaglandin D synthase (L-PGDS) concentrations in the cerebrospinal fluid (CSF) of the perioptic and lumbar subarachnoid space (SAS) in patients with radiologically proven optic nerve (ON) sheath compartmentation presenting as normal-tension glaucoma (NTG). METHODS: Retrospective biochemical analysis of CSF in thirteen patients with ON sheath compartmentation presenting as NTG (four females, mean age 70±8 years). CSF was sampled from the SAS of the ON during ON sheath fenestration for ON sheath compartmentation and from the lumbar SAS at the time of lumbar puncture. Nephelometry was used for the quantification of L-PGDS and albumin concentration. Albumin was measured in order to assess the amount of contamination with serum in the CSF samples taken from the ON SAS. Main outcome measures were L-PGDS concentrations in the CSF of the perioptic and lumbar SAS. RESULTS: Mean L-PGDS concentration was 24±8 mg/L in the lumbar SAS compared to 33±27 mg/L without correction of serum contamination and 45±39 mg/L after correction of serum contamination in the perioptic SAS. The difference between the lumbar and the perioptic SAS was statistically significant (P=0.0047 without correction of serum contamination, P=0.0002 with correction of serum contamination; Mann-Witney U-test). CONCLUSION: This study demonstrates a concentration gradient of L-PGDS levels within the CSF with a statistically significant higher concentration in the compartmentalized perioptic SAS compared to that in the lumbar SAS. Biochemical changes in the perioptic SAS might be involved in the pathophysiology in NTG patients with ON sheath compartmentation.

Left orbital compartment syndrome and right anterior ischemic optic neuropathy in a patient with severe burns despite non-aggressive fluid resuscitation.

INTRODUCTION: Ophthalmological complications such as orbital compartment syndrome (OCS) and ischemic optic neuropathy are rare complications in patients with burns and have been described in patients where aggressive fluid resuscitation was performed. While OCS requires urgent surgical intervention, no current treatment is established to treat, or prevent, ischemic optic neuropathy in patients with burns. METHODS: The authors report a case of a 38-year-old woman with flame burns including the periorbital regions who developed OCS on the left side and anterior ischemic optic neuropathy (AION) on the right side despite non-aggressive fluid resuscitation. Immediate lateral canthotomy combined with inferior cantholysis was performed on the left side. DISCUSSION AND CONCLUSION: OCS and AION need to be considered as potential complications even in critically ill patients with facial burns who do not receive aggressive fluid resuscitation. Whether an early surgical intervention will lower the risk of AION development is, however, speculative. LAY SUMMARY: Ophthalmological complications such as orbital compartment syndrome and ischemic optic neuropathy are rare complications in patients with burns and have been described in patients where aggressive fluid resuscitation was performed. We present a case of a critically ill patient with severe facial burns who developed orbital compartment syndrome on the left side and anterior ischemic optic neuropathy on the right side even though our patient did not receive aggressive fluid resuscitation.Our case is particular because both of these rare complications are seen in a single patient and neither received aggressive fluid resuscitation. The fact that the patient did not develop ischemic optic neuropathy on the side where the lateral canthotomy was performed (only on the side where the patient had orbital compartment syndrome), this case might raise the discussion of whether an early surgical intervention might lower the risk of ischemic optic neuropathy development in patients with facial burns.

Brain activation patterns in medicated versus medication-naïve adults with attention-deficit hyperactivity disorder during fMRI tasks of motor inhibition and cognitive switching.

BACKGROUND: Adult-attention-deficit-hyperactive-disorder (ADHD) is often unrecognized condition. FMRI examination along with neuropsychological testing might strengthen the diagnosis. We hypothesized that ADHD-adults with and without medication would show different fMRI pattern compared to healthy controls while testing tasks of motor inhibition and cognitive switching. METHODS: 45 subjects in three age-matched groups: (1) controls, (2) ADHD-adults under medication (ADHD+) and (3) medication-naïve adults with ADHD (ADHD-) underwent fMRI and neuropsychological testing. Group analysis and population-based statistics were performed. RESULTS: DTVP-A, intellectual ability as well as attention capability, visual-perceptual and visual-motor abilities showed no significant differences between the groups. However, fMRI revealed statistically significant differences between the ADHD+, ADHD- and control groups on tasks of motor inhibition and cognitive switching on adults in bilateral fronto-striatal brain regions, inferior fronto-frontal, fronto-cingulate and fronto-parietal networks as well as in the parietal lobe (p < 0.05). CONCLUSIONS: fMRI offers the potential to differentiate between the ADHD+, ADHD- and control groups. FMRI possibly opens a new window for monitoring the therapeutic effect of ADHD medication. TRIAL REGISTRATION: NCT02578342, registered at August 2015 to clinical trial registry ( https://ichgcp.net/clinical-trials-registry/NCT02578342 ).

Cerebrospinal fluid and optic nerve sheath compartment syndrome: A common pathophysiological mechanism in five different cases?

IMPORTANCE: Optic nerve (ON) dysfunction is a common feature of different diseases. The pathophysiology is not yet fully understood. BACKGROUND: This study describes five patients with ON sheath (ONS) compartment syndrome (ONSCS) and contributes to the hypothesis that impaired cerebrospinal fluid (CSF) flow can play a role in the development of ON dysfunction. DESIGN: Retrospective case series. PARTICIPANTS: Five patients with ONSCS were included in the study. METHODS: Elaboration of medical histories and clinical and diagnostic findings over a long time period was carried out by analysing medical records and by a detailed medical consultation. MAIN OUTCOME MEASURES: The main outcome measures include clinical history; visual acuity; field, intraocular and CSF pressures; and contrast-loaded computed tomographic (CT) cisternography. RESULTS: Compartmentation of the ONS demonstrated by contrast-loaded CT cisternography was the consistent finding in all five patients who demonstrated findings of ON dysfunction. The aetiologies varied and included meningitis, papilloedema, sphenoid wing meningioma, disc herniation and normal-tension glaucoma. CONCLUSION AND RELEVANCE: Compartmentation of the ONS with consecutively impaired CSF dynamics within the ON subarachnoid space can lead to ON dysfunction. Different aetiologies can cause the development of ONSCS.

Perioptic Cerebrospinal Fluid Dynamics in Idiopathic Intracranial Hypertension.

Purpose: To examine the cerebrospinal fluid (CSF) dynamics along the entire optic nerve in patients with idiopathic intracranial hypertension (IIH) and papilledema by computed tomographic (CT) cisternography. Methods: Retrospective analysis of CT cisternographies in 16 patients with a history of IIH and papilledema (14 females and 2 males, mean age: 49 ± 16 years). Contrast loaded CSF (CLCSF) was measured in Hounsfield Units (HU) at three defined regions of interest (ROI) along the optic nerve (orbital optic nerve portion: bulbar and mid-orbital segment, intracranial optic nerve portion) and additionally in the basal cistern. The density measurements in ROI 1, ROI 2, and ROI 3 consist of measurements of the optic nerve complex: optic nerve sheath, CLCSF filled SAS and optic nerve tissue. As controls served a group of patients (mean age: 60 ± 19 years) without elevated intracranial pressure and without papilledema. Results: In IIH patients the mean CLCSF density in the bulbar segment measured 65 ± 53 HU on the right and 63 ± 35 HU on the left side, in the mid-orbital segment 68 ± 37 HU right and 60 ± 21 HU left. In the intracranial optic nerve portion 303 ± 137 HU right and 323 ± 169 HU left and in the basal cistern 623 ± 188 HU. Within the optic nerve the difference of CLCSF density showed a highly statistical difference (p < 0.001) between the intracranial optic nerve portion and the mid-orbital segment. CLCSF density was statistically significantly (p < 0.001) reduced in both intraorbital optic nerve segments in patients with IIH compared to controls. Conclusions: The current study demonstrates reduced CLCSF density within the orbital optic nerve segments in patients with IIH and papilledema compared to 12 controls without elevated intracranial pressure and without papilledema. Impaired CSF dynamics could be involved in the pathophysiology of optic nerve damage in PE in IIH.

Impaired cerebrospinal fluid dynamics along the entire optic nerve in normal-tension glaucoma.

PURPOSE: To investigate the cerebrospinal fluid (CSF) dynamics along the entire optic nerve (ON) in patients with normal-tension glaucoma (NTG). METHODS: Retrospective analysis of computed tomographic (CT) cisternographies in Caucasian patients with NTG. Fifty-six patients (99 of 112 eyes) fulfilled the diagnostic criteria of NTG and underwent CT-cisternography. Twelve subjects without NTG (24 eyes) served as controls. Contrast-loaded cerebrospinal fluid (CLCSF) density measurements in Hounsfield units (HU) were performed at four defined regions along the ON and in the basal cistern. RESULTS: In NTG patients, the mean density CLCSF in the bulbar segment measured 76 ± 49 HU right and 88 ± 74 HU left, in the mid-orbital segment 117 ± 92 HU right and 119 ± 73 HU left, in the intracanalicular ON portion 209 ± 88 HU right and 216 ± 101 HU left, in the intracranial ON portion 290 ± 106 HU right and 286 ± 118 HU left and in the basal cistern 517 ± 213 HU. The distribution of CLCSF along the ON showed a statistically significant reduction in the intraorbital ON segments in NTG patients compared to controls without NTG with the far largest difference within the retrobulbar segment (-150 HU right and -117 HU left; right: p < 0.001, left: p < 0.001). CONCLUSION: This study demonstrates a gradual reduction in CLCSF towards the retrobulbar segment in NTG, while in controls without NTG, no reduction in CLCSF was measured within the orbital segments. Impaired CSF dynamics along the ON may contribute to the pathophysiology of NTG.

Flow dynamics of cerebrospinal fluid between the intracranial cavity and the subarachnoid space of the optic nerve measured with a diffusion magnetic resonance imaging sequence in patients with normal tension glaucoma.

IMPORTANCE: This study offers a new approach for the quantification of CSF dynamics. BACKGROUND: Non-invasive method to quantify the CSF dynamics in the subarachnoid space of the optic nerve is highly desirable. The aim of the study was to measure slow-flow CSF velocities in healthy controls and normal tension glaucoma patients between the intracranial cavity and the subarachnoid space of the optic nerve. DESIGN: Prospective observational study. PARTICIPANTS: Eleven age-matched healthy volunteers and 15 normal tension glaucoma patients. METHODS: Using phase contrast images, the phase shift in MRI diffusion images can be used to determine the flow velocity. Flow-range ratio between the intracranial cavity and the subarachnoid space of the optic nerve was calculated. MAIN OUTCOME MEASURE: Flow-range ratio between the intracranial cavity and the subarachnoid space of the optic nerve was calculated. RESULTS: First, phantom measurements were provided to validate the slow-flow velocity calculations. Second, flow-range ratio was validated for the healthy controls (0.63 ± 0.05), with the range being similar for the right and left optic nerve (P = 0.1). Statistically significant results were obtained (P < 0.05) when comparing the flow-range ratio in the optic nerve of healthy controls (n = 22 eyes, 0.63 ± 0.05) with the flow-range ratio in pathological optic nerves (n = 23, 0.55 ± 0.08) of normal tension glaucoma patients. MANOVA revealed no dependency between flow-range ratio and patient dependent variables. CONCLUSION AND RELEVANCE: Diffusion-weighted imaging provides a method to evaluate CSF flow within the subarachnoid space of the optic nerve in a non-invasive manner. Compared to healthy controls, patients with normal tension glaucoma measure a significantly lower flow-range ratio. This finding suggests a possible role of impaired CSF dynamics in the pathophysiology in normal tension glaucoma.