Change in Morphological Features of Enlarged Subarachnoid Spaces Following Treatment in Idiopathic Normal Pressure Hydrocephalus.

BACKGROUND: Focally enlarged sulci (FES) are areas of proposed extraventricular fluid entrapment that may occur within idiopathic normal pressure hydrocephalus (iNPH) with radiographic evidence of disproportionately enlarged subarachnoid-space hydrocephalus (DESH), and should be differentiated from atrophy. PURPOSE: To evaluate for change in FES size and pituitary height after shunt placement in iNPH. STUDY TYPE: Retrospective. SUBJECTS: A total of 125 iNPH patients who underwent shunt surgery and 40 age-matched controls. FIELD STRENGTH/SEQUENCE: 1.5 T and 3 T. Axial T2w FLAIR, 3D T1w MPRAGE, 2D sagittal T1w. ASSESSMENT: FES were measured in three dimensions and volume was estimated by assuming an ellipsoid shape. Pituitary gland height was measured in the mid third of the gland in iNPH patients and controls. STATISTICAL TESTS: Wilcoxon signed-rank test for comparisons between MRI measurements; Wilcoxon rank sum test for comparison of cases/controls. Significance level was P < 0.05. RESULTS: Fifty percent of the patients had FES. FES volume significantly decreased between the pre and first postshunt MRI by a median of 303 mm3 or 30.0%. Pituitary gland size significantly increased by 0.48 mm or 14.4%. FES decreased significantly by 190 mm3 or 23.1% and pituitary gland size increased significantly by 0.25 mm or 6% between the first and last postshunt MRI. DATA CONCLUSION: Decrease in size of FES after shunt placement provides further evidence that these regions are due to disordered cerebrospinal fluid (CSF) dynamics and should not be misinterpreted as atrophy. A relatively smaller pituitary gland in iNPH patients that normalizes after shunt is a less-well recognized feature of altered CSF dynamics. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Spontaneous intracranial hypotension: updates from diagnosis to treatment.

Spontaneous intracranial hypotension (SIH) is caused by spinal cerebrospinal fluid (CSF) leaks, which result in continued loss of CSF volume and multiple debilitating clinical manifestations. The estimated annual incidence of SIH is 5/100,000. Diagnostic methods have evolved in recent years due to improved understanding of pathophysiology and implementation of advanced myelographic techniques. Here, we synthesize recent updates and contextualize them in an algorithm for diagnosis and treatment of SIH, highlighting basic principles and points of practice variability or continued debate. This discussion includes finer points of SIH diagnosis, CSF leak classification systems, less common types and variants of CSF leaks, brain MRI Bern scoring, potential SIH complications, key technical considerations, and positioning strategies for different types of dynamic myelography. The roles of conservative measures, non-targeted or targeted blood patches, surgery, and recently developed endovascular techniques are presented.

Objective assessment of patients with idiopathic normal pressure hydrocephalus following ventriculoperitoneal shunt placement using activity-monitoring data: pilot study.

OBJECTIVE: Idiopathic normal pressure hydrocephalus (iNPH) results in significant morbidity in the elderly with symptoms of dementia, gait instability, and urinary incontinence. In well-selected patients, ventriculoperitoneal shunt (VPS) placement often results in clinical improvement. Most postshunt assessments of patients rely on subjective scales. The goal of this study was to assess the utility of remote activity monitoring to provide objective evidence of gait improvement following VPS placement for iNPH. METHODS: Patients with iNPH were prospectively enrolled and fitted with 5 activity monitors (on the hip and bilateral thighs and ankles) that they wore for 4 days preoperatively within 30 days of surgery and for 4 days within 30 days postoperatively. Monitors collected continuous data for number of steps, cadence, body position (upright, prone, supine, and lateral decubitus), gait entropy, and the proportion of each day spent active or static. Data were retrieved from the devices and a comparison of pre- and postoperative movement assessment was performed. The gait data were also correlated with formal clinical gait assessments before and after lumbar puncture and with motion analysis laboratory testing at baseline and 1 month and 1 year after VPS placement. RESULTS: Twenty patients fulfilled the inclusion and exclusion criteria (median age 76 years). The baseline median number of daily steps was 1929, the median percentage of the day spent inactive was 70%, the median percentage of the day with a static posture was 95%, the median gait velocity was 0.49 m/sec, and the median number of steps required to turn was 8. There was objective improvement in median entropy from pre- to postoperatively, increasing from 0.6 to 0.8 (p = 0.002). There were no statistically significant differences for any of the remaining variables measured by the activity monitors when comparing the preoperative to the 1-month postoperative time point. All variables from motion analysis testing showed statistically significant differences or a trend toward significance at 1 year after VPS placement. Among the significantly correlated variables at baseline, cadence was inversely correlated with percentage of gait cycle spent in the support phase (contact with ground vs swing phase). CONCLUSIONS: This pilot study suggests that activity monitoring provides an early objective measure of improvement in gait entropy after VPS placement among patients with iNPH, although a more significant improvement was noted on the detailed clinical gait assessments. Further long-term studies are needed to determine the utility of remote monitoring for assessing gait improvement following VPS placement.

Features of Idiopathic Intracranial Hypertension on MRI With MR Elastography: Prospective Comparison With Control Individuals and Assessment of Postintervention Changes.

BACKGROUND. Understanding of dynamic changes of MRI findings in response to intracranial pressure (ICP) changes in idiopathic intracranial hypertension (IIH) is limited. Brain stiffness, as assessed by MR elastography (MRE), may reflect changes in ICP. OBJECTIVE. The purpose of this study was to compare pituitary height, ventricular size, and brain stiffness between patients with IIH and control individuals and to evaluate for changes in these findings in patients with IIH after interventions to reduce ICP. METHODS. This prospective study included 30 patients (28 women, two men; median age, 29.9 years) with IIH and papilledema and 21 control individuals (21 women, 0 men; median age, 29.1 years), recruited from January 2017 to July 2019. All participants underwent 3-T brain MRI with MRE; patients with IIH underwent additional MRI examinations with MRE after acute intervention (lumbar puncture with normal closing pressure; n = 11) and/or chronic intervention (medical management or venous sinus stenting with resolution or substantial reduction in papilledema; n = 12). Pituitary height was measured on sagittal MP-RAGE images. Ventricular volumes were estimated using unified segmentation, and postintervention changes were assessed by tensor-based morphometry. Stiffness pattern score and regional stiffness values were estimated from MRE. RESULTS. In patients with IIH, median pituitary height was smaller than in control individuals (3.1 vs 4.9 mm, p < .001) and was increased after chronic (4.0 mm, p = .05), but not acute (2.3 mm, p = .50), intervention. Ventricular volume was not different between patients with IIH and control individuals (p = .33) and did not change after acute (p = .83) or chronic (p = .97) intervention. In patients with IIH, median stiffness pattern score was greater than in control individuals (0.25 vs 0.15, p < .001) and decreased after chronic (0.23, p = .11) but not acute (0.25, p = .49) intervention. Median occipital lobe stiffness was 3.08 kPa in patients with IIH versus 2.94 kPa in control individuals (p = .07) and did not change after acute (3.24 kPa, p = .73) or chronic (3.10 kPa, p = .83) intervention. CONCLUSION. IIH is associated with a small pituitary and increased brain stiffness pattern score; both findings may respond to chronic interventions to lower ICP. CLINICAL IMPACT. The "partially empty sella" sign and brain stiffness pattern score may serve as dynamic markers of ICP in IIH.

Lateral decubitus dynamic CT myelography for fast cerebrospinal fluid leak localization.

Dynamic CT myelography is used to precisely localize fast spinal CSF leaks. The procedure is most commonly performed in the prone position, which successfully localizes most fast ventral leaks. We have recently encountered a small subset of patients in whom prone dynamic CT myelography is unsuccessful in localizing leaks. We sought to determine the added value of lateral decubitus dynamic CT myelography, which is occasionally attempted in our practice, in localizing the leak after failed prone dynamic CT myelography. We retrospectively identified 6 patients who underwent lateral decubitus dynamic CT myelography, which was performed in each case because their prone dynamic CT myelogram was unrevealing. Two neuroradiologists independently reviewed preprocedural spine MRI and all dynamic CT myelograms for each patient. Lateral decubitus positioning allowed for precise leak localization in all 6 patients. Five of six patients were noted to have dorsal and/or lateral epidural fluid collections on spine MRI. One patient had a single prominent diverticulum on spine MRI (larger than 6 mm), whereas the others had no prominent diverticula. Our study suggests that institutions performing dynamic CT myelography to localize fast leaks should consider a lateral decubitus study if performing the study in the prone position is unrevealing. Furthermore, the presence of dorsal and/or lateral epidural fluid collections on spine MRI may suggest that a lateral decubitus study is of higher yield and could be considered initially.

Population-Based Evaluation of Indirect Signs of Increased Intracranial Pressure.

BACKGROUND: The Mayo Clinic Study of Aging (MCSA) is a unique prospective study that systematically evaluates the normal aging population and includes many participants undergoing both MRI and lumbar puncture (LP). Using MCSA date, we aimed to determine the prevalence of indirect signs of raised intracranial pressure (ICP) on MRI and whether these correlate with LP opening pressure (OP). This is a large-scale study that evaluates how often indirect signs of increased ICP occur in a normal population. METHODS: MCSA participants who had an MRI within 3 months of an LP with recorded OP were included in the study. MRIs were reviewed for indirect signs of raised ICP, including pituitary to sella (P/S) ratio, cerebellar tonsillar ectopia, and optic nerve sheath diameter (ONSD). These signs were evaluated for correlations with OP and influences from body mass index (BMI) and obstructive sleep apnea (OSA). RESULTS: Five hundred ninety-seven MCSA patients were identified who underwent both LP and MRI. Two hundred sixty (43.6%) were women. The median age was 70.7 years (range 32.6-92.7). Median OP was 152 mm H2O (range 60-314 mm H2O), with 91 (15.2%) participants having an OP ≥ 200 mm H2O. Empty or partially empty sella was seen in 81 (12.8%) of the cohort. The P/S ratio decreased with increasing OP (r = -0.3, P < 0.001). There was a weak correlation between OP and average ONSD (r = 0.184, P = 0.01), which was no longer significant when accounting for age, gender, and BMI (partial r2 = 0.014, P = 0.097). There was no correlation between OP and cerebellar tonsillar ectopia. OSA was associated with increased ONSD (P = 0.004), but this did not remain statistically significant after accounting for age, gender, and BMI (P = 0.085). CONCLUSION: Smaller pituitary gland size correlated with increasing OP. This suggests that ICP is a continuum with some normal individuals demonstrating asymptomatic radiologic signs of raised ICP.

Autonomic dysfunction following COVID-19 infection: an early experience.

PURPOSE: Post-COVID-19 syndrome is a poorly understood aspect of the current pandemic, with clinical features that overlap with symptoms of autonomic/small fiber dysfunction. An early systematic analysis of autonomic dysfunction following COVID-19 is lacking and may provide initial insights into the spectrum of this condition. METHODS: We conducted a retrospective review of all patients with confirmed history of COVID-19 infection referred for autonomic testing for symptoms concerning for para-/postinfectious autonomic dysfunction at Mayo Clinic Rochester or Jacksonville between March 2020 and January 2021. RESULTS: We identified 27 patients fulfilling the search criteria. Symptoms developed between 0 and 122 days following the acute infection and included lightheadedness (93%), orthostatic headache (22%), syncope (11%), hyperhidrosis (11%), and burning pain (11%). Sudomotor function was abnormal in 36%, cardiovagal function in 27%, and cardiovascular adrenergic function in 7%. The most common clinical scenario was orthostatic symptoms without tachycardia or hypotension (41%); 22% of patients fulfilled the criteria for postural tachycardia syndrome (POTS), and 11% had borderline findings to support orthostatic intolerance. One patient each was diagnosed with autoimmune autonomic ganglionopathy, inappropriate sinus tachycardia, vasodepressor syncope, cough/vasovagal syncope, exacerbation of preexisting orthostatic hypotension, exacerbation of sensory and autonomic neuropathy, and exacerbation of small fiber neuropathy. CONCLUSION: Abnormalities on autonomic testing were seen in the majority of patients but were mild in most cases. The most common finding was orthostatic intolerance, often without objective hemodynamic abnormalities on testing. Unmasking/exacerbation of preexisting conditions was seen. The temporal association between infection and autonomic symptoms implies a causal relationship, which however cannot be proven by this study.

Variability of Consecutive Lumbar Puncture Opening Pressures.

BACKGROUND: Lumbar puncture (LP) opening pressures (OPs) are known to fluctuate based on diurnal, environmental, and pathologic conditions. Despite their dynamic nature, single OPs are often deemed sufficient for diagnosis of elevated intracranial pressures (ICPs) in nonspecialists' hands. The purpose of this study was to determine the variability of consecutive LP OPs at a large referral center to determine the potential range of variability for a given LP OP. METHODS: In this retrospective cohort study, medical records of all patients seen at Mayo Clinic, Rochester, MN, from January 1, 2001, through June 1, 2016, were screened for ≥2 LP OPs within 30 days of each other. Patients with pathologic conditions known to influence ICP were excluded. RESULTS: There were 148 eligible patients (39.2% female) with mean age of 63.5 ± 15.5 years and mean body mass index (BMI) 28.0 ± 6.0. The LPs were a mean of 10 ± 9 days apart. Mean OP for the first and second LP was 149 ± 51 mm H2O and 148 ± 48 mm H2O (P = 0.78), respectively, with a mean difference of 1 mm H2O, providing an overall coefficient of repeatability (CR) of 86.4 between consecutive LPs. There was a significant correlation between initial OP and BMI (r = 0.39, P < 0.001). OP >200 mm H2O had a significantly higher CR of 111.4, compared to OP <200 mm H2O, with CR 74.6 (P = 0.006). CRs were also higher for patients with diagnoses of headache (P = 0.002) or anxiety (P = 0.03). CONCLUSIONS: Higher initial LP OP, headache, and anxiety were associated with greater variability on subsequent LPs. OPs that are not consistent with the patients' clinical signs and symptoms should therefore be interpreted with caution.

Headache due to spontaneous spinal cerebrospinal fluid leak secondary to cerebrospinal fluid-venous fistula: Case series.

OBJECTIVE: Cerebrospinal fluid-venous fistula is an uncommon cause of spontaneous spinal cerebrospinal fluid leak (SSCSFL). We aim to describe the clinical presentation, imaging evaluation, treatment and outcome of SSCSFL secondary to cerebrospinal fluid-venous fistula. METHODS: A retrospective review was undertaken of SSCSFL cases secondary to cerebrospinal fluid-venous fistula confirmed radiologically or intraoperatively, seen at our institution from January 1994 to March 2019. Cases with undetermined SSCSFL etiology, alternative etiology or unconfirmed fistula were excluded. RESULTS: Forty-four of 156 patients met the inclusion criteria (31 women, 13 men). Mean age of symptom onset was 52.6 years (SD 8.7, range 33-71 years). Headache was the presenting symptom in almost all, typically daily (69%), and most often in occipital/suboccipital regions. Headache character was most commonly pressure (38%), followed by throbbing/pulsing (21.4%). Orthostatic headache worsening occurred in 69% and an even greater percentage of patients (88%) reported Valsalva-induced headache exacerbation or precipitation. Headache occurred in isolation to Valsalva maneuvers in 12%. Of 37 patients with documented cerebrospinal fluid opening pressure, 13% were <6 cmH2O; 84%, 7-20 cmH2O; and one, 25 cmH2O. Fistulas were almost exclusively thoracic (95.5%). Only one patient responded definitively to epidural blood patch (EBP). Forty-two patients underwent surgery. Most improved following surgery; 48.7% were completely headache free and 26.8% had at least 50% improvement. CONCLUSION: In our series, cerebrospinal fluid-venous fistula was associated with a greater occurrence of Valsalva-induced headache exacerbation or precipitation than orthostatic headache and did not respond to EBP. Surgery provided significant improvement. Cerebrospinal fluid-venous fistula should be considered early in the differential diagnosis of Valsalva-induced ("cough") headache.

Neuropathology of autonomic dysfunction in synucleinopathies.

The synucleinopathies-Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, and pure autonomic failure-result from distinct patterns of abnormal α-synuclein aggregation throughout the nervous system. Autonomic dysfunction in these disorders results from variable involvement of the central and peripheral autonomic networks. The major pathologic hallmark of Parkinson's disease and dementia with Lewy bodies is Lewy bodies and Lewy neurites; of multiple system atrophy, oligodendroglial cytoplasmic inclusions; and of pure autonomic failure, peripheral neuronal cytoplasmic inclusions. Clinical manifestations include orthostatic hypotension, thermoregulatory dysfunction, gastrointestinal dysmotility, and urogenital dysfunction with neurogenic bladder and sexual dysfunction. Strong evidence supports isolated idiopathic rapid eye movement sleep disorder as a significant risk factor for the eventual development of synucleinopathies with autonomic and/or motor involvement. In contrast, some neurologically normal elderly individuals have Lewy-related pathology. Future work may reveal protective or vulnerability factors that allow some patients to harbor Lewy pathology without overt autonomic dysfunction. © 2018 International Parkinson and Movement Disorder Society.

Orthostatic Headache After Suboccipital Craniectomy Without CSF Leak: Two Case Reports.

OBJECTIVE: To review the clinical and radiographic characteristics of orthostatic headache following suboccipital craniectomy without CSF leak after encountering 2 such patients. BACKGROUND: Orthostatic headache may occur without CSF leak, suggesting alternative mechanisms for postural head pain in some patients. METHODS: Patients who were referred for orthostatic headache and suspected CSF leak within 1 year after suboccipital craniectomy but who had negative post-operative head and spine MRI, normal radioisotope cisternography, and normal or elevated CSF opening pressure were identified and their medical records reviewed. RESULTS: Two patients satisfied all inclusion criteria. One underwent suboccipital craniectomy for treatment of Chiari malformation type I in adolescence; the same surgical approach was used to resect a posterior fossa meningioma in the second. Both patients had non-orthostatic headache before surgery and newly developed orthostatic headache later. Delay from surgery to orthostatic headache onset was variable (2-9 months). Headaches were predominantly occipital and pressure-like, worsened by upright posture, bending forward, and exertion. MRI consistently showed adequate decompression of the posterior fossa. Epidural blood patches were unhelpful in the one patient in whom they were performed. CONCLUSIONS: Orthostatic headaches may develop after suboccipital craniectomy in the absence of CSF leak. Possible mechanisms include (1) scarring of the dura in the posterior fossa that leads to compensatory increased distensibility of lumbar dura and (2) sensitization of mechanosensitive dural nociceptors from altered skull-dura apposition.

Endovascular Embolization Techniques for Cerebrospinal Fluid-Venous Fistula in the Treatment of Spontaneous Intracranial Hypotension.

Cerebrospinal fluid-venous fistula (CVF) is an important cause of spontaneous intracranial hypotension (SIH), a condition characterized by low cerebrospinal fluid (CSF) volume and orthostatic headaches. The pathogenesis of CVF is thought to be direct connection of the spinal dura to one or more veins in the epidural space, allowing unregulated flow of CSF into the venous system. Herein, we provide a comprehensive review of the endovascular management of CVF in patients with SIH. We also focus on the various techniques and devices used in endovascular treatment, as well as the pathogenesis, diagnosis, and alternative treatment options of CVF.

Ventriculoperitoneal Shunt Placement Safety in Idiopathic Normal Pressure Hydrocephalus: Anticoagulated Versus Non-Anticoagulated Patients.

BACKGROUND: Many patients with idiopathic normal pressure hydrocephalus (iNPH) have medical comorbidities requiring anticoagulation that could negatively impact outcomes. This study evaluated the safety of ventriculoperitoneal shunt placement in iNPH patients on systemic anticoagulation versus those not on anticoagulation. METHODS: Patients >60 years of age with iNPH who underwent shunting between 2018 and 2022 were retrospectively reviewed. Baseline demographics, comorbidities (quantified by modified frailty index and Charlson comorbidity index), anticoagulant/antiplatelet agent use (other than aspirin), operative details, and complications were collected. Outcomes of interest were the occurrence of postoperative hemorrhage and overdrainage. RESULTS: A total of 234 patients were included in the study (mean age 75.22 ± 6.04 years; 66.7% male); 36 were on anticoagulation/antiplatelet therapy (excluding aspirin). This included 6 on Warfarin, 19 on direct Xa inhibitors, 10 on Clopidogrel, and 1 on both Clopidogrel and Warfarin. Notably, 70% of patients (164/234) used aspirin alone or combined with anticoagulation or clopidogrel. Baseline modified frailty index was similar between groups, but those on anticoagulant/antiplatelet therapy had a higher mean Charlson comorbidity index (2.67 ± 1.87 vs. 1.75 ± 1.84; P = 0.001). Patients on anticoagulants were more likely to experience tract hemorrhage (11.1 vs. 2.5%; P = 0.03), with no significant difference in the rates of intraventricular hemorrhage or overdrainage-related subdural fluid collection. CONCLUSIONS: Anticoagulant and antiplatelet agents are common in the iNPH population, and patients on these agents experienced higher rates of tract hemorrhage following ventriculoperitoneal shunt placement; however, overall hemorrhagic complication rates were similar.

Benefits of Photon-Counting CT Myelography for Localization of Dural Tears in Spontaneous Intracranial Hypotension.

Photon-counting CT is an increasingly used technology with numerous advantages over conventional energy-integrating detector CT. These include superior spatial resolution, high temporal resolution, and inherent spectral imaging capabilities. Recently, photon-counting CT myelography was described as an effective technique for the detection of CSF-venous fistulas, a common cause of spontaneous intracranial hypotension. It is likely that photon-counting CT myelography will also have advantages for the localization of dural tears, a separate type of spontaneous spinal CSF leak that requires different myelographic techniques for accurate localization. To our knowledge, prior studies on photon-counting CT myelography have been limited to techniques for detecting CSF-venous fistulas. In this technical report, we describe our technique and early experience with photon-counting CT myelography for the localization of dural tears.

Diagnosis and Treatment of Spontaneous Intracranial Hypotension: Role of Epidural Blood Patching.

Purpose of Review: This review focuses on the challenges of diagnosing and treating spontaneous intracranial hypotension (SIH), a condition caused by spinal CSF leakage. It emphasizes the need for increased awareness and advocates for early and thoughtful use of empirical epidural blood patches (EBPs) in suspected cases. Recent Findings: SIH diagnosis is hindered by variable symptoms and inconsistent imaging results, including normal brain MRI and unreliable spinal opening pressures. It is crucial to consider SIH in differential diagnoses, especially in patients with connective tissue disorders. Early EBP intervention is shown to improve outcomes. Summary: SIH remains underdiagnosed and undertreated, requiring heightened awareness and understanding. This review promotes proactive EBP use in managing suspected SIH and calls for continued research to advance diagnostic and treatment methods, emphasizing the need for innovative imaging techniques for accurate diagnosis and timely intervention.

Natural history of spontaneous intracranial hypotension: a clinical and imaging study.

BACKGROUND: Although spontaneous intracranial hypotension (SIH) is well studied, there are few studies of the clinical and imaging history of SIH without interventional treatments. For example, what is the natural history of those who are untreated or treated only with conservative measures? OBJECTIVE: To conduct a retrospective study examining changes in imaging findings for patients with SIH without interventional treatments and to study associations between imaging findings and clinical symptoms. METHODS: Included patients had a clinical diagnosis of SIH, were seen at Mayo Clinic between 1999 and 2021, had a brain MRI scan indicating SIH (Bern score), and had a brain MRI scan 6 or more months later without intervening leak-related interventional treatment. Bern scores were assigned for the first and last MRI scans prior to treatment. Patients were also grouped into three qualitative categories: overall improvement of symptoms, stable symptoms, or worsened symptoms based on patient report during the clinical visit at the time of the follow-up brain MRI scan. RESULTS: Among 46 patients with untreated SIH, the Bern score improved over time in 11 (24%), was stable in 30 (65%), and worsened in 5 (11%). Two patients (4.3%) showed complete resolution of all abnormalities by the Bern scoring criteria. Symptoms improved in 7 (15%), were stable in 29 (63%), and worsened in 10 (22%). CONCLUSIONS: In patients with brain MRI evidence of SIH, almost 25% demonstrated radiographic improvement, and 15% reported clinical improvement, during at least 6 months of observation or conservative treatment. Most had stable, persistent MRI abnormalities and symptoms when SIH was untreated.