Prehospital stroke management and mobile stroke units.

PURPOSE OF REVIEW: Delayed presentation at the hospital contributes to poorer patient outcomes and undertreatment of acute stroke patients. This review will discuss recent developments in prehospital stroke management and mobile stroke units aimed to improve timely access to treatment within the past 2 years and will point towards future directions. RECENT FINDINGS: Recent progress in research into prehospital stroke management and mobile stroke units ranges from interventions aimed at improving patients' help-seeking behaviour, to the education of emergency medical services team members, to the use of innovative referral methods, such as diagnostic scales, and finally to evidence of improved outcomes by the use of mobile stroke units. SUMMARY: Understanding is increasing about the need for optimizing stroke management over the entire stroke rescue chain with the goal of improving access to highly effective time-sensitive treatment. In the future, we can expect that novel digital technologies and artificial intelligence will become relevant in effective interaction between prehospital and in-hospital stroke-treating teams, with beneficial effects on patients' outcomes.

Impact of mobile stroke units.

Since its first introduction in clinical practice in 2008, the concept of mobile stroke unit enabling prehospital stroke treatment has rapidly expanded worldwide. This review summarises current knowledge in this young field of stroke research, discussing topics such as benefits in reduction of delay before treatment, vascular imaging-based triage of patients with large-vessel occlusion in the field, differential blood pressure management or prehospital antagonisation of anticoagulants. However, before mobile stroke units can become routine, several questions remain to be answered. Current research, therefore, focuses on safety, long-term medical benefit, best setting and cost-efficiency as crucial determinants for the sustainability of this novel strategy of acute stroke management.

Effects of a Feedback-Demanding Stroke Clock on Acute Stroke Management: A Randomized Study.

BACKGROUND AND PURPOSE: This randomized study aimed to evaluate whether the use of a stroke clock demanding active feedback from the stroke physician accelerates acute stroke management. METHODS: For this randomized controlled study, a large-display alarm clock was installed in the computed tomography room, where admission, diagnostic work-up, and intravenous thrombolysis occurred. Alarms were set at the following target times after admission: (1) 15 minutes (neurological examination completed); (2) 25 minutes (computed tomography scanning and international normalized ratio determination by point-of-care laboratory completed); and (3) 30 minutes (intravenous thrombolysis started). The responsible stroke physician had to actively provide feedback by pressing a buzzer button. The alarm could be avoided by pressing the button before time out. Times to therapy decision (primary end point, defined as the end of all diagnostic work-up required for decision for or against recanalizing treatment), neurological examination, imaging, point-of-care laboratory, needle, and groin puncture were assessed by a neutral observer. Functional outcome (modified Rankin Scale) was assessed at day 90. RESULTS: Of 107 participants, 51 stroke clock patients exhibited better stroke-management metrics than 56 control patients. Times from door to (1) end of all indicated diagnostic work-up (treatment decision time; 16.73 versus 26.00 minutes, P<0.001), (2) end of neurological examination (7.28 versus 10.00 minutes, P<0.001), (3) end of computed tomography (11.17 versus 14.00 minutes, P=0.002), (4) end of computed tomography angiography (14.00 versus 17.17 minutes, P=0.001), (5) end of point-of-care laboratory testing (12.14 versus 20.00 minutes, P<0.001), and (6) needle times (18.83 versus 47.00 minutes, P=0.016) were improved. In contrast, door-to-groin puncture times and functional outcomes at day 90 were not significantly different. CONCLUSIONS: This study showed that the use of a stroke clock demanding active feedback significantly improves acute stroke-management metrics and, thus, represents a potential low-cost strategy for streamlining time-sensitive stroke treatment.

Mobile Stroke Unit in the UK Healthcare System: Avoidance of Unnecessary Accident and Emergency Admissions.

BACKGROUND: Acute stroke patients are usually transported to the nearest hospital regardless of their required level of care. This can lead to increased pressure on emergency departments and treatment delay. OBJECTIVE: The aim of the study was to explore the benefit of a mobile stroke unit (MSU) in the UK National Health Service (NHS) for reduction of hospital admissions. METHODS: Prospective cohort audit observation with dispatch of the MSU in the East of England Ambulance Service area in Southend-on-Sea was conducted. Emergency patients categorized as code stroke and headache were included from June 5, 2018, to December 18, 2018. Rate of avoided admission to the accident and emergency (A&E) department, rate of admission directly to target ward, and stroke management metrics were assessed. RESULTS: In 116 MSU-treated patients, the following diagnoses were made: acute stroke, n = 33 (28.4%); transient ischaemic attacks, n = 13 (11.2%); stroke mimics, n = 32 (27.6%); and other conditions, n = 38 (32.8%). Pre-hospital thrombolysis was administered to 8 of 28 (28.6%) ischaemic stroke patients. Pre-hospital diagnosis avoided hospital admission for 29 (25.0%) patients. As hospital treatment was indicated, 35 (30.2%) patients were directly triaged to the stroke unit, 1 patient (0.9%) even directly to the catheter laboratory. Thus, only 50 (43.1%) patients required transfer to the A&E department. Moreover, the MSU enabled thrombolysis with a median dispatch-to-needle time of 42 min (interquartile range, 40-60). CONCLUSION: This first deployment of an MSU in the UK NHS demonstrated improved triage decision-making for or against hospital admission and admission to the appropriate target ward, thereby reducing pressure on strained A&E departments.

B-Mode Transorbital Ultrasonography for the Diagnosis of Idiopathic Intracranial Hypertension: A Systematic Review and Meta-Analysis.

In patients with idiopathic intracranial hypertension (IIH), transorbital sonography (TOS) may reveal an enlargement of the optic nerve sheath diameter (ONSD) and the presence of optic disc elevation (ODE), as a sign of an increase in intracranial pressure (ICP). We systematically reviewed the TOS findings in adults with IIH. MEDLINE, EMBASE, Cochrane Library and CENTRAL (1966 - May 2017) were searched to identify studies reporting data on patients with IIH assessed by B mode-TOS. Data were extracted and included in a meta-analysis, and the quality of the included studies was evaluated. 5 studies with 96 patients were included. The values of ODE were 0.8 - 1.2 mm and ONSD was 6.2 - 6.76 mm in IIH patients vs. 4.3 - 5.7 mm in controls. In IIH patients the ONSD was significantly higher compared to controls (overall weighted mean difference of 1.3 mm (95 % CI: 0.6 - 1.9 mm)). The meta-analysis of proportion of papilledema based on results of three studies revealed a pooled estimator of 87 % (95 % CI: 76 - 94 %). IIH patients have higher ONSD values and higher frequency of ODE compared to controls. The indirect, noninvasive ICP assessment using TOS may be useful in supporting the clinical diagnosis of IIH in adults by detecting increased ONSD values and the presence of ODE.

Mobile Stroke Units - Cost-Effective or Just an Expensive Hype?

PURPOSE OF REVIEW: Acute stroke is a treatable disease. Nevertheless, only a minority of patients obtain guideline-adjusted therapy. One major reason is the small time window in which therapies have to be administered in order to reverse or mitigate brain injury and prevent disability. The Mobile Stroke Unit (MSU) concept, available for a decade now, is spreading worldwide, comprising ambulances, fully equipped with computed tomography, laboratory unit and telemedicine connection to the stroke centre and staffed with a specialised stroke team. Besides its benefits, this concept adds a relevant amount of costs to health services. RECENT FINDINGS: The feasibility of the MSU and its impact on reducing treatment times have been proven by several research trials. In addition, pre-hospital stroke diagnosis including computed tomographic angiography analysis facilitates correct triage of patients, needing mechanical recanalization, thereby reducing the number of secondary or inter-hospital transfers. Even so, the concept is not yet fully implemented on a broad scale. One reason is the still open question of cost-effectiveness. There are assumptions based on the randomised trials of MSUs hinting towards an acceptable amount of money per quality-adjusted life years and overall cost-effectiveness. Up to now, neither a prospective analysis nor a consideration of secondary transfer avoidance is available. The MSU concept is an innovative and impactful strategy to improve stroke management, especially in times of constraints in healthcare economics and health care professionals. Prospective information is needed to answer the cost-effectiveness question satisfactorily.

Prehospital Computed Tomography Angiography in Acute Stroke Management.

BACKGROUND: An ambulance equipped with a computed tomography (CT) scanner, a point-of-care laboratory, and telemedicine capabilities (mobile stroke unit [MSU]) has been shown to enable the delivery of thrombolysis to stroke patients directly at the emergency site, thereby significantly decreasing time to treatment. However, work-up in an MSU that includes CT angiography (CTA) may also potentially facilitate triage of patients directly to the appropriate target hospital and specialized treatment, according to their individual vascular pathology. METHODS: Our institution manages a program investigating the prehospital management of patients with suspicion of acute stroke. Here, we report a range of scenarios in which prehospital CTA could be relevant in triaging patients to the appropriate target hospital and to the individually required treatment. RESULTS: Prehospital CTA by use of an MSU allowed to detect large vessel occlusion of the middle cerebral artery in one patient with ischemic stroke and occlusion of the basilar artery in another, thereby allowing rational triage to comprehensive stroke centers for immediate intra-arterial treatment. In complementary cases, prehospital imaging not only allowed diagnosis of parenchymal hemorrhage with a spot sign indicating ongoing bleeding in one patient and of subarachnoid hemorrhage in another but also clarified the underlying vascular pathology, which was relevant for subsequent triage decisions. CONCLUSION: Defining the vascular pathology by CTA directly at the emergency site may be beneficial in triaging patients with various cerebrovascular diseases to the most appropriate target hospital and specialized treatment.

First Automated Stroke Imaging Evaluation via Electronic Alberta Stroke Program Early CT Score in a Mobile Stroke Unit.

BACKGROUND: Recently, a mobile stroke unit (MSU) was shown to facilitate acute stroke treatment directly at the emergency site. The neuroradiological expertise of the MSU is improved by its ability to detect early ischemic damage via automatic electronic (e) evaluation of CT scans using a novel software program that calculates the electronic Alberta Stroke Program Early CT Score (e-ASPECTS). METHODS: The feasibility of integrating e-ASPECTS into an ambulance was examined, and the clinical integration and utility of the software in 15 consecutive cases evaluated. RESULTS: Implementation of e-ASPECTS onto the MSU and into the prehospital stroke management was feasible. The values of e-ASPECTS matched with the results of conventional neuroradiologic analysis by the MSU team. The potential benefits of e-ASPECTS were illustrated by three cases. In case 1, excluding early infarct signs supported the decision to directly perform prehospital thrombolysis. In case 2, in which stroke was caused by large-vessel occlusion, the high e-ASPECTS value supported the decision to initiate intra-arterial treatment and triage the patient to a comprehensive stroke center. In case 3, the e-ASPECTS value was 10, indicating the absence of early infarct signs despite pre-existing cerebral microangiopathy and macroangiopathy, a finding indicating the program's robustness against artefacts. CONCLUSIONS: This study on the integration of e-ASPECTS into the prehospital stroke management via a MSU showed for the first time that such integration is feasible, and aids both decision regarding the treatment option and the triage regarding the most appropriate target hospital.

Retrospective Consent to Hemicraniectomy after Malignant Stroke among the Elderly, Despite Impaired Functional Outcome.

BACKGROUND: Decompressive hemicraniectomy (DHC) after space-occupying strokes among patients older than 60 years has been shown to reduce mortality rates but at the cost of severe disability. There is an ongoing debate about what could be considered an acceptable outcome for these patients. Data about retrospective consent to the procedure after lengthy time periods are lacking. METHODS: This study included 79 consecutive patients who underwent DHC during a 7.75-year period. Surviving patients were assessed for functional and psychological outcome, quality of life (QoL) and retrospective consent for the procedure. Patients younger than 60 years were compared with older patients. RESULTS: Of our 79 patients, 44 were younger than 60 years (median 50 years, interquartile range (IQR) 19-59 years) and 35 were older (median 68 years, interquartile range 60-87 years). The 30-day mortality rate was higher for the older group, but the difference was not statistically significant. Functional outcome was significantly better in the younger group: 31% of the patients in this group vs. 10% in the older group had a modified Rankin Scale score of 0-3 (p = 0.046). The mean National Institutes of Health Stroke Scale score was 17 ± 14 for the younger group and 29 ± 15 for the older group (p = 0.002). On the 36-Item Short Form Health Survey, with the exception of the item 'General health', the older group reported higher values for all items, with statistically significant differences between the 2 groups on the items 'Role limitation emotional' (p = 0.0007) and 'Vitality' (p = 0.02). In the younger group, 29% of patients retrospectively declined consent for DHC opposed to 0% of patients in the older group (p = 0.07). CONCLUSIONS: Despite impaired functional outcome after DHC, indicators of QoL and retrospective consent are higher for patients older than 60 years over the long term. This finding should be taken into account by those who counsel patients and caregivers with regard to this serious procedure.

'Stroke Room': Diagnosis and Treatment at a Single Location for Rapid Intraarterial Stroke Treatment.

BACKGROUND: For patients with acute ischemic stroke, intra-arterial treatment (IAT) is considered to be an effective strategy for removing the obstructing clot. Because outcome crucially depends on time to treatment ('time-is-brain' concept), we assessed the effects of an intervention based on performing all the time-sensitive diagnostic and therapeutic procedures at a single location on the delay before intra-arterial stroke treatment. METHODS: Consecutive acute stroke patients with large vessel occlusion who obtained IAT were evaluated before and after implementation (April 26, 2010) of an intervention focused on performing all the diagnostic and therapeutic measures at a single site ('stroke room'). RESULT: After implementation of the intervention, the median intervals between admission and first angiography series were significantly shorter for 174 intervention patients (102 min, interquartile range (IQR) 85-120 min) than for 81 control patients (117 min, IQR 89-150 min; p < 0.05), as were the intervals between admission and clot removal or end of angiography (152 min, IQR 123-185 min vs. 190 min, IQR 163-227 min; p < 0.001). However, no significant differences in clinical outcome were observed. CONCLUSION: This study shows for the, to our knowledge, first time that for patients with acute ischemic stroke, stroke diagnosis and treatment at a single location ('stroke room') saves crucial time until IAT.

Is prehospital treatment of acute stroke too expensive? An economic evaluation based on the first trial.

BACKGROUND: Recently, a strategy for treating stroke directly at the emergency site was developed. It was based on the use of an ambulance equipped with a scanner, a point-of-care laboratory, and telemedicine capabilities (Mobile Stroke Unit). Despite demonstrating a marked reduction in the delay to thrombolysis, this strategy is criticized because of potentially unacceptable costs. METHODS: We related the incremental direct costs of prehospital stroke treatment based on data of the first trial on this concept to one year direct cost savings taken from published research results. Key parameters were configuration of emergency medical service personnel, operating distance, and population density. Model parameters were varied to cover 5 different relevant emergency medical service scenarios. Additionally, the effects of operating distance and population density on benefit-cost ratios were analyzed. RESULTS: Benefits of the concept of prehospital stroke treatment outweighed its costs with a benefit-cost ratio of 1.96 in the baseline experimental setting. The benefit-cost ratio markedly increased with the reduction of the staff and with higher population density. Maximum benefit-cost ratios between 2.16 and 6.85 were identified at optimum operating distances in a range between 43.01 and 64.88 km (26.88 and 40.55 miles). Our model implies that in different scenarios the Mobile Stroke Unit strategy is cost-efficient starting from an operating distance of 15.98 km (9.99 miles) or from a population density of 79 inhabitants per km2 (202 inhabitants per square mile). CONCLUSION: This study indicates that based on a one-year benefit-cost analysis that prehospital treatment of acute stroke is highly cost-effective across a wide range of possible scenarios. It is the highest when the staff size of the Mobile Stroke Unit can be reduced, for example, by the use of telemedical support from hospital experts. Although efficiency is positively related to population density, benefit-cost ratios can be greater than 1 even in rural settings.

Perceived performance of activities of daily living by stroke patients: key in decision to call EMS and outcomes.

Background: Until recently, public education campaigns aimed at improving help-seeking behavior by acute stroke patients have achieved only limited or even no effects. Better understanding of psychological factors determining help-seeking behavior may be relevant in the design of more effective future campaigns. Methods: In this prospective, cross-sectional study, we interviewed 669 acute stroke patients within 72 h after hospital admission. The primary endpoint was the effect of psychological factors on the decision to call emergency medical services (EMS). Secondary endpoints were the effects of such factors on treatment rates and clinical improvement (difference between modified Rankin scale (MRS) scores at admission and at discharge). Results: Only 48.7% of the study population called the EMS. Multivariate logistic and linear regression analyses revealed that perception of unimpaired performance of activities of daily living (ADL) was the only psychological factor that predicted EMS use and outcomes. Thus, patients who perceived only minor impairment in performing ADL were less likely to use EMS (odds ratio, 0.54 [95% confidence interval, 0.38-0.76]; p = 0.001), had lower treatment rates, and had less improvement in MRS scores (b = 0.40, p = 0.004). Additional serial mediation analyses involving ischemic stroke patients showed that perception of low impairment in ADL decreased the likelihood of EMS notification, thereby increasing prehospital delays, leading to reduced thrombolysis rates and, finally, to reduced clinical improvement. Conclusion: Perception of unimpaired performance of ADL is a crucial barrier to appropriate help-seeking behavior after acute stroke, leading to undertreatment and less improvement in clinical symptoms. Thus, beyond improving the public's knowledge of stroke symptoms, future public education campaigns should focus on the need for calling the EMS in case of stroke symptoms even if daily activities do not seem to be severely impaired.

Point-of-care laboratory halves door-to-therapy-decision time in acute stroke.

Currently, stroke laboratory examinations are usually performed in the centralized hospital laboratory, but often planned thrombolysis is given before all results are available, to minimize delay. In this study, we examined the feasibility of gaining valuable time by transferring the complete stroke laboratory workup required by stroke guidelines to a point-of-care laboratory system, that is, placed at a stroke treatment room contiguous to the computed tomography, where the patients are admitted and where they obtain neurological, laboratory, and imaging examinations and treatment by the same dedicated team. Our results showed that reconfiguration of the entire stroke laboratory analysis to a point-of-care system was feasible for 200 consecutively admitted patients. This strategy reduced the door-to-therapy-decision times from 84 ± 26 to 40 ± 24 min (p < 0.001). Results of most laboratory tests (except activated partial thromboplastin time and international normalized ratio) revealed close agreement with results from a standard centralized hospital laboratory. These findings may offer a new solution for the integration of laboratory workup into routine hyperacute stroke management.

Reorganizing stroke and neurological intensive care during the COVID-19 pandemic in Germany.

The outbreak of coronavirus disease 19 (COVID-19) has dramatically imposed healthcare systems to reorganize their departments, including neurological wards. We aimed to describe the rearrangements made by stroke units (SU) and neurological intensive care units (ICU) in several German community and university hospitals facing the pandemic. This cross-sectional, survey-based, nationwide study collected data of 15 university and 4 community hospitals in Germany, being part of IGNITE Study Group, from April 1 to April 6, 2020. The rearrangements and implementation of safety measures in SUs, intermediate care units (IMC), and neurological ICUs were compared. 84.2% of hospitals implemented a separated area for patients awaiting their COVID-19 test results and 94.7% had a dedicated zone for their management. Outpatient treatment was reduced in 63.2% and even suspended in 36.8% of the hospitals. A global reduction of bed capacity was observed. Hospitals reported compromised stroke treatment (52.6%) and reduction of thrombolysis and thrombectomy rates (36.8%). All hospitals proposed special training for COVID-19 management, recurrent meetings and all undertook measures improving safety for healthcare workers. In an unprecedented global healthcare crisis, knowledge of the initial reorganization and response of German hospitals to COVID-19 may help finding effective strategies to face the ongoing pandemic.

Effects of state-wide implementation of the Los Angeles Motor Scale for triage of stroke patients in clinical practice.

BACKGROUND: The prehospital identification of stroke patients with large-vessel occlusion (LVO), that should be immediately transported to a thrombectomy capable centre is an unsolved problem. Our aim was to determine whether implementation of a state-wide standard operating procedure (SOP) using the Los Angeles Motor Scale (LAMS) is feasible and enables correct triage of stroke patients to hospitals offering (comprehensive stroke centres, CSCs) or not offering (primary stroke centres, PSCs) thrombectomy. METHODS: Prospective study involving all patients with suspected acute stroke treated in a 4-month period in a state-wide network of all stroke-treating hospitals (eight PSCs and two CSCs). Primary endpoint was accuracy of the triage SOP in correctly transferring patients to CSCs or PSCs. Additional endpoints included the number of secondary transfers, the accuracy of the LAMS for detection of LVO, apart from stroke management metrics. RESULTS: In 1123 patients, use of a triage SOP based on the LAMS allowed triage decisions according to LVO status with a sensitivity of 69.2% (95% confidence interval (95%-CI): 59.0-79.5%) and a specificity of 84.9% (95%-CI: 82.6-87.3%). This was more favourable than the conventional approach of transferring every patient to the nearest stroke-treating hospital, as determined by geocoding for each patient (sensitivity, 17.9% (95%-CI: 9.4-26.5%); specificity, 100% (95%-CI: 100-100%)). Secondary transfers were required for 14 of the 78 (17.9%) LVO patients. Regarding the score itself, LAMS detected LVO with a sensitivity of 67.5% (95%-CI: 57.1-78.0%) and a specificity of 83.5% (95%-CI: 81.0-86.0%). CONCLUSIONS: State-wide implementation of a triage SOP requesting use of the LAMS tool is feasible and improves triage decision-making in acute stroke regarding the most appropriate target hospital.

Prehospital stroke management in the thrombectomy era.

Acute stroke management has been revolutionised by evidence of the effectiveness of thrombectomy. Because time is brain in stroke care, the speed with which a patient with large vessel occlusion is transferred to a thrombectomy-capable centre determines outcome. Therefore, each link in the stroke rescue chain, starting with symptom onset and ending with recanalisation, should be streamlined. However, in contrast to inhospital delays, prehospital delays are unchanged despite substantial efforts in quality improvement. Furthermore, thrombectomy is offered by only a few, usually distant, specialised centres and not by the many other, usually nearer, hospitals. To take maximum advantage of the first so-called golden hours after stroke, and because of the difficulty of on-scene triage decision making with respect to the target hospital offering the required level of care, the focus of stroke research has shifted to the prehospital setting. Current research focuses on the effects of public education, implementation of protocols for emergency medical services for streamlining clinical investigations and accurate triage, use of preclinical scales for stroke recognition, and deployment of novel technical solutions such as smartphone applications, telemedicine, and mobile stroke units.

Sonography of optic nerve sheath diameter identifies patients with middle cerebral artery infarction at risk of a malignant course: a pilot prospective observational study.

INTRODUCTION: To assess the value of optic nerve sheath diameter (ONSD) measurements at different time points to predict the malignant evolution in middle cerebral artery (MCA) infarction and to investigate the relationship between ONSD and infarct volume on follow-up computed tomography (CT). METHODS: In a single-center prospective observational study, we recruited patients with MCA infarction and age- and sex-matched controls. Clinical characteristics including NationaI Institutes of Health Stroke Scale (NIHSS) and ONSD measurement were assessed during the first five days after symptom onset. Volumetric analysis of the infarction was performed by a neuroradiologist, who was blinded to results of ONSD measurement and clinical examinations, based on  CT scans. RESULTS: We enrolled 29 patients with MCA infarction, including 10 with malignant MCA (mMCA) infarction and 14 controls. Mean ONSD on admission was already larger in patients who had developed an mMCA (5.99 ± 0.32 mm) compared to patients with MCA infarction (4.98 ± 0.53 mm; P = 0.003), and to control patients (4.57 ± 0.29 mm; P < 0.001). Correlation was observed between the ONSD mean value bilateral measures per individual and volumetric evaluation of cerebral infarction in the CT scan after one day (r = 0.623; P = 0.002). An ONSD value of 5.6 mm predicted an mMCA with a sensitivity of 100% and specificity of 90% yielding a positive predictive value of 83% and negative predictive value of 100%. CONCLUSIONS: ONSD measurement might be accurate for the noninvasive detection of increased ICP and for the recognition of patients being likely to develop mMCA.

Normal brain aging and Alzheimer's disease are associated with lower cerebral pH: an in vivo histidine 1H-MR spectroscopy study.

It is unclear whether alterations in cerebral pH underlie Alzheimer's disease (AD) and other dementias. We performed proton spectroscopy after oral administration of histidine in healthy young and elderly persons and in patients with mild cognitive impairment and dementia (total N = 147). We measured cerebral tissue pH and ratios of common brain metabolites in relation to phosphocreatine and creatine (Cr) in spectra acquired from the hippocampus, the white matter (WM) of the centrum semiovale, and the cerebellum. Hippocampal pH was inversely associated with age in healthy participants but did not differ between patients and controls. WM pH was low in AD and, to a lesser extent, mild cognitive impairment but not in frontotemporal dementia spectrum disorders and pure vascular dementia. Furthermore, WM pH provided incremental diagnostic value in addition to N-acetylaspartate to Cr ratio. Our study suggests that in vivo assessment of pH may be a useful marker for the differentiation between AD and other types of dementia.