Quantitative Analysis of Retinal Perfusion in Patients with Frontotemporal Dementia Using Optical Coherence Tomography Angiography.

BACKGROUND: Optical coherence tomography angiography (OCT-A) provides detailed visualization of the perfusion of the vascular network of the eye. While in other forms of dementia, such as Alzheimer's disease and mild cognitive impairment, reduced retinal perfusion was frequently reported, data of patients with frontotemporal dementia (FTD) are lacking. OBJECTIVE: Retinal and optic nerve head perfusion was evaluated in patients with FTD with OCT-A. Quantitative OCT-A metrics were analyzed and correlated with clinical markers and vascular cerebral lesions in FTD patients. METHODS: OCT-A was performed in 18 eyes of 18 patients with FTD and 18 eyes of 18 healthy participants using RTVue XR Avanti with AngioVue. In addition, patients underwent a detailed ophthalmological, neurological, and neuropsychological examination, cerebral magnetic resonance imaging (MRI), and lumbar puncture. RESULTS: The flow density in the optic nerve head (ONH) and in the superficial capillary plexus (SCP) of the macula of patients was significantly lower compared to that of healthy controls (p < 0.001). Similarly, the VD in the deep capillary plexus (DCP) of the macula of patients was significantly lower compared to that of healthy controls (p < 0.001). There was no significant correlation between the flow density data, white matter lesions in brain MRI, cognitive deficits, and cerebrospinal fluid markers of dementia. CONCLUSIONS: Patients with FTD showed a reduced flow density in the ONH, and in the superficial and deep retinal capillary plexus of the macula, when compared with that of healthy controls. Quantitative analyses of retinal perfusion using OCT-A may therefore help in the diagnosis and monitoring of FTD. Larger and longitudinal studies are necessary to evaluate if OCT-A is a suitable biomarker for patients with FTD.

[Dementia with Lewy bodies: old and new knowledge-Part 2: treatment]. / Demenz mit Lewy-Körpern: alte und neue Erkenntnisse ­ Teil 2: Behandlung.

BACKGROUND: The treatment of patients with dementia with Lewy bodies (DLB) is multifaceted, as motor symptoms, cognitive symptoms, behavioral and psychological symptoms can occur in different constellations. In addition, the use of certain medications is limited (e.g., neuroleptics). OBJECTIVE: To summarize the main recent findings on the treatment of DLB. RESULTS: To date, there is no approved therapeutic option for the treatment of patients with DLB in Germany; moreover, the evidence base for pharmacological and non-pharmacological treatment is sparse. The currently consented treatment options are based on the treatment of motor symptoms in the same way as the treatment of Parkinson's disease and for behavioral symptoms based on the treatment for Alzheimer's disease. DISCUSSION: The treatment of DLB with its various symptoms is difficult and often can only be adequately achieved for the patient in close cooperation with a specialist.

[Dementia with Lewy bodies: old and new knowledge - Part 1: clinical aspects and diagnostics]. / Demenz mit Lewy-Körpern: alte und neue Erkenntnisse ­ Teil 1: Klinik und Diagnostik.

BACKGROUND: Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia after Alzheimer's disease. Patients with DLB often have a poor prognosis, with worse outcomes than patients with Alzheimer's disease in terms of important parameters, such as quality of life, caregiver burden, health-related costs, frequency of hospital and nursing home admissions, shorter time to severe dementia, and lower survival. The DLB is frequently misdiagnosed and often undertreated. Therefore, it is critical to diagnose DLB as early as possible to ensure optimal care and treatment. OBJECTIVE: The aim of this review article is to summarize the main recent findings on diagnostic tools, epidemiology and genetics of DLB. RESULTS: Precise clinical diagnostic criteria exist for DLB that enable an etiologic assignment. Imaging techniques are used as standard in DLB, especially also to exclude non-neurodegenerative causes. In particular, procedures in nuclear medicine have a high diagnostic value. DISCUSSION: The diagnosis is primarily based on clinical symptoms, although the development of in vivo neuroimaging and biomarkers is changing the scope of clinical diagnosis as well as research into this devastating disease.

Impact of enzyme replacement therapy and migalastat on left atrial strain and cardiomyopathy in patients with Fabry disease.

Aims: Cardiomyopathy in Fabry disease (FD) is a major determinant of morbidity and mortality. This study investigates the effects of FD-specific treatment using enzyme replacement therapy (ERT) and chaperone therapy on left atrial (LA) function using two-dimensional speckle tracking echocardiography (2DSTE). Methods and results: In this prospective observational single-center study, 20 FD patients [10 (50%) females] treated with migalastat, 48 FD patients [24 (50%) females] treated with ERT (agalsidase-alfa and agalsidase-beta), and 30 untreated FD patients (all females) as controls were analyzed. The mean follow-up time ranged from 26 to 81 months. 2DSTE was performed for left ventricle strain, right ventricle strain, and LA strain (LAS). FD-specific treated patients presented with increased left ventricular mass index (LVMi) and higher frequency of left ventricular hypertrophy at baseline, whereas untreated control patients showed normal baseline values. FD-specific treated (including migalastat and ERT) patients showed stabilization of LAS over time (p > 0.05). LVMi was also stable in treated FD patients during observation (p > 0.05). Conclusion: In patients with FD, treated with either ERT or chaperone therapy, LAS values measured by echocardiographic speckle tracking were stable over time, pointing toward disease stabilization.

Comparing two relaxation procedures to ease fatigue in multiple sclerosis: a single-blind randomized controlled trial.

BACKGROUND: Various relaxation procedures have been proposed to reduce fatigue in multiple sclerosis (MS). However, it is unknown, which type of relaxation has the largest effect on fatigue reduction and on autonomic nervous system (ANS) activity. OBJECTIVE: We aimed to compare two biofeedback-supported relaxation exercises: a deep breathing (DB) exercise and progressive muscle relaxation (PMR), which may ameliorate MS fatigue and alter ANS activity. METHODS: We performed a single-blind randomized clinical trial, introducing MS patients (n = 34) to the DB or PMR exercise. We first tested cardiovagal integrity, reflected by changes in heart rate variability (HRV) in response to DB. Participants then performed a fatigue-inducing vigilance task, followed by the DB or PMR. State fatigue was recorded consecutively at baseline, after the vigilance task, and after the relaxation exercise, along with HRV reflecting ANS activity. RESULTS: Only patients assigned to the PMR group experienced a significant drop in fatigue, whereas both relaxation exercises changed ANS activity. MS patients showed the expected autonomic response during the cardiovagal reflex test. The vigilance task elevated short-term feelings of fatigue and significantly reduced HRV parameters of parasympathetic activity. Trait fatigue was negatively correlated with HRV during the second half of the vigilance task. CONCLUSION: PMR alleviates short-term feelings of fatigue in persons with MS. The vigilance task in combination with HRV measurements may be helpful for evaluating relaxation procedures as a treatment of fatigue. Hereby, future studies should ensure longer and more frequent relaxation exercises and focus on patients with weak to moderate fatigue. TRIAL REGISTRATION: Trial Registry: DRKS00024358.

Ginkgo biloba Extract EGb 761 in the Treatment of Patients with Mild Neurocognitive Impairment: A Systematic Review.

Background: Many clinical trials testing Ginkgo biloba extract EGb 761 in patients with mild forms of cognitive impairment were conducted before widely accepted terms and diagnostic criteria for such conditions were available. This makes it difficult to compare any results from earlier and more recent trials. The objective of this systematic review was to provide a descriptive overview of clinical trials of EGb 761 in patients who met the diagnostic criteria for mild neurocognitive disorder (mild NCD) according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5). Methods: MEDLINE, PubMed and EMBASE were searched for randomized, placebo-controlled double-blind trials of EGb 761 in mild impairment of cognitive functioning. All trials involving patients who met retrospectively applied diagnostic criteria for mild NCD were included. Trials of primary prevention of dementia and trials of combinations of medical treatments were excluded. Results: Among 298 records found in databases and 76 further records related to EGb 761 in references of systematic reviews, 9 reports on clinical trials involving 946 patients met the pre-specified criteria for inclusion. Beneficial effects of EGb 761 were seen in neuropsychological tests (8 of 9 studies), scales for neuropsychiatric symptoms (3 of 3 studies), geriatric rating scales (1 of 2 studies) and global ratings of change (1 of 1 study). Significant effects were found in several domains of cognition (memory, speed of processing, attention and executive functioning). Among the neuropsychiatric symptoms, depression (2 of 3 studies) and anxiety (1 of 1 study) were significantly improved. No differences between EGb 761 treatment and placebo were seen with regard to the rates of adverse events. Discussion: The included studies demonstrate treatment benefits of Ginkgo biloba extract EGb 761, mainly on cognitive deficits and neuropsychiatric symptoms, in patients with mild NCD. The drug was safe and well tolerated.

Is recovery from left-sided neglect based on changes in automatic attention? An auditory event related potentials study.

An automatic spatial attention deficit is the primary deficit in neglect. However, the cognitive processes enabling recovery from neglect have rarely been studied. We used event-related potentials (ERP) to analyze if recovery is based on changes in automatic attention components. Twelve sub-acute patients with left visuospatial neglect were included. They received 3 weeks of intensive treatment. ERPs were recorded using two auditory paradigms: either a tone was presented randomly to the right or left ear (ATP) or as a Posner paradigm (PP) with left to right and vice versa moving cue tones and validly and invalidly cued target tones. Patients improved significantly on neuropsychological tests and neurological scales. For the ATP, no differences were observed related to the side of stimulation, but the auditory PP showed characteristic results, that is, smaller amplitudes for left-sided targets and higher amplitudes for invalid trials. Both paradigms revealed a treatment effect, but no changes were found in the amplitudes for the two target sides, which would be expected if the treatment would affect the automatic attention bias. Recovery from neglect seems not to be associated with changes in the automatic spatial attention bias, arguing that recovery might be due to higher cognitive compensatory processes.

Heart rate variability and fatigue in MS: two parallel pathways representing disseminated inflammatory processes?

BACKGROUND: Fatigue is a disabling symptom of multiple sclerosis. Its biological causes are still poorly understood. Several years ago, we proposed that fatigue might be the subjective representation of inflammatory processes. An important step for a straight-forward evaluation of our model would be to show that the level of fatigue is associated with vagal activation. The heart rate is under partial control of the vagus nerve. Using power spectrum analysis allows to separate, at least partly, sympathetic and parasympathetic impact on heart rate variability. METHODS: This narrative review summarizes the evidence for heart rate variability changes in MS patients, their relationship with fatigue and disease course. To do this, we conducted a literature search, including 45 articles relevant to the topic treated in this review. RESULTS: We illustrate that (1) inflammation leads to a change in cardiac behavior during acute and chronic phases, both in animals and in humans; (2) MS patients show changes of heart rate variability (HRV) that resemble those during acute and chronic inflammation due to multiple causes; (3) existing evidence favors a set of specific predictions about fatigue and parallel HRV changes; and (4) that MS-related brainstem lesions or neurological impairments do not completely explain HRV changes, leaving enough place for an explanatory relation between HRV and fatigue. DISCUSSION: We discuss the results of this review in relation to our model of fatigue and propose several observational and experimental studies that could be conducted to gain a better insight into whether fatigue and HRV can be interpreted as a common pathway, both reflecting activated autoimmune processes in MS patients.

Does culture shape our understanding of others' thoughts and emotions? An investigation across 12 countries.

Measures of social cognition have now become central in neuropsychology, being essential for early and differential diagnoses, follow-up, and rehabilitation in a wide range of conditions. With the scientific world becoming increasingly interconnected, international neuropsychological and medical collaborations are burgeoning to tackle the global challenges that are mental health conditions. These initiatives commonly merge data across a diversity of populations and countries, while ignoring their specificity. OBJECTIVE: In this context, we aimed to estimate the influence of participants' nationality on social cognition evaluation. This issue is of particular importance as most cognitive tasks are developed in highly specific contexts, not representative of that encountered by the world's population. METHOD: Through a large international study across 18 sites, neuropsychologists assessed core aspects of social cognition in 587 participants from 12 countries using traditional and widely used tasks. RESULTS: Age, gender, and education were found to impact measures of mentalizing and emotion recognition. After controlling for these factors, differences between countries accounted for more than 20% of the variance on both measures. Importantly, it was possible to isolate participants' nationality from potential translation issues, which classically constitute a major limitation. CONCLUSIONS: Overall, these findings highlight the need for important methodological shifts to better represent social cognition in both fundamental research and clinical practice, especially within emerging international networks and consortia. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Treatment of Fabry Disease management with migalastat-outcome from a prospective 24 months observational multicenter study (FAMOUS).

AIMS: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by a deficiency of the lysosomal enzyme α-galactosidase A (GLA/AGAL), resulting in the lysosomal accumulation of globotriaosylceramide (Gb3). Patients with amenable GLA mutations can be treated with migalastat, an oral pharmacological chaperone increasing endogenous AGAL activity. In this prospective observational multicentre study, safety as well as cardiovascular, renal, and patient-reported outcomes and disease biomarkers were assessed after 12 and 24 months of migalastat treatment under 'real-world' conditions. METHODS AND RESULTS: A total of 54 patients (26 females) (33 of these [61.1%] pre-treated with enzyme replacement therapy) with amenable mutations were analysed. Treatment was generally safe and well tolerated. A total of 153 events per 1000 patient-years were detected. Overall left ventricular mass index decreased after 24 months (all: -7.5 ± 17.4 g/m2, P = 0.0118; females: -4.6 ± 9.1 g/m2, P = 0.0554; males: -9.9 ± 22.2 g/m2, P = 0.0699). After 24 months, females and males presented with a moderate yearly loss of estimated glomerular filtration rate (-2.6 and -4.4 mL/min/1.73 m2 per year; P = 0.0317 and P = 0.0028, respectively). FD-specific manifestations/symptoms remained stable (all P > 0.05). A total of 76.9% of females and 50% of males suffered from pain, which has not improved under treatment. FD-specific disease scores (Disease Severity Scoring System and Mainz Severity Score Index) remained stable during treatment. AGAL activities and plasma lyso-Gb3 values remained stable, although some male patients presented with increasing lyso-Gb3 levels over time. CONCLUSIONS: Treatment with migalastat was generally safe and resulted in most patients in an amelioration of left ventricular mass. However, due to the heterogeneity of FD phenotypes, it is advisable that the treating physician monitors the clinical response regularly.

Structured Delirium Management in the Hospital.

BACKGROUND: Delirium is a common and serious complication of inpatient hospital care in older patients. The current approaches to prevention and treatment followed in German hospitals are inconsistent. The aim of this study was to test the effectiveness of a standardized multiprofessional approach to the management of delirium in inpatients. METHODS: The patients included in the study were all >65 years old, were treated for at least 3 days on an internal medicine, trauma surgery, or orthopedic ward at Münster University Hospital between January 2016 and December 2017, and showed cognitive deficits on standardized screening at the time of admission (a score of ≤=25 on the Montreal Cognitive Assessment [MoCA] test). Patients in the intervention group received standardized delirium prevention and treatment measures; those in the control group did not. The primary outcomes measured were the incidence and duration of delirium during the hospital stay; the secondary outcomes measured were cognitive deficits relevant to daily living at 12 months after discharge (MoCA and Instrumental Activities of Daily Living [I-ADL]). RESULTS: The data of 772 patients were analyzed. Both the rate and the duration of delirium were lower in the intervention group than in the control group (6.8% versus 20.5%, odds ratio 0.28, 95% confidence interval [0.18; 0.45]; 3 days [interquartile range, IQR 2-4] versus 6 days [IQR 4-8]). A year after discharge, the patients with delirium in the intervention group showed fewer cognitive deficits relevant to daily living than those in the control group (I-ADL score 2.5 [IQR 2-4] versus 1 [IQR 1-2], P = 0.02). CONCLUSION: Structured multiprofessional management reduces the incidence and duration of delirium and lowers the number of lasting cognitive deficits relevant to daily living after hospital discharge.

Utility of the Repeat and Point Test for Subtyping Patients With Primary Progressive Aphasia.

BACKGROUND: Primary progressive aphasia (PPA) may present with three distinct clinical sybtypes: semantic variant PPA (svPPA), nonfluent/agrammatic variant PPA (nfvPPA), and logopenic variant PPA (lvPPA). OBJECTIVE: The aim was to examine the utility of the German version of the Repeat and Point (R&P) Test for subtyping patients with PPA. METHOD: During the R&P Test, the examiner reads out aloud a noun and the participants are asked to repeat the word and subsequently point to the corresponding picture. Data from 204 patients (68 svPPA, 85 nfvPPA, and 51 lvPPA) and 33 healthy controls were analyzed. RESULTS: Controls completed both tasks with >90% accuracy. Patients with svPPA had high scores in repetition (mean=9.2±1.32) but low scores in pointing (mean=6±2.52). In contrast, patients with nfvPPA and lvPPA performed comparably in both tasks with lower scores in repetition (mean=7.4±2.7 for nfvPPA and 8.2±2.34 for lvPPA) but higher scores in pointing (mean=8.9±1.41 for nfvPPA and 8.6±1.62 for lvPPA). The R&P Test had high accuracy discriminating svPPA from nfvPPA (83% accuracy) and lvPPA (79% accuracy). However, there was low accuracy discriminating nfvPPA from lvPPA (<60%). CONCLUSION: The R&P Test helps to differentiate svPPA from 2 nonsemantic variants (nfvPPA and lvPPA). However, additional tests are required for the differentiation of nfvPPA and lvPPA.

Motor speech disorders in the nonfluent, semantic and logopenic variants of primary progressive aphasia.

OBJECTIVE: Motor speech disorders (MSDs) are characteristic for nonfluent primary progressive aphasia (nfvPPA). In primary progressive aphasia (PPA) of the semantic (svPPA) and of the logopenic type (lvPPA), speech motor function is considered typically intact. However, knowledge on the prevalence of MSDs in svPPA and lvPPA is mainly based on studies with a priori knowledge of PPA syndrome diagnosis. This fully blinded retrospective study aims to provide data on the prevalence of all types of MSDs in a large sample of German-speaking patients with different subtypes of PPA. METHOD: Two raters, blinded for PPA subtype, independently evaluated connected speech samples for MSD syndrome and severity from 161 patients diagnosed with nfvPPA, svPPA or lvPPA in the database of the German Consortium of Frontotemporal Lobar Degeneration (FTLDc). In case of disagreement, a third experienced rater re-evaluated the speech samples, followed by a consensus procedure. Consensus was reached for 160 patients (74 nfvPPA, 49 svPPA, 37 lvPPA). MAIN RESULTS: Across all PPA syndromes, 43.8% of the patients showed MSDs. Patients with nfvPPA demonstrated the highest proportion of MSDs (62.2%), but MSDs were also identified in svPPA (26.5%) and lvPPA (29.7%), respectively. Overall, dysarthria was the most common class of MSDs, followed by apraxia of speech. In addition, we identified speech abnormalities presenting as "syllabic speech", "dysfluent speech", and "adynamic speech". DISCUSSION: Our study confirmed MSDs as frequently occurring in PPA. The study also confirmed MSDs to be most common in patients with nfvPPA. However, MSDs were also found in substantial proportions of patients with svPPA and lvPPA. Furthermore, our study identified speech motor deficits that have not received attention in previous studies on PPA. The results are discussed against the background of the existing literature on MSDs in PPA, including theoretical considerations of the neuroanatomical conditions described for each of the different subtypes of PPA.

Oral and Periodontal Health in Patients with Alzheimer's Disease and Other Forms of Dementia - A Cross-sectional Pilot Study.

PURPOSE: Systemic inflammation is characteristic for the pathogenesis of Alzheimer's disease (AD) and is responsible for the accumulation of its disease-specific Tau-protein and ß-amyloid plaques. Studies focusing on an association with periodontitis showed worse periodontal conditions in patients with dementia, but until now, no study has investigated the differences between AD and other forms of dementia (noAD/DEM). Expecting severe periodontal disease in AD, the aim of this pilot-study was to compare the periodontal and dental status in patients with either AD or noAD/DEM. MATERIALS AND METHODS: Twenty patients recently diagnosed with AD and 20 with noAD/DEM between the ages of 50 and 70 years were recruited at the Department of Neurology, University Hospital, Münster, Germany and clinically examined at the Department of Periodontology, School of Dental Medicine, Münster, Germany. Neuropsychological testing, levels of Tau-protein and ß-amyloid in serum and liquor were used to distinguish between both groups. Dental and periodontal parameters such as clinical attachment loss (CAL), probing pocket depth (PPD), bleeding-on-probing (BOP), radiographic bone loss, full-mouth plaque score (FMPS), and missing and restored teeth were recorded. RESULTS: Periodontitis was diagnosed in all patients. Patients with AD presented mean BOP of 54.7 ± 31.1% and radiographic bone loss of 42.5 ± 25.3%; the mean BOP of those with noAD/DEM was 52.0 ± 23.7% and radiographic bone loss was 40.9 ± 32.3%. There was also no statistically significant difference regarding other periodontal and dental parameters. CONCLUSIONS: Both patients with AD and noAD/DEM had periodontal disease. Consequently, patients with all forms of dementia (AD/other) need special dental care to improve periodontal and oral health.

Treatment switch in Fabry disease- a matter of dose?

BACKGROUND: Patients with Fabry disease (FD) on reduced dose of agalsidase-beta or after switch to agalsidase-alfa show a decline in chronic kidney disease epidemiology collaboration-based estimated glomerular filtration rate (eGFR) and a worsened plasma lyso-Gb3 decrease. Hence, the most effective dose is still a matter of debate. METHODS: In this prospective observational study, we assessed end-organ damage and clinical symptoms in 78 patients who had received agalsidase-beta (1.0 mg/kg) for >1 year, which were assigned to continue this treatment (agalsidase-beta, regular-dose group, n=17); received a reduced dose of agalsidase-beta and subsequent switch to agalsidase-alfa (0.2 mg/kg) or a direct switch to 0.2 mg/kg agalsidase-alfa (switch group, n=22); or were re-switched to agalsidase-beta after receiving agalsidase-alfa for 12 months (re-switch group, n=39) with a follow-up of 88±25 months. RESULTS: No differences for clinical events were observed for all groups. Patients within the re-switch group started with the worst eGFR values at baseline (p=0.0217). Overall, eGFR values remained stable in the regular-dose group (p=0.1052) and decreased significantly in the re-switch and switch groups (p<0.0001 and p=0.0052, respectively). However, in all groups males presented with an annual loss of eGFR by -2.9, -2.5 and -3.9 mL/min/1.73 m² (regular-dose, re-switch, switch groups, all p<0.05). In females, eGFR decreased significantly only in the re-switch group by -2.9 mL/min/1.73 m² per year (p<0.01). Lyso-Gb3 decreased in the re-switch group after a change back to agalsidase-beta (p<0.05). CONCLUSIONS: Our data suggest that a re-switch to high dosage of agalsidase results in a better biochemical response, but not in a significant renal amelioration especially in classical males.

Postoperative delirium - treatment and prevention.

PURPOSE OF REVIEW: Postoperative delirium (POD) is one of the most severe complications after surgery.The consequences are dramatic: longer hospitalization, a doubling of mortality and almost all cases develop permanent, yet subtle, cognitive deficits specific to everyday life. Actually, no global guideline with standardized concepts of management exists. Advances in prevention, diagnosis and treatment can improve recognition and risk stratification of delirium and its consequences. RECENT FINDINGS: Management of POD is a multiprofessional approach and consists of different parts: First, the detection of high-risk patients with a validated tool, preventive nonpharmacological concepts and an intraoperative anesthetic management plan that is individualized to the older patient (e.g. avoiding large swings in blood pressure, vigilance in maintaining normothermia, ensuring adequate analgesia and monitoring of anesthetic depth). In addition to preventive standards, treatment and diagnostic concepts must also be available, both pharmaceutical and nonpharmacological. SUMMARY: Not every POD can be prevented. It is important to detect patients with high risk for POD and have standardized concepts of management. The most important predisposing risk factors are a higher age, preexisting cognitive deficits, multimorbidity and an associated prodelirious polypharmacy. In view of demographic change, the implementation of multidisciplinary approaches to pharmacological and nonpharmacological POD management is highly recommended.

Case Report: A Spinal Ischemic Lesion in a 24-Year-Old Patient With Fabry Disease.

Background: While cerebral lesions are common in Fabry disease (FD), spinal lesions have not been described, and their presence was suggested to be indicative of multiple sclerosis. Here, we present a FD patient with histopathological confirmed spinal ischemic stroke. Case presentation: A patient with genetically and biochemically diagnosed FD and characteristic manifestations (acroparesthesia, angiokeratomas, hypohidrosis, microalbuminuria, myocardial hypertrophy) presented with paraplegia, loss of all sensory modalities below Th9, and loss of bowel and bladder function. While cranial MRI was inconspicuous, spinal MRI showed a T2 hyperintense, non-contrast-enhancing lesion of the thoracic spinal cord. Lumbar puncture revealed mild pleocytosis, increased total protein and lactate levels, decreased glucose ratio, and negative oligoclonal bands. Rheumatic, neoplastic, and infectious disorders were excluded. The patient received intravenous and intrathecal methylprednisolone, plasmapheresis, intravenous immunoglobulins, and cyclophosphamide without clinical improvement. A biopsy of the thoracic lesion was performed. A histopathological examination revealed necrotic tissue consistent with spinal cord ischemia. Diagnostic work-up for stroke etiology clarification was not conspicuous. Two years onward, the patient suffered from a pontine infarction and a transient ischemic attack. Conclusion: The current case highlights the possible occurrence of spinal ischemic lesions in FD. Thus, the diagnosis of FD should not be prematurely discarded in the presence of spinal lesions.

Assessment of Peripheral Nervous System Alterations in Patients with the Fabry Related GLA-Variant p.A143T.

Background The purpose of this study is to examine alterations of the peripheral nervous system (PNS) in oligo-symptomatic patients carrying the Fabry related GLA-gene variant p.A143T by Magnetic Resonance Neurography (MRN) and skin biopsy. This prospective study assessed dorsal root ganglia (DRG) volume L3 to S2, vascular permeability of the DRG L5, S1, and the spinal nerve L5 in five patients carrying p.A143T in comparison to patients with classical Fabry mutations and healthy controls. Moreover, skin punch biopsies above the lateral malleolus of the right foot were obtained in four patients and intraepidermal nerve fiber density (IENFD) was counted individually. Compared to controls, DRG volumes of p.A143T patients were enlarged by 30% (L3, p < 0.05), 35% (L4, p < 0.05), 29% (L5, p = 0.15), 36% (S1, p < 0.01), and 18% (S2, p < 0.05), but less pronounced compared to patients carrying a classical Fabry mutation. Compared to healthy controls, vascular permeability was decreased by 40% (L5 right), 49% (L5 left), 48% (S1 right), and 49% (S1) (p < 0.01-p < 0.001), but non-significant less than patients carrying a classical Fabry mutation. Compared to sex-matched 5% lower normative reference values per decade, IENFD was decreased in three of four patients. MRN and determination of IENFD is able to detect early alteration of the PNS segment in oligo-symptomatic patients with the disease-modifying GLA-variant p.A143T on an individual basis. This procedure might also help in further GLA-variants of uncertain significance for early identification of patients with single major organ manifestation.