Abnormal dopamine transporter imaging in pure autonomic failure: a potential biomarker of central nervous system involvement.

BACKGROUND AND PURPOSE: Pure autonomic failure (PAF) is a rare progressive neurodegenerative disease characterized by neurogenic orthostatic hypotension at presentation, without other neurological abnormalities. Some patients may develop other central neurological features indicative of multiple system atrophy or a Lewy body disorder. There are currently no biomarkers to assess possible central nervous system involvement in probable PAF at an early stage. A possibility is to evaluate the nigrostriatal dopaminergic degeneration by imaging of dopamine transporter with DaTscan brain imaging. The objective was to evaluate subclinical central nervous system involvement using DaTscan in PAF. METHODS: We retreospectively reviewed pure autonomic failure patients who were evaluated at the Autonomic Unit between January 2015 and August 2021 and underwent comprehensive autonomic assessment, neurological examination, brain magnetic resonance imaging and DaTscan imaging. DaTscan imaging was performed if patients presented with atypical features which did not meet the criteria for Parkinson's disease or multiple system atrophy or other atypical parkinsonism. RESULTS: In this cohort, the median age was 49.5 years at disease onset, 57.5 years at presentation, and the median disease duration was 7.5 years. Five of 10 patients had an abnormal DaTscan without neurological features meeting the criteria of an alternative diagnosis. Patients with abnormal DaTscan were predominantly males, had shorter disease duration and had more severe genitourinary symptoms. DISCUSSION: Degeneration of nigrostriatal dopaminergic neurons measured using DaTscan imaging can present in patients with PAF without concurrent signs indicating progression to widespread α-synucleinopathy. It is advocated that DaTscan imaging should be considered as part of the workup of patients with emerging autonomic failure who are considered to have PAF.

Impaired cholinergic integrity of the colon and pancreas in dementia with Lewy bodies.

Dementia with Lewy bodies is characterized by a high burden of autonomic dysfunction and Lewy pathology in peripheral organs and components of the sympathetic and parasympathetic nervous system. Parasympathetic terminals may be quantified with 18F-fluoroetoxybenzovesamicol, a PET tracer that binds to the vesicular acetylcholine transporter in cholinergic presynaptic terminals. Parasympathetic imaging may be useful for diagnostics, improving our understanding of autonomic dysfunction and for clarifying the spatiotemporal relationship of neuronal degeneration in prodromal disease. Therefore, we aimed to investigate the cholinergic parasympathetic integrity in peripheral organs and central autonomic regions of subjects with dementia with Lewy bodies and its association with subjective and objective measures of autonomic dysfunction. We hypothesized that organs with known parasympathetic innervation, especially the pancreas and colon, would have impaired cholinergic integrity. To achieve these aims, we conducted a cross-sectional comparison study including 23 newly diagnosed non-diabetic subjects with dementia with Lewy bodies (74 ± 6 years, 83% male) and 21 elderly control subjects (74 ± 6 years, 67% male). We obtained whole-body images to quantify PET uptake in peripheral organs and brain images to quantify PET uptake in regions of the brainstem and hypothalamus. Autonomic dysfunction was assessed with questionnaires and measurements of orthostatic blood pressure. Subjects with dementia with Lewy bodies displayed reduced cholinergic tracer uptake in the pancreas (32% reduction, P = 0.0003) and colon (19% reduction, P = 0.0048), but not in organs with little or no parasympathetic innervation. Tracer uptake in a region of the medulla oblongata overlapping the dorsal motor nucleus of the vagus correlated with autonomic symptoms (rs = -0.54, P = 0.0077) and changes in orthostatic blood pressure (rs = 0.76, P < 0.0001). Tracer uptake in the pedunculopontine region correlated with autonomic symptoms (rs = -0.52, P = 0.0104) and a measure of non-motor symptoms (rs = -0.47, P = 0.0230). In conclusion, our findings provide the first imaging-based evidence of impaired cholinergic integrity of the pancreas and colon in dementia with Lewy bodies. The observed changes may reflect parasympathetic denervation, implying that this process is initiated well before the point of diagnosis. The findings also support that cholinergic denervation in the brainstem contributes to dysautonomia.

Evaluating Diagnostic Ultrasound of the Vagus Nerve as a Surrogate Marker for Autonomic Neuropathy in Diabetic Patients.

Background and Objectives: Diagnostic ultrasound of the vagus nerve has been used to examine different polyneuropathies, and it has been suggested to be useful as a marker of autonomic dysfunction in diabetic patients. Materials and Methods: We analyzed the cross-sectional area (CSA) of the right vagus nerve of 111 patients with type 2 diabetes in comparison to 104 healthy adults and 41 patients with CIDP (chronic inflammatory demyelinating polyneuropathy). In the diabetes group, sympathetic skin response (SSR) was measured as an indicator for autonomic neuropathy. Carotid intima-media thickness (CIMT) was measured as a surrogate for atherosclerosis. Clinical symptoms of polyneuropathy were assessed using the Neuropathy Symptom Score and the Neuropathy Disability Score. Results: In total, 61.3% of the diabetes patients had clinical signs of polyneuropathy; 23.4% had no SSR at the feet as an indicator of autonomic neuropathy. Mean vagus nerve CSA did not differ in patients with and without diabetic polyneuropathy or in diabetic patients with and without SSR at the feet. No significant correlation was found between vagus nerve CSA and CIMT or SSR parameters in diabetic patients. Mean CSA of the right vagus nerve was slightly larger in diabetic patients (p = 0.028) and in patients with CIDP (p = 0.015) than in healthy controls. Conclusions: Effect sizes and mean differences were rather small so that a reliable diagnosis cannot be performed based on the vagus nerve measurement of a single person alone. Vagus nerve CSA seems not suitable as an indicator of autonomic dysfunction or cardiovascular risk in diabetic patients.

The High-Resolution Three-Dimensional Magnetic Detector System 3D-Magma Accurately Measures Gastric and Small Bowel Motility in People with Type 2 Diabetes with Neuropathy.

Gastroparesis is an important complication of diabetes. Motility disorders are underdiagnosed and can lead to unexplained hypoglycemia. Currently diagnostic options are limited. All established methods harbor certain disadvantages. The 3D-MAGMA system is capable of reliably measuring gastric and small intestinal motility. The aim of the current study was to determine if 3D-MAGMA is able to detect changes in intestinal motility in people with type 2 diabetes. 18 healthy volunteers and 19 people with type 2 diabetes underwent motility testing by 3D-MAGMA. In the control group the retention time in the stomach was 33.0 [min] compared to 75.3 [min] in the diabetes group. The median time in the duodenum was 12.7 [min] compared to 8.1 [min]. The time for the first 50 cm of the jejunum was 29.9 [min] compared to 28.2 [min]. Discussion and conclusion: 3D-MAGMA is able to detect changes in intestinal motility. Its clinical value might be useful in patients with fluctuating blood glucose levels and unexplained hypoglycemic episodes.

Autonomic disorders and myocardial 123I-metaiodobenzylguanidine scintigraphy in Huntington's disease.

BACKGROUND: Huntington's disease (HD) patients often present with abnormal modulation of blood pressure and heart rate. We investigated whether cardiac autonomic innervation assessed by 123I-metaiodobenzylguanidine (MIBG) imaging is impaired in HD patients, in comparison with controls (Ctrl). METHODS: Fifteen patients (6 F and 9 M) were assessed by the motor section of the Unified HD Rating Scale, the Total Function Capacity, and the scale for outcomes in Parkinson's disease-autonomic (SCOPA-AUT) questionnaire. All patients and 10 Ctrl (5 F and 5 M) underwent 123I-MIBG imaging. From planar images, the early and late heart-to-mediastinum (H/M) ratios and myocardial washout rates (WR) were calculated. RESULTS: We did not find significant differences in early and late H/M ratios and WR between the two groups. At individual level, three patients showed reduced early and/or late H/M ratios. The most common autonomic complaints were gastrointestinal and genitourinary disorders. SCOPA-AUT questionnaire score results positively correlated with the disease duration and WR. CONCLUSIONS: Our study indicates that myocardial postganglionic sympathetic innervation is essentially preserved or only minimally involved in HD. These findings suggest that the cardiovascular dysfunction might be mainly due to the impairment of brain areas associated with the regulation and modulation of the heart function.

Multimodal assessment of autonomic dysfunction in amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with predominant progressive degeneration of motor neurons and motor deficits, but non-motor symptoms (NMS) such as cognitive and behavioural deficits are frequent and underestimated in current diagnostic pathways. Autonomic dysfunction has occasionally been described, although its frequency and relevance are unclear. The aim of this study was to investigate the role of the autonomic nervous system in ALS using a multimodal approach. METHODS: Thirty-seven ALS patients and 40 healthy sex- and age-matched controls were included. NMS were studied with the NMS assessment scale for Parkinson's disease and an autonomic subscale was calculated. Cardioautonomic innervation at rest and whilst standing was assessed by different parameters of heart rate variability. Morphological changes (cross-sectional area) of the vagus and median nerves for control were measured with high-resolution ultrasound. RESULTS: Non-motor symptoms in general were more frequent in ALS patients and correlated inversely with the ALS Functional Rating Scale whereas the autonomic subscore of the NMS assessment scale for Parkinson's disease did not differ between the two groups and was not related to functional impairment. Cardioautonomic assessment solely revealed an increased heart rate at rest in ALS patients, whereas the other heart rate variability parameters did not differ from controls. Structural sonographic investigation of the vagus and median nerves was similar in both groups. CONCLUSIONS: Using a multimodal approach evidence was found for a rather mild cardio-sympathetic overactivity in ALS patients. Overall, autonomic dysfunction seems to be subtle and is not related to the functional state of ALS patients.

Neuromuscular amyloidosis: Unmasking the master of disguise.

Amyloidosis refers to an etiologically heterogeneous group of protein misfolding diseases, pathologically characterized by extracellular amyloid fibrils producing congophillic amorphous deposits in organs and tissues, which may lead to severe organ dysfunction and mortality. Clinical presentations vary and are often nonspecific, depending on what organs or tissues are affected. In systemic amyloidosis, the peripheral nervous system is commonly affected, whereas the skeletal muscles are only rarely involved. Immunoglobulin light chain (AL) amyloidosis and hereditary transthyretin (ATTRv) amyloidosis are the most frequent types of systemic amyloidosis involving the neuromuscular system. Localized amyloidosis can occur in skeletal muscle, so-called isolated amyloid myopathy. Amyloid neuropathy typically involves small myelinated and unmyelinated sensory and autonomic nerve fibers early in the course of the disease, followed by large myelinated fiber sensory and motor deficits. The relentlessly progressive nature with motor, painful sensory and severe autonomic dysfunction, profound weight loss, and systemic features are distinct characteristics of amyloid neuropathy. Amyloid myopathy presentation differs between systemic amyloidosis and isolated amyloid myopathy. Long-standing symptoms, distal predominant myopathy, markedly elevated creatine kinase level, and lack of peripheral neuropathy or systemic features are highly suggestive of isolated amyloid myopathy. In ATTR and AL amyloidosis, early treatment correlates with favorable outcomes. Therefore, awareness of these disorders and active screening for amyloidosis in patients with neuropathy or myopathy are crucial in detecting these patients in the everyday practice of neuromuscular medicine. Herein, we review the clinical manifestations of neuromuscular amyloidosis and provide a diagnostic approach to this disorder.

Meta-iodobenzylguanidine myocardial scintigraphy in Perry disease.

INTRODUCTION: Perry disease (Perry syndrome), a hereditary TAR DNA-binding protein 43 (TDP-43) proteinopathy, is caused by dynactin subunit 1 (DCNT1) mutations and is characterized by rapidly progressive parkinsonism accompanied by depression, apathy, unexpected weight loss, and respiratory symptoms including central hypoventilation and central sleep apnea. Meta-iodobenzylguanidine (MIBG) myocardial scintigraphy is considered a diagnostic biomarker for Lewy body disease (LBD), as denervation of cardiac sympathetic nerves is a pathological feature in LBD. However, our previous studies have reported a decreased cardiac uptake of MIBG in patients with Perry disease. In this study, we aimed to correlate the MIBG myocardial scintigraphy findings with clinical features in Perry disease. METHODS: We evaluated data obtained from a multicenter survey of patients of Japanese origin with suspected Perry disease, who visited neurology departments in Japan from January 2010 to December 2018. We screened each patient's DNA for the DCTN1 mutation using Sanger sequencing and obtained the clinical details of all patients including findings from their MIBG myocardial scintigraphy. RESULTS: We identified two novel mutations, p.G71V and p.K68E, in DCTN1 in patients from two different families. The majority of patients (7/8, 87.5%) showed a decrease in cardiac uptake (heart to mediastinum ratio) in MIBG myocardial scintigraphy. These patients commonly presented with symptoms related to autonomic dysfunction: constipation, fecal incontinence, urinary disturbance, and orthostatic hypotension. CONCLUSIONS: MIBG myocardial scintigraphy may be a useful biomarker of autonomic dysfunction in Perry disease.

Cardiac sympathetic innervation and vesicular storage in pure autonomic failure.

OBJECTIVE: Pure autonomic failure (PAF) is a rare disease characterized by neurogenic orthostatic hypotension (nOH), absence of signs of central neurodegeneration, and profound deficiency of the sympathetic neurotransmitter norepinephrine. Reports have disagreed about mechanisms of the noradrenergic lesion. Neuropathological studies have highlighted denervation, while functional studies have emphasized deficient vesicular sequestration of cytoplasmic catecholamines in extant neurons. We examined both aspects by a combined positron emission tomographic (PET) neuroimaging approach using 11 C-methylreboxetine (11 C-MRB), a selective ligand for the cell membrane norepinephrine transporter, to quantify interventricular septal myocardial noradrenergic innervation and using 18 F-dopamine (18 F-DA) to assess intraneuronal vesicular storage in the same subjects. METHODS: Seven comprehensively tested PAF patients and 11 controls underwent 11 C-MRB PET scanning for 45 minutes (dynamic 5X1', 3X5', 1X10', static 15 minutes) and 18 F-DA scanning for 30 minutes (same dynamic imaging sequence) after 3-minute infusions of the tracers on separate days. RESULTS: In the PAF group septal 11 C-MRB-derived radioactivity in the static frame was decreased by 26.7% from control (p = 0.012). After adjustment for nonspecific binding of 11 C-MRB, the PAF group had a 41.1% mean decrease in myocardial 11 C-MRB-derived radioactivity (p = 0.015). The PAF patients had five times faster postinfusion loss of 18 F-DA-derived radioactivity (70 ± 3% vs. 14 ± 8% by 30 minutes, p < 0.0001). At all time points after infusion of 18 F-DA and 11 C-MRB mean 18 F/11 C ratios in septal myocardium were lower in the PAF than control group. INTERPRETATION: PAF entails moderately decreased cardiac sympathetic innervation and a substantial vesicular storage defect in residual nerves.

18F-FDG-PET brain imaging may highlight brain metabolic alterations in dysautonomic syndrome after human papilloma virus vaccination.

AIM: The aim of this study was to evaluate brain glucose metabolism by means of [18F]-fluoro-deoxygluycose (F-FDG) PET in a group of patients presenting dysautonomic syndrome after human papilloma virus (HPV) immunization. METHODS: Medical records of patients, referred to the 'Second Opinion Medical Consulting Network' Medical Centre (Modena, Italy) diagnosed with dysautonomic syndrome were searched. Inclusion criteria were presence in the medical history of adverse drug reactions following HPV vaccine; a Montreal Cognitive Assessment score <25 and good quality of a F-FDG-PET brain scan performed within 12 months from the diagnosis of dysautonomic syndrome. F-FDG-PET images of patients (HPV-group) were compared to a control group, matched for age and sex, using statistical parametric mapping (SPM). RESULTS: The F-FDG-PET study was available for five female patients. The SPM-group analysis revealed significant hypometabolism (P < 0.05 false discovery rate corrected) in the right superior and medial temporal gyrus (Brodmann areas 22, 21) and insula (Brodmann area 13). At a threshold of P < 0.001 (uncorrected), further hypometabolic regions were revealed in the right superior temporal gyrus (Brodmann area 42) and caudate head and in the left superior temporal gyrus (Brodmann area 22), frontal subcallosal gyrus (Brodmann area 47) and insula (Brodmann area 13). Relative hypermetabolism (P = 0.001) was revealed in the right premotor cortex (Brodmann area 6). CONCLUSION: This study revealed the possibility of altered brain glucose metabolism in subjects with dysautonomic syndrome post-immunization with HPV vaccine. These results could reinforce the hypothesis of a causal relationship between HPV vaccine, or some component included in the vaccine and the development of clinical manifestations.

La disfunción autonómica en el paciente con enfermedad neurodegenerativa / Autonomic dysfunction in the patient with neurodegenerative disease

La disfunción autonómica es una enfermedad muy frecuente en las alfa-sinucleoinopatías (enfermedad de Parkinson, demencia por cuerpos de Lewy, atrofia multisistémica). A nivel cardiovascular puede producir síntomas como hipotensión ortostática, hipertensión supina o disminución de la respuesta de la frecuencia cardiaca a estímulos. Para el diagnóstico es fundamental una sospecha clínica y una exploración física minuciosa, tomando la presión arterial tanto en posición de decúbito supino como en bipedestación. El electrocardiograma puede mostrar un alargamiento de los intervalos PR y QT, mientras que la monitorización ambulatoria de presión arterial de 24 h aporta información sobre los patrones de presión arterial. La confirmación de la disfunción simpática cardiaca puede realizarse con una gammagrafía miocárdica de inervación con 123-I-metilbencilguanidina (123-I-MIBG), ya que refleja la captación noradrenérgica neuronal específica. A continuación presentamos el caso de un varón con enfermedad de Parkinson que tras un completo estudio fue diagnosticado de disfunción autonómica cardiovascular

Autonomic dysfunction is a common condition in the alpha-synucleinopathies (Parkinson's disease, dementia with Lewy bodies, multiple system atrophy). Cardiovascular symptoms may include orthostatic hypotension, supine hypertension or decreased heart rate response. A clinical suspicion and physical examination are essential for diagnosis, taking blood pressure in supine and standing positions. The electrocardiogram may show a prolongation of the PR and QT intervals, while 24-hour ambulatory blood pressure monitoring provides information on blood pressure patterns. Cardiac sympathetic dysfunction can be confirmed by an innervation myocardial scintigraphy with 123-I-methylbenzylguanidine (123-I-MIBG). This can reflect specific neuronal noradrenergic uptake.We present the case of a man with Parkinson's disease who was diagnosed with cardiovascular autonomic dysfunction after a complete study

Clinical and MRI correlates of autonomic dysfunction in neuromyelitis optica spectrum disorder.

BACKGROUND: The aim of this study was to investigate the relationship of autonomic dysfunction and clinical findings in patients with neuromyelitis optica spectrum disorder (NMOSD). METHODS: For the assessment of autonomic dysfunction, heart rate variability (HRV) and blood pressure (BP) measurement to deep breathing, Valsalva maneuver or head tilt-table test, with quantitative sudomotor axon reflex test (QSART) were used and interpreted in the form of the composite autonomic scoring scale (CASS). Clinical and radiological correlates with autonomic profiles were analyzed. RESULTS: A total of 27 patients (mean age, 44.4 ± 12.26 years; female: male=22:5) were enrolled in this study and 74.1% of them showed autonomic dysfunction, involving the adrenergic, cardiovagal, or sudomotor domains. Eighteen patients were during remission, in whom, demographics and MRI findings were associated with an index or a total score of CASS. The presence of cervical cord lesion showed the association with cardiovagal index (B = 0.750, S.E. 0.242, 95% CI 0.237-1.263, p = 0.007), male gender with sudomotor index (B = 1.600, S.E. 0.653, 95% CI 0.199-3.001, p = 0.028) and the involvement of brain and/or spinal cord with a total CASS score (B = 1.500, S.E. 0.655, 95% CI 0.096-2.904, p = 0.038). In multivariable analysis, delayed pressure recovery time showed a significant positive association with EDSS score (B = 0.103, S.E. 0.031, 95% CI 0.037-0.168, p = 0.004). DISCUSSION: Cardiovascular and sudomotor autonomic dysfunction are common in NMOSD. Several clinical and MRI characteristics of patients may warrant the investigation of autonomic dysfunction and its proper management.

Impaired orthostatic heart rate recovery is associated with smaller thalamic volume: Results from The Irish Longitudinal Study on Aging (TILDA).

The thalamus is a central hub of the autonomic network and thalamic volume has been associated with high-risk phenotypes for sudden cardiac death. Heart rate response to physiological stressors (e.g., standing) and the associated recovery patterns provide reliable indicators of both autonomic function and cardiovascular risk. Here we examine if thalamic volume may be a risk marker for impaired heart rate recovery in response to orthostatic challenge. The Irish Longitudinal Study on Aging involves a nationally representative sample of older individuals aged ≥50 years. Multimodal brain magnetic resonance imaging and orthostatic heart rate recovery were available for a cross-sectional sample of 430 participants. Multivariable regression and linear mixed-effects models were adjusted for head size, age, sex, education, body mass index, blood pressure, history of cardiovascular diseases and events, cardiovascular medication, diabetes mellitus, smoking, alcohol intake, timed up-and-go (a measure of physical frailty), physical exercise and depression. Smaller thalamic volume was associated with slower heart rate recovery (-1.4 bpm per 1 cm3 thalamic volume, 95% CI -2.01 to -0.82; p < .001). In multivariable analysis, participants with smaller thalamic volumes had a mean heart rate recovery -2.7 bpm slower than participants with larger thalamic volumes (95% CI -3.89 to -1.61; p < .001). Covariates associated with smaller thalamic volume included age, history of diabetes, and heavy alcohol consumption. Thalamic volume may be an indicator of the structural integrity of the central autonomic network. It may be a clinical biomarker for stratification of individuals at risk of autonomic dysfunction, cardiovascular events, and sudden cardiac death.

Non-motor symptoms and striatal dopamine transporter binding in early Parkinson's disease.

BACKGROUND: Non-motor symptoms (NMS) are common in Parkinson's disease (PD), but their relationships to nigrostriatal degeneration remain largely unexplored. METHODS: We evaluated 18 NMS scores covering 5 major domains in relation to concurrent and future dopamine transporter (DAT) imaging in 344 PD patients from the Parkinson's Progression and Markers Initiative (PPMI). We standardized NMS assessments into z-scores for side-by-side comparisons. Patients underwent sequential DaTSCAN imaging at enrollment and at months 12, 24, and 48. Specific binding ratios (SBR) were calculated using the occipital lobe reference region. We evaluated the association of striatal DAT binding at the four time points with each baseline NMS using mixed-effects regression models. RESULTS: Multiple baseline NMS were significantly associated with DAT binding at baseline and at follow-up scans. REM sleep behavior disorder (RBD) symptoms showed the strongest association - mean striatal SBR declined with increasing RBD symptom z-score (average of time-point-specific slopes per unit change in z-score: ßAVG = -0.083, SE = 0.017; p < 0.0001). In addition, striatal DAT binding was linearly associated with increasing baseline z-scores: positively for the memory (ßAVG=0.055, SE = 0.022; p = 0.01) and visuospatial (ßAVG=0.044, SE = 0.020; p = 0.03) cognitive domains, and negatively for total anxiety (ßAVG= -0.059, SE = 0.018; p = 0.001). Striatal DAT binding showed curvilinear associations with odor identification, verbal discrimination recognition, and autonomic dysfunction z-scores (p = 0.001, p = 0.0009, and p = 0.0002, respectively). Other NMS were not associated with DAT binding. CONCLUSIONS: Multiple NMS, RBD symptoms in particular, are associated with nigrostriatal dopaminergic changes in early PD.

Imaging cardiac innervation in hereditary transthyretin (ATTRm) amyloidosis: A marker for neuropathy or cardiomyopathy in case of heart failure?

BACKGROUND: Nuclear imaging modalities using 123Iodine-metaiodobenzylguanidine (123I-MIBG) and bone seeking tracers identify early cardiac involvement in ATTRm amyloidosis patients. However, little is known whether results from 123I-MIBG scintigraphy actually correlate to markers for either cardiac autonomic neuropathy or cardiomyopathy. METHODS: All TTR mutation carriers and ATTRm patients who underwent both 123I-MIBG and 99mTechnetium-hydroxymethylene diphosphonate (99mTc-HDP) scintigraphy were included. Cardiomyopathy was defined as NT-proBNP > 365 ng/L, and cardiac autonomic neuropathy as abnormal cardiovascular reflexes at autonomic function tests. Late 123I-MIBG heart-to-mediastinum ratio (HMR) < 2.0 or wash-out > 20%, and any cardiac 99mTc-HDP uptake were considered as abnormal. RESULTS: 39 patients (13 carriers and 26 ATTRm patients) were included in this study. Patients with cardiomyopathy, with or without cardiac autonomic neuropathy, had lower late HMR than similar patients without cardiomyopathy [median 1.1 (range 1.0-1.5) and 1.5(1.2-2.6) vs 2.4 (1.4-3.8) and 2.5 (1.5-3.7), respectively, P < 0.001]. Late HMR and wash-out (inversely) correlated with NT-proBNP r = - 0.652 (P < 0.001) and r = 0.756 (P < 0.001), respectively. Furthermore, late HMR and wash-out (inversely) correlated with cardiac 99mTc-HDP uptake r = - 0.663 (P < 0.001) and r = 0.617 (P < 0.001), respectively. CONCLUSION: In case of heart failure, 123I-MIBG scintigraphy reflects cardiomyopathy rather than cardiac autonomic neuropathy in ATTRm patients and TTR mutation carriers. 123I-MIBG scintigraphy may already be abnormal before any cardiac bone tracer uptake is visible.

Influence of a neck compression collar on cerebrovascular and autonomic function in men and women.

OBJECTIVE: Neck compression collars have been proposed to reduce injury to the brain caused by head impacts. Our objective was to test if compression of the carotid artery affected the baroreflex and influenced blood pressure control. METHODS: Cerebrovascular and autonomic responses of healthy young men and women (n = 8 each) to paced deep breathing, Valsalva, and 70o head-up tilt with or without use of a Q-collar were determined. Continuous measurements of heart rate, beat-to-beat blood pressure, transcranial Doppler, and end-tidal gases were obtained. Heart rate variability was measured during supine rest and head-up tilt. Carotid artery and jugular vein cross-sectional area were measured at end-inhalation and end-exhalation using cross-sectional ultrasound images at diastole. RESULTS: Wearing the collar reduced carotid cross-sectional area (CSA; P = 0.022; η2 = 0.03) and increased jugular CSA (P = 0.001; η 2 = 0.30). In both men and women, wearing the collar increased systolic blood pressure during Valsalva (P<0.05; η 2 = 0.38). In only men, wearing the collar resulted in prolonged pressure recovery time during Valsalva (P = 0.02; η 2 = 0.05). In only women, wearing the collar increased baseline diastolic (P = 0.026; η 2 = 0.09) and mean (P = 0.041; η 2 = 0.06) middle cerebral artery (MCA) blood flow velocity, which attenuated the normal increase of diastolic (P = 0.01; η 2 = 0.03) and mean (P = 0.038; η 2 = 0.02) MCA blood flow velocity during Valsalva. There were no effects of sex or collar on the responses to deep breathing (P>0.05), and there were no effects of the collar on cerebrovascular function, hemodynamics, cardiovagal baroreceptor sensitivity, or heart rate variability (P>0.05) during upright tilt. CONCLUSION: Use of the Q-collar compresses both the jugular vein and carotid artery influencing sympathetic nerve activity in both men and women while influencing brain blood flow in women.

Neurovascular compression syndrome of the brain stem with opsoclonus-myoclonus syndrome combined with vestibular paroxysmia and autonomic symptoms.

We describe a rare case of neurovascular compression syndrome (NVCS) of the brain stem and opsoclonus-myoclonus syndrome (OMS) complicated with vestibular paroxysmia (VP) and autonomic symptoms. Moreover, we discuss the case with respect to the available information in medical literature. A 36-year-old man with vertigo and nausea had difficulty standing, and was transported by an ambulance to our hospital. He had VP, opsoclonus, cervical myoclonus, anxiety, and restless legs syndrome. Magnetic resonance imaging at hospitalization showed that the dolichoectatic vertebral artery was in contact with the postero-lateral side of the pontomedullary junction. He was diagnosed with NVCS of the brain stem (most likely of the input to the vestibular nucleus) associated with contact with the dolichoectatic vertebral artery. Combination therapy using multiple antiepileptic drugs, such as low-dose carbamazepine, clonazepam, and lacosamide, improved his clinical symptoms. He was finally able to walk and was discharged on day 42 after admission. He is being routinely followed-up since then. Further research is needed to confirm the validity of the combination therapy.