Impact of sleep quality and physical activity on blood pressure variability.

Increased blood pressure variability (BPV) is linked to cardiovascular disease and mortality, yet few modifiable BPV risk factors are known. We aimed to assess the relationship between sleep quality and activity level on longitudinal BPV in a cohort of community-dwelling adults (age ≥18) from 17 countries. Using Withings home measurement devices, we examined sleep quality and physical activity over one year, operationalized as mean daily step count and number of sleep interruptions, both transformed into tertiles. The primary study outcome was high BPV, defined as the top tertile of systolic blood pressure standard deviation. Our cohort comprised 29,375 individuals (mean age = 58.6 years) with 127.8±90.1 mean days of measurements. After adjusting for age, gender, country, body mass index, measurement days, mean blood pressure, and total time in bed, the odds ratio of having high BPV for those in the top tertile of sleep interruptions (poor sleep) was 1.37 (95% CI, 1.28-1.47) and 1.44 (95% CI, 1.35-1.54) for those in the lowest tertile of step count (physically inactive). Combining these exposures revealed a significant excess relative risk of 0.20 (95% CI, 0.04-0.35, p = 0.012), confirming their super-additive effect. Comparing individuals with the worst exposure status (lowest step count and highest sleep interruptions, n = 2,690) to those with the most optimal status (highest step count and lowest sleep interruptions, n = 3,531) yielded an odds ratio of 2.01 (95% CI, 1.80-2.25) for high BPV. Our findings demonstrate that poor sleep quality and physical inactivity are associated with increased BPV both independently and super-additively.

Symptomatic Treatment of Myelopathy.

OBJECTIVE: This article discusses the effects of myelopathy on multiple organ systems and reviews the treatment and management of some of these effects. LATEST DEVELOPMENTS: Recent advances in functional electrical stimulation, epidural spinal cord stimulation, robotics, and surgical techniques such as nerve transfer show promise in improving function in patients with myelopathy. Ongoing research in stem cell therapy and neurotherapeutic drugs may provide further therapeutic avenues in the future. ESSENTIAL POINTS: Treatment for symptoms of spinal cord injury should be targeted toward patient goals. If nerve transfer for upper extremity function is considered, the patient should be evaluated at around 6 months from injury to assess for lower motor neuron involvement and possible time limitations of surgery. A patient with injury at or above the T6 level is at risk for autonomic dysreflexia, a life-threatening condition that presents with elevated blood pressure and can lead to emergent hypertensive crisis. Baclofen withdrawal due to baclofen pump failure or programming errors may also be life-threatening. Proper management of symptoms may help avoid complications such as autonomic dysreflexia, renal failure, heterotopic ossification, and fractures.

Clinical Characteristics and Relevance of Dizziness in Patients with de novo Parkinson's Disease.

BACKGROUND: The purpose of this study was to determine the detailed characteristics of dizziness in patients with de novo Parkinson's disease (PD) and the clinical implications of dizziness. METHODS: Ninety-three people with de novo PD were enrolled between July 2017 and August 2022 for this retrospective study. Using each representative scale, various motor and non-motor symptoms were assessed. In addition, clinical manifestations of dizziness in those patients, including its presence, type, frequency, and duration of occurrence, were investigated. RESULTS: Thirty-nine patients with de novo PD reported dizziness, with presyncope being the most common (38%). The most common frequency was several times a week (51%). The most common duration was a few seconds (67%). Multivariable logistic regression analysis showed that dizziness was more common in women than in men {odds ratio (OR): 3.3601, 95% confidence interval (CI): 1.0820-10.4351, p = 0.0361}. Dizziness was significantly related to non-motor symptoms of low global cognition (OR: 0.8372, 95% CI: 0.7285-0.9622, p = 0.0123) and severe autonomic dysfunction (OR: 1.1112, 95% CI: 1.0297-1.1991, p = 0.0067). A post-hoc analysis revealed that dizziness was only associated with cardiovascular dysautonomia (adjusted OR: 10.2377, 95% CI: 3.3053-31.7098, p < 0.0001) among several domains of dysautonomia. CONCLUSIONS: About 42% of patients with de novo PD complained of dizziness. The occurrence of dizziness in those people was highly associated with female gender women, cognitive impairment, and cardiovascular dysautonomia. These results suggest that clinicians should pay close attention when patients with PD complain of dizziness.

A therapeutic challenge relating to the association of orthostatic hypotension and supine hypertension in a patient with cardiac autonomic neuropathy: a case report.

BACKGROUND: Cardiac autonomic neuropathy is a highly prevalent pathology in the diabetic population, and is the leading cause of death in this population. Orthostatic hypotension is the main clinical manifestation of the disease. In some patients, this orthostatic hypotension is associated with supine hypertension, posing a therapeutic challenge since treatment of one entity may aggravate the other. The challenge is to manage each of these two hemodynamic opposites without exposing the patient to a life-threatening risk of severe hypotension or hypertension. CASE PRESENTATION: We report a case of a 62-year-old ethnic Moroccan woman who has cardiovascular risk factors such as type 2 diabetes, arterial hypertension, and dyslipidemia. The patient's symptoms included dizziness, tremors, morning sickness, palpitations, and intolerance to exertion. Given her symptomatology, the patient benefited from an exploration of the autonomic nervous system through cardiovascular reactivity tests (Ewing tests), which confirmed the diagnosis of cardiac autonomic neuropathy. In addition to orthostatic hypotension, our patient had supine arterial hypertension, complicating management. To treat orthostatic hypotension, we advised the patient to avoid the supine position during the day, to raise the head of the bed during the night, and to have a sufficient fluid intake, with a gradual transition from decubitus to orthostatism and venous restraint of the lower limbs. Supine hypertension was treated with transdermal nitrates placed at bedtime and removed 1 hour before getting up. One week after the introduction of treatment, the patient reported a clear regression of functional symptoms, with an improvement in her quality of life. Improvement in symptomatology was maintained during quarterly follow-up consultations. CONCLUSIONS: Cardiac autonomic neuropathy is a very common pathology in diabetic patients. It is a serious condition with a life-threatening prognosis. Its management must be individualized according to the symptomatology and profile of each patient. The treatment of patients with orthostatic hypotension and supine hypertension requires special attention to ensure that each entity is treated without aggravating the other.

Effectiveness of Cerebrospinal Fluid Lumbar Drainage Among Patients with Aneurysmal Subarachnoid Hemorrhage: An Updated Systematic Review and Meta-Analysis.

INTRODUCTION: Cerebral vasospasm in patients after aneurysmal subarachnoid hemorrhage (aSAH) continues to be a major source of morbidity despite significant clinical and basic science research. The removal of blood and its degradation products from the subarachnoid space through prophylactic lumbar drainage (LD) is a favorable option. However, several studies have delivered conflicting conclusions on its efficacy after aSAH. METHODS: Systematic searches of Medline, Embase, and Cochrane Central Register of Controlled Trials were performed. The primary outcome was a good functional outcome (modified Rankin scale score, 0-2). Secondary outcomes included symptomatic vasospasm, secondary cerebral infarction, and mortality. RESULTS: A total of 14 studies reporting on 2473 patients with aSAH were included in the meta-analysis. Compared with the non-LD group, no significant differences were found in the rates of good functional outcomes in the LD group at discharge to 1 month (risk ratio [RR], 1.28; 95% confidence interval [CI], 0.64-2.58) or at 6 months (RR, 1.12; 95% CI, 0.97-1.41). These findings were consistent in the subgroup analyses of only randomized controlled trials or observational studies. LD was associated with lower rates of symptomatic vasospasm (RR, 0.61; 95% CI, 0.48-0.77), secondary cerebral infarction (RR, 0.59; 95% CI, 0.45-0.79), and mortality at discharge to 1 month (RR, 0.58; 95% CI, 0.41-0.82). The effect on mortality diminished at 6 months (RR, 0.70; 95% CI, 0.34-1.45). However, when analyzing only randomized controlled trials, the benefit of LD on lower rates of mortality continued even at 6 months (RR, 0.75; 95% CI, 0.58-0.99). CONCLUSIONS: For aSAH patients, the use of LD is associated with benefits in the rates of vasospasm, secondary cerebral infarctions, and mortality, without an increased risk of adverse events.

The handgrip test - A historical test for diabetic autonomic neuropathy or a marker of something else?

Cardiovascular autonomic neuropathy (CAN) is a frequent complication of diabetes mellitus and is associated with increased morbidity and mortality in patients with diabetes. Hence, early and correct diagnosis of CAN is crucial. Standard cardiovascular reflex rests (CARTs) have been the gold standard of CAN assessment. Originally, CARTs consisted of five reflex tests, but measuring diastolic blood pressure response to sustained handgrip exercise has no longer been suggested as an established clinical test. Increasing body of evidence suggests that isometric handgrip test should no longer be used for the evaluation of sympathetic dysfunction during cardiovascular autonomic neuropathy assessment in diabetic patients. The associations of isometric handgrip test results with parameters of hypertension and markers of hypertension-related target-organ damage in diabetic and non-diabetic individuals point toward its potential role as a screening tool to identify patients with high cardiovascular risk. The current review summarizes historical view of standard cardiovascular reflex tests and latest data on isometric handgrip test.

Management of Cholinergic Rebound After Abrupt Withdrawal of Clozapine: A Case Report and Systematic Literature Review.

BACKGROUND: Cholinergic discontinuation symptoms, also known as "cholinergic rebound," from abrupt clozapine discontinuation are characterized by a range of somatic and psychiatric symptoms. OBJECTIVE: The objective of this study was to describe the clinical features and management options for clozapine withdrawal-associated cholinergic rebound syndrome (henceforth referred to as CWCRS) and present an illustrative case report. METHODS: Based on a literature search of the databases PubMed, OVID Medline, and Embase as well as reviewing reference lists of relevant past reviews, we carried out a systematic review of case reports on the management of CWCRS from 1946 to 2023. RESULTS: We identified 10 previously published articles on the clinical management of CWCRS, with a total of 18 patients (6 female, 12 male) with an average age of 43 years (standard deviation 14). Half of the patients had a history of tardive dyskinesia. The mean dose of clozapine before discontinuation was 351 mg/day, with duration of clozapine treatment ranging from 3 weeks to 9 years. Clozapine was the most effective treatment, followed by benztropine. CONCLUSIONS: Given the small number of cases and the nonexperimental nature of the available studies, this review could not provide reliable data to guide management of CWCRS. The findings, however, suggest that clozapine may be more effective than other commonly used treatment options. With the high rates of discontinuation among patients on clozapine, there is a pressing need for further research into the epidemiology, natural history, and management of clozapine withdrawal syndromes.

Treatment of postprandial hypotension with acarbose in an adult with cervical spinal cord injury: a case report.

INTRODUCTION: Postprandial hypotension is a type of autonomic dysfunction where there is a decrease in systolic blood pressure of >20 mm HG within 2 h after eating thought to be due to poor cardiovascular compensation for splanchnic blood pooling that occurs with meals. This form of autonomic dysfunction is underdiagnosed in patients with spinal cord injury, likely in part because it can be asymptomatic. CASE PRESENTATION: 26-year-old with complete cervical spinal cord injury (SCI) presented with neck pain described as severe 10/10 pain, which felt like "a rope around his neck." Pain came on during and after meals and was associated with a feeling of pressure behind his eyes, white spots in his vision along with feeling as if he was going to pass out. The caregiver noted a systolic blood pressure drop by about 30-40 points with meals and lost weight due to avoiding eating. A diagnosis of post-prandial hypotension (PPH) was made and Acarbose was started at a low dose 25 mg three times per day with meals. During follow up, the patient reported complete resolution of drops of blood pressure, neck pain, and all associated symptoms. The patient was able to eat comfortably and gained weight. DISCUSSION: There are few case reports on PPH in SCI and none looking at acarbose on a young, nondiabetic person with SCI. Clinicians should be aware that PPH can occur in young otherwise healthy people with SCI. Further research is needed on PPH, including the use of acarbose, in the SCI population.

[Progress on the mechanism and treatment of Parkinson's disease-related pathological pain].

Parkinson's disease (PD) is a common neurodegenerative disease characterized by motor symptoms, including bradykinesia, resting tremor, and progressive rigidity. More recently, non-motor symptoms of PD, such as pain, depression and anxiety, and autonomic dysfunction, have attracted increasing attention from scientists and clinicians. As one of non-motor symptoms, pain has high prevalence and early onset feature. Because the mechanism of PD-related pathological pain is unclear, the clinical therapy for treating PD-related pathological pain is very limited, with a focus on relieving the symptoms. This paper reviewed the clinical features, pathogenesis, and therapeutic strategies of PD-related pathological pain and discussed the mechanism of the chronicity of PD-related pathological pain, hoping to provide useful data for the study of drugs and clinical intervention for PD-related pathological pain.

[Rehabilitation after Spinal Cord Injury : Current trends and principles]. / Rehabilitation nach einer Querschnittlähmung : Aktuelle Trends und Grundlagen.

Traumatic and non traumatic spinal cord injury are rare and an orphan disease in comparison to common diseases. Those affected represent a very special patient population in the treatment even at the site of the accident and in emergency medicine and require a high level of professional expertise. The rehabilitation with the complexity of a spinal cord injury can only succeed with a multiprofessional team that is less focused on the often similar diagnoses according to the International Classification of Diseases (ICD) but on functional disorders and associated activity impairments. Only then the best possible integration and participation/inclusion in sociocultural and professional life can be achieved. In addition to the importance of classical physiotherapy and occupational therapy, this article highlights important but often missing team players, such as neurourology and electrical stimulation. In addition, the problems of frequent and some less recognized complications, such as autonomic dysfunction and the benefits of airway management are highlighted. For a comprehensive overview of rehabilitation in spinal cord injury, reference textbooks and guidelines are recommended that are cited in the text.

[Association of Pathological Progression of Parkinson's Disease and the Thyroid Gland].

Various neurological disturbances in mental status, cognitive function, emotion, and motor function are observed owing to hypo- or hyperthyroidism. Although excretion of thyroid hormones is tightly regulated by the hypothalamus-pituitary gland-thyroid axis, it is partly influenced by blood flow regulated by the postsynaptic sympathetic fibers. In patients with Parkinson's disease in early stages, previous studies using cardiac MIBG scintigraphy or fluorodopa positron emission tomography showed mild-to-moderate denervation of the thyroid. However, whether the autonomic denervation of the thyroid may influence its excretion function, potentially leading to systemic metabolic changes originating from other organs, remains unclear. In this context, we examined the association of thyroid function with Parkinson's disease focusing on the autonomic nervous system referring to our latest achievement. Cardiac MIBG scintigraphy identified decreased uptake of the thyroid especially in early stages of Parkinson's disease with constipation, implying systemic autonomic denervation. Using multiomics analyses, we identified that the autonomic denervation-hypothyroidism-liver axis presented with insufficient fatty acid ß-oxidation in patients with de novo Parkinson's disease.

Urinary epidermal growth factor levels correlate with cardiovascular autonomic neuropathy indices in adults with type 1 diabetes.

The relationship between urinary endothelial growth factor (uEGF) and cardiovascular autonomic neuropathy (CAN) in adults with type 1 diabetes was evaluated. uEGF levels at baseline and standardized CAN measures were collected at baseline and annually for 3 years for type 1 diabetes adults. Linear regression analysis and linear mixed effects model were used for analysis. In this cohort (n = 44, 59% women, mean ± standard deviation age 34 ± 13 years and diabetes duration 14 ± 6 years), lower baseline uEGF levels correlated with lower baseline expiration : inspiration ratios (P = 0.03) and greater annual declines in Valsalva ratios (P = 0.02) in the unadjusted model, and correlated with lower low-frequency power : high-frequency power ratios (P = 0.01) and greater annual changes in low-frequency power : high-frequency power ratios (P = 0.01) after adjustment for age, sex, body mass index, and hemoglobin A1C. In conclusion, baseline uEGF levels correlate to baseline and longitudinal changes in CAN indices. A large-scale, long-term study is needed to validate uEGF as a reliable CAN biomarker.

Recurrent syncope secondary to autonomic dysfunction in spinal cord injury: a case report.

High-level spinal cord injuries are often associated with autonomic impairment, which can result in orthostatic hypotension and syncope. Persistent autonomic dysfunction can manifest with disabling symptoms including recurrent syncopal events. We describe a case of autonomic failure resulting in recurrent syncopal events in a tetraplegic 66-year-old man.

A narrative review of the mechanisms and consequences of intermittent hypoxia and the role of advanced analytic techniques in pediatric autonomic disorders.

Disorders of autonomic functions are typically characterized by disturbances in multiple organ systems. These disturbances are often comorbidities of common and rare diseases, such as epilepsy, sleep apnea, Rett syndrome, congenital heart disease or mitochondrial diseases. Characteristic of many autonomic disorders is the association with intermittent hypoxia and oxidative stress, which can cause or exaggerate a variety of other autonomic dysfunctions, making the treatment and management of these syndromes very complex. In this review we discuss the cellular mechanisms by which intermittent hypoxia can trigger a cascade of molecular, cellular and network events that result in the dysregulation of multiple organ systems. We also describe the importance of computational approaches, artificial intelligence and the analysis of big data to better characterize and recognize the interconnectedness of the various autonomic and non-autonomic symptoms. These techniques can lead to a better understanding of the progression of autonomic disorders, ultimately resulting in better care and management.

Refractory bradycardia and hypotension in patients with autonomic dysfunction treated with pseudoephedrine.

We describe a man in his 40s with a history of chronic intranasal cocaine use and C5-C7 incomplete quadriplegia complicated by neurogenic orthostatic hypotension, admitted to the intensive care unit for worsening bradycardia and hypotension requiring initiation of dopamine and an increase of his home midodrine dose. The patient experienced refractory bradycardia and hypotension with weaning of dopamine, and therefore a recommendation was made to add pseudoephedrine to his current regimen. This case describes the addition of pseudoephedrine to facilitate weaning off intravenous vasopressors within 24 hours in a patient with refractory bradycardia and hypotension secondary to autonomic dysfunction.

Harlequin syndrome.

A 56-year-old man presented to the clinic with episodic headaches for several years which had been worsening over a few months prior to the presentation. He described headache as sharp, stabbing pain around the left eye associated with nausea, vomiting, photophobia, and phonophobia lasting for hours associated with flushing on the left side of the face. The picture of his face during these episodes showed flushing of the left side of the face, ptosis of the right eyelid, and miosis (panel A). Flushing in his face would resolve with the abortion of the headache. At the time of presentation to the clinic, his neurological exam was only significant for mild left eye ptosis and miosis (panels B and C). Extensive workup including MRI brain, cervical spine, thoracic spine, lumbar spine, CTA head and neck, and CT maxillofacial was unremarkable. He had tried several medications in the past including valproic acid, nortriptyline, and verapamil without significant benefit. He was started on erenumab for migraine prophylaxis and was given sumatriptan for abortive therapy following which his headaches improved. The patient was diagnosed with idiopathic left Horner's syndrome and his migraines with autonomic dysfunction would present with unilateral flushing opposite to the site of Horner's presenting as Harlequin syndrome [1, 2].

Sleep disordered breathing improvement prevents worsening of autonomic dysfunction in children with Down syndrome.

BACKGROUND: Resolution of sleep disordered breathing (SDB) in typically developing children normalises heart rate variability (HRV), a measure of autonomic control, to that of non-snoring controls. Children with Down Syndrome (DS) have dampened heart rate variability (HRV) but the effect of treatment is not known. To assess the effect of improvement of SDB on autonomic control we compared HRV in children with DS whose SDB improved over 2 y, to those whose SDB did not improve. METHODS: 24 children (3-19 y) had a baseline and follow-up polysomnographic study 2 y later. Improved SDB was defined as a reduction in obstructive apnea hypopnea index (OAHI) to ≤ 50% of baseline. Children were grouped into Improved (n = 12) and Unimproved (n = 12). Power spectral analysis of the ECG determined low frequency (LF), high frequency (HF) power and the LF/HF ratio. Seven children in the Improved and 2 in the Unimproved group were treated following the baseline study. RESULTS: In the Unimproved group at follow-up, LF power was lower compared to baseline during N3 and Total Sleep (p < 0.05 for both). HF power was lower during REM (p < 0.05). HRV remained unchanged between studies in the Improved group. CONCLUSION: Autonomic control worsened as indicated by lower LF and HF power in children whose SDB was not improved. In contrast, in those children with improved SDB, autonomic control remained the same, suggesting improvement in SDB severity prevents further worsening of autonomic control in children with DS.

[Motor and autonomic disorders influence on pain syndrome of patients with Parkinson's disease of the I-III H&Y stages]. / Vliyanie motornykh i vegetativnykh narushenii na vyrazhennost' bolevogo sindroma u patsientov s I­III stadiyami bolezni Parkinsona.

OBJECTIVE: To evaluate the influence of motor and autonomic disorders on the pain of patients with PD of the I-III H&Y stages and possibility of correcting the pain with dopamine receptor agonists (ADR). MATERIAL AND METHODS: 252 patients (128 women and 124 men, 42-80 years old) with PD of I-III Hoehn and Yahr stages (H&Y) were examined using the following scales: UPDRS, daily activity Sch&En, quality of life PDQ-39, MMSE, BDI, PFS-16, NMSQuest, GSRS, AUA; 53 patients were piribedil treated during 6 months. RESULTS: Our results indicated a wide prevalence of pain syndrome in PD patients (58.6%), starting from the early stages (50% for the Ist stage). The most stable pain associations were found with the PD stage, levodopa doses, severity of motor symptoms (postural disorders and hypokinesia manifestations) and motor complications («off-periods¼ and dyskinesias), as well as non-motor PD manifestations depression and autonomic dysfunctions (constipation, swallowing disorders, and frequent urination). The regression analysis showed, that the severity of motor complications and depression were the predictors of pain occurrence. The pain syndrome in patients with PD of I-III stages underwent significant regression (by 51% and 62%, after 1.5 and 6 months of therapy, respectively) after ADR (piribedil) addition to their therapy; it's probably due to improving the motor component and decreasing depressive disorders. CONCLUSIONS: The piribedil inclusion contributes to the reduction of pain syndrome, regardless is it used in monotherapy or in conjunction with levodopa preparations.