Severe Orthostatic Hypotension Research Articles

Anti-IgLON5 disease as a differential diagnosis of multiple system atrophy

IntroductionAnti-immunoglobulin-like cell adhesion molecule 5 (IgLON5) disease is a rare autoimmune encephalitis that can mimic progressive supranuclear palsy or corticobasal syndrome. Moreover, anti-IgLON5 disease can present with symptoms characteristic of multiple system atrophy (MSA), such as cerebellar ataxia and autonomic dysfunction. However, the clinical features of anti-IgLON5 disease resembling MSA have not been well established. MethodsWe enrolled 35 patients with suspected MSA for whom anti-IgLON5 antibody tests were requested. We evaluated immunoglobulin G (IgG) against IgLON5 using cell-based assays. We also summarized the clinical characteristics of patients who were positive for anti-IgLON5 antibodies. ResultsWe identified serum and cerebrospinal fluid anti-IgLON5 antibodies in three patients. These patients had many clinical features characteristic of MSA, including parkinsonism, cerebellar ataxia, severe orthostatic hypotension, acute respiratory failure, sleep parasomnia, vocal cord paralysis, and pyramidal tract signs. Clinical features atypical for MSA were myorhythmia, horizontal eye movement restriction, fasciculations, and painful muscle cramps. ConclusionAnti-IgLON5 disease may be an important differential diagnosis of MSA. A comprehensive physical examination, including assessments of eye movement, lower motor neuron signs, and atypical involuntary movements, is important to avoid misdiagnosis.

Sex-related differences in the clinical presentation of multiple system atrophy

PurposeTo investigate sex-related differences in the clinical presentation of multiple system atrophy (MSA) through a literature review and an analysis of a retrospective cohort.MethodsThe PubMed database was searched for articles including sex-related information in MSA. In a retrospective Innsbruck cohort, we investigated the baseline to last available follow-up clinical-demographic differences between men and women with MSA in a univariate fashion, followed by multivariable binary regression analysis.ResultsThe literature search yielded 46 publications with sex-related information in MSA. Most studies found comparable survival rates between the sexes, while some recent reports suggested a potential survival benefit for women, possibly due to initial motor onset and overall less severe autonomic failure compared to men. The retrospective Innsbruck MSA cohort comprised 56 female and 60 male individuals with a comparable median follow-up of 27 months. At baseline, female sex was independently associated with depression (odds ratio [OR] 4.7; p = 0.007) and male sex with severe orthostatic hypotension (OR 5.5; p = 0.016). In addition, at last follow-up, female sex was associated with the intake of central nervous system-active drugs (OR 4.1; p = 0.029), whereas male sex was associated with the presence of supine hypertension (OR 3.0; p = 0.020) and the intake of antihypertensive medications (OR 8.7; p = 0.001). Male sex was also associated with initiation of antihypertensive medications over the observation period (OR 12.4; p = 0.004).ConclusionThe available literature and findings of the present study indicate sex-related differences in the clinical presentation of MSA and its evolution over time, highlighting the importance of considering sex in symptom exploration, therapeutic decision-making, and future clinical trial design.

Aberrant microstructural integrity of white matter in mild and severe orthostatic hypotension: A NODDI study.

Scarce evidence is available to elucidate the association between the abnormal microstructure of white matter (WM) and cognitive performance in patients with orthostatic hypotension (OH). This study investigated the microstructural integrity of WM in patients with mild OH (MOH) and severe OH (SOH) and evaluated the association of abnormal WM microstructure with the broad cognitive domains and cognition-related plasma biomarkers. Our study included 72 non-OH (NOH), 17 MOH, and 11 SOH participants. Across the groups, the WM integrity was analyzed by neurite orientation dispersion and density imaging (NODDI), and differences in WM microstructure were evaluated by nonparametric tests and post hoc models. The correlations between WM microstructure and broad cognitive domains and cognition-related plasma biomarkers were assessed by Spearman's correlation analysis. The abnormal WM microstructure was localized to the WM fiber bundles in MOH patients but distributed widely in SOH cohorts (p < 0.05). Further analysis showed that the neurite density index of the left cingulate gyrus was negatively associated with amyloid β-40, glial fibrillary acidic protein, neurofilament light chain, phospho-tau181 (p < 0.05) but positively with global cognitive function (MOCA, MMSE, AER-III), memory, attention, language, language fluency, visuospatial function and amyloid β-40 / amyloid β-42 (p < 0.05). Additionally, other abnormal WM microstructures of OH were associated with broad cognitive domains and cognition-related plasma biomarkers to varying degrees. The findings evidence that abnormal WM microstructures may present themselves as early as in the MOH phase and that these structural abnormalities are associated with cognitive functions and cognition-related plasma biomarkers.

Evaluation of Clozapine-induced Toxicities in Psychic Patients in Mental Health Care Hospitals in the Southern Region of the Saudi Arabia Kingdom

Background:: Clozapine is a psychiatric medication that may cause various side effects, some of them may be serious and fatal adverse effects, such as severe neutropenia, agranulocytosis, lymphocytopenia, myocarditis, and orthostatic hypotension, that have been associated to an increased risk of death. Objective:: This study aimed to evaluate the serious and potentially fatal adverse effects of clozapine toxicity in psychic patients at mental health care hospitals in the Southern region of the Kingdom of Saudi Arabia. Methods:: By using a survey, data were retrospectively collected from 193 adult psychic patient reports who have been administrated clozapine with regular follow-ups, in mental health hospitals in the Southern region of Saudi Arabia between 2019 and 2021. Then, these data are recorded and analyzed Statistically using SPSS software, with suitable tests, and predetermined statistical significance (p-value) of less than 0.001. Results:: The occurrence of agranulocytosis, neutropenia, hypotension, and seizures showed a highly significant correlation with higher doses of clozapine administration (i.e. p&lt;0.001). Similarly, agranulocytosis and neutropenia were significantly associated with the occurrence of both hypotension and seizures (i.e. p&lt;0.001). Conclusion:: The collected data in this study showed an increased incidence of agranulocytosis and neutropenia associated with clozapine-treated psychic patients in the Southern region of the Kingdom of Saudi Arabia which warrants further clinical studies to find this correlation.

FRI218 Von Hippel-Lindau With Pheochromocytoma And Severe Orthostatic Hypotension

Abstract Disclosure: N. Ebrahimi: None. C.G. Rivas Pajuelo: None. R. Habibi: None. S. Tariq: None. S.A. Penquite: None. Introduction: Von Hippel-Lindau (VHL) syndrome clinically manifests with benign and malignant tumors across multiple organ systems including the cerebellum, retina, kidney, and adrenal glands. Pheochromocytoma occurs in 25-30% of patients with VHL. Up to 50% of patients with pheochromocytoma present with hypertension or paroxysmal hypertension, although patients can be normotensive on presentation. Patients with pheochromocytoma are often severely volume depleted due to chronic vasoconstriction. Here we present a case of VHL with pheochromocytoma complicated by profound orthostatic hypotension after initiation of alpha-blockade. Case Presentation: A 32-year-old man presented for evaluation of progressive headache and diplopia. Patient was normotensive on initial presentation with BP 129/80mmHg. Brain MRI with contrast subsequently revealed a posterior fossa cystic mass with an avidly enhancing central nodule concerning for hemangioblastoma. Given these findings, a CT chest/abdomen/pelvis was obtained, which demonstrated a 4.6 x 5.0 cm right adrenal mass, several enhancing renal lesions, and multiple cystic lesions throughout the pancreas. This constellation of radiological findings was clinically concerning for VHL. Further endocrinologic work-up revealed plasma metanephrines 663 pg/mL (insert reference range here), plasma catecholamines 770 pg/mL (insert reference range here), which confirmed the diagnosis of pheochromocytoma. Alpha blockade was initiated with doxazosin 4 mg BID, and a high sodium diet (insert g/day). Shortly after initiation of doxazosin, patient developed severe orthostatic hypotension despite salt loading and volume resuscitation. Ultimately doxazosin was discontinued, and surgery was postponed due to severe symptomatic orthostatic hypotension limiting patient’s ability to get out of bed. High sodium diet was continued on hospital discharge and alpha-adrenergic blockade was later re-initiated which patient is tolerating well. Patient is pending adrenalectomy in the coming weeks. Discussion: Orthostatic hypotension in pheochromocytoma is expected due to volume depletion from chronic vasoconstriction. Alpha adrenergic blockade is required to alleviate hypertension, allow for adequate volume expansion, and to prevent a hypertensive crisis intraoperatively. Clinicians should be aware of the commercially available alpha-adrenergic antagonists and when they should be temporarily discontinued. There is no preferred alpha-adrenergic antagonist agent, however doxazosin has shown to cause less orthostatic hypotension and does not have such an antihypertensive effect as of Phenoxybenzamine. Presentation: Friday, June 16, 2023

Early-onset hereditary isolated non-neurogenic orthostatic hypotension in a Swedish family

PurposeOrthostatic hypotension is a common condition with heterogeneous and, in many cases, unclear underlying pathophysiology. Frequent symptoms are syncope and falls with a strong impact on daily life. A two-generation family with eight individuals segregating early-onset severe orthostatic hypotension with persistent tachycardia in upright position and repeated faints was identified. Our aim was to elucidate the underlying pathophysiology.MethodsOne severely affected individual underwent thorough investigation with neurophysiological and blood pressure (BP) measurements, including direct recording of baroreflex-governed sympathetic nerve signalling and induction of BP rise with phenylephrine. Family members underwent parts of the examination. Genetic analysis using exome sequencing was performed.ResultsMarked postural hypotension with greatly reduced cardiac preload was observed, but without signs of autonomic nervous system dysfunction: sympathetic nerve signalling was normal, as were catecholamine levels, and phenylephrine stimulation revealed a normal increase in BP. The results of the genetic analysis using exome sequencing comprising all known genes associated with the regulation of BP and catecholamine metabolism were normal.ConclusionThe combined findings suggest an autosomal dominant form of early-onset orthostatic hypotension with variable clinical expression and without any additional autonomic dysfunction. It is possible that further investigation will reveal an as yet undescribed entity of orthostatic hypotension transmitted as an autosomal dominant trait.

Paravertebral Cerebrospinal Fluid Exudation in Young Women with Postdural Puncture Headache: A Hypothetical Interpretation based on Anatomical Study on Intervertebral Foramen.

Background Postdural puncture headache (PDPH) is defined as a prolonged orthostatic headache secondary to a lumbar puncture. The mechanism underlying this unpleasant complication and the reasons explaining its higher incidence in the young are not well understood. Here, we speculate on the mechanisms underlying PDPH based on spinal magnetic resonance imaging (MRI) in patients with PDPH and an anatomical study on the size of the intervertebral foramen. Methods Brain and spinal MRI findings were examined in two young women with PDPH. The relationship between age and size of the intervertebral foramen on computed tomography was assessed in 25 female volunteers (22-89 years old) without spinal disease. Results The causative interventions leading to PDPH were epidural anesthesia for painless delivery in a 28-year-old woman and lumbar puncture for examination of the cerebrospinal fluid (CSF) in a 17-year-old woman. These two patients developed severe orthostatic hypotension following the procedure. Brain MRI showed signs of intracranial hypotension, including subdural effusion, in one patient, but no abnormality in the other. Spinal MRI revealed an anterior shift of the spinal cord at the thoracic level and CSF exudation into the paravertebral space at the lumbar level. Treatment involving an epidural blood patch in one patient and strict bed rest with sufficient hydration in the second led to improvement of symptoms and reduction of paravertebral CSF exudation. The size of the intervertebral foramen at the L2-3 level in the 25 volunteers showed a decrease in an age-dependent manner (Spearman's rho -0.8751, p < 0.001). Conclusion We suggest that CSF exudation from the epidural space of the vertebral canal to the paravertebral space through the intervertebral foramen, which is generally larger in the younger population, is the causative mechanism of PDPH.

Transcutaneous Spinal Cord Stimulation Attenuates Blood Pressure Drops in Orthostasis.

Orthostatic hypotension is a complex medical problem with various underlying pathogenic mechanisms and limited modalities for its correction. Since transcutaneous spinal cord stimulation (t-SCS) leads to immediate blood pressure (BP) elevation in a supine position, we suggested that t-SCS may attenuate blood pressure drops in orthostasis. We aimed to evaluate the hemodynamic effects of t-SCS during tilt testing in a feasibility study in three patients with documented orthostatic hypotension. Four sessions on two different days of tilt testing on and off t-SCS were performed on each patient. While tilting with t-SCS off showed typical significant BP drops in every patient, active t-SCS resulted in systemic vascular resistance (SVR) elevation in all patients and significantly higher values of systolic and diastolic BP in two patients. T-SCS requires further investigation on a larger patient population. However, our preliminary results demonstrate its ability for SVR and BP elevation in subjects with severe orthostatic hypotension.

Diabetes-Induced Cardiac Autonomic Neuropathy: Impact on Heart Function and Prognosis.

Cardiovascular autonomic neuropathy (CAN) is a severe complication of the advance stage of diabetes. More than 50% of diabetic patients diagnosed with peripheral neuropathy will have CAN, with clinical manifestations including tachycardia, severe orthostatic hypotension, syncope, and physical exercise intolerance. Since the prevalence of diabetes is increasing, a concomitant increase in CAN is expected and will reduce quality of life and increase mortality. Autonomic dysfunction is associated with reduced baroreflex sensitivity and impairment of sympathetic and parasympathetic modulation. Various autonomic function tests are used to diagnose CAN, a condition without adequate treatment. It is important to consider the control of glucose level and blood pressure as key factors for preventing CAN progression. However, altered biomarkers of inflammatory and endothelial function, increased purinergic receptor expression, and exacerbated oxidative stress lead to possible targets for the treatment of CAN. The present review describes the molecular alterations seen in CAN, diagnosis, and possible alternative treatments.

Hypotensive unawareness in Parkinson's disease-related autonomic dysfunction.

This case demonstrates how orthostatic hypotension in the absence of typical symptoms of light-headedness/dizziness when changing posture, can contribute to the burden of falls in Parkinson's disease. At least one-third of people with severe orthostatic hypotension do not report typical symptoms, and this figure appears to be higher in patients with Parkinson's disease. This is important clinically as it can increase the difficulty in ascribing falls to orthostatic hypotension, especially given the other competing reasons in Parkinson's disease and orthostatic hypotension symptoms can act as a prompt for the patient to act to prevent falls-related injuries. There is a clinical requirement, therefore, to screen for and manage orthostatic hypotension in patients with Parkinson's disease to prevent falls, even in those who do not report typical symptoms.

ODP291 A Series of COVID Reinfections in a Vaccinated Patient leading to Development of Neurogenic Orthostatic Hypotension and Postural Orthostatic Tachycardia

Abstract The recently recognized 'long COVID' syndrome, encompasses symptoms of shortness of breath, chest pain, palpitations and orthostatic intolerance which can last for weeks or more following even mild illness. 'Long COVID' is postulated to be related to a virus- or immune-mediated disruption of the autonomic nervous system resulting in orthostatic intolerance syndromes. We report a 32-yr old female nurse who presented to the endocrinology clinic for symptoms of orthostatic hypotension following two COVID 19 infections. She had received 1 dose of Moderna vaccine in February and March of 2021 respectively. She was hospitalized for COVID June and September of 2021. Following the first hospitalization, she developed severe orthostatic hypotension, chest pain, shortness of breath, fatigue, anxiety, memory, concentration and word finding difficulty. Blood pressure ranged from 110/78 to 124/82 while lying and from 85/45 to 103/59 while standing. HR ranged from 88 to 96 while lying and from 130 to 42 while standing. She was started on midodrine 10 mg three times daily which was discontinued due to patient intolerance. She followed a regimen of adequate hydration, adequate salt intake, fall precautions, physical and speech therapy and high protein/low carb diet with frequent snacks, which improved her symptoms of dizziness and orthostasis, but without complete resolution. However, symptoms of anxiety, dizziness, chest pain and palpitations became even worse after the second hospitalization. She was started on Propranolol 20 mg 2-3 times daily depending on symptoms, and she felt better with this intervention. Evaluation for secondary causes of hypotension were all negative [Cortisol of 19 ug/dL (n=5.3-22.5); ACTH 20 pg/mL (n=0-47); TSH 2.36 uIU/mL (n=0.358 -3.74); Free T4 0.97 ng/dL (n=0.76-1.46); B12 480 pg/mL (n=193-986); Hba1c 4.9%; 25 OH Vitamin D 24.3 ng/mL; tryptase 3.7 mcg/L (n= &amp;lt;11); Sed rate 4 mm/HR (n=0-20). CBC, CMP, TPO and Tg abs, troponin levels, iron studies, ANA panel, Rheumatoid factor, anti-CCP abs, myasthenia gravis panel], CT head and MRI brain, EKG and QTc interval. Echocardiogram= small PFO. 'Post-acute COVID' refers to persistent symptoms 3 weeks after COVID-19 infection, while 'Chronic COVID' describes symptoms lasting more than 12 weeks. Symptoms include fatigue, dyspnea, chest pain, palpitations, dizziness, body aches, presyncope and orthostatic intolerance. Individuals may even develop post-traumatic stress disorder, panic attacks and irritable bowel syndrome. Orthostatic intolerance occurs due to release of epinephrine and norepinephrine leading to development of palpitations, breathlessness, and chest pain. It has been well described that orthostatic intolerance is preceded by viral infections and is associated with the development of autoantibodies α-/β-adrenoceptors and muscarinic receptors. COVID 19 itself can affect the autonomic nervous system through the release of a cytokine storm leading to sympathetic activation. It is crucial to consider the diagnosis of orthostatic intolerance syndromes post COVID infection. Presentation: No date and time listed

ORTHOSTATIC HYPOTENSION IN COVID 19 – CATCH IT IF YOU CAN!

Objective: The relationship between COVID-19 and blood pressure (BP) has raised great concern since the discovery of Angiotensin Convertase Enzyme 2 (ACE 2) – mediated mechanism of action for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV2). Hypertension (HTN) itself proved to be a risk factor for more severe Coronavirus Disease 19 (COVID -19). However less studies focus on the trend of blood BP for patients with COVID-19 during the initial phase of disease. Design and method: We present the case of a 71 years old woman with grade 2 HTN previously controlled with diuretic and betablocker therapy that came to our hospital with dyspnea, cough and debilitating fatigue progressively worsened in the last 10 days. The patient also related the first episode of syncope in her life the night before the presentation. Results: The clinical evaluation revealed a conscious, euvolemic, with polypnea and a peripheral saturation in oxygen of 86%, corrected to 95% with 9 liters oxygen/minute via simple face mask and a BP of 110/70 mmHg with a ventricular rate of 45 beats per minute in supine position. The assessment of BP values while standing showed a value of 78/60 mmHg after 1 minute and 58/40 mmHg after 3 minutes, while the ventricular rate increased overall to 65 beats per minute. ECG was remarkable only for mild bradycardia and computed tomography pulmonary angiogram excluded pulmonary embolism. The patient was admitted with severe COVID-19 accompanied by severe orthostatic hypotension and bradycardia. Continuous telemonitoring showed only mild bradycardia. Under standard COVID 19 treatment, after 10 days, her symptoms had resolved with no residual orthostatic hypotension or bradycardia. Conclusions: In conclusion this case reflects the life-threatening dysautonomia caused by SARS-COV 2 infection. More concern should be placed on this type of fragile patients, taking into account both the macroscopic implications of being confined to bed for a long period of time and the microscopic butterfly effect caused by the binding of the virus on the widespread ACE 2 in the lungs, heart, kidneys and digestive tract.

Droxidopa for Treatment of Refractory Orthostatic Hypotension in Patients with AL Amyloidosis: A Case Series

BackgroundOrthostatic hypotension due to autonomic dysfunction is a well-known complication of light chain (AL) amyloidosis, which can become progressively debilitating and difficult to manage. Treatment of the underlying plasma cell dyscrasia will eventually decrease further amyloid deposition. Management of orthostatic hypotension secondary to AL amyloidosis improves quality of life and facilitates delivery of plasma cell therapy. Pharmacologic interventions include fludrocortisone, sympathomimetic agents such as midodrine, droxidopa, the acetylcholinesterase inhibitor pyridostigmine or the norepinephrine transporter (NET) inhibitor atomoxetine. Fludrocortisone is often poorly tolerated in amyloid patients because it may exacerbate edema. Droxidopa is a synthetic amino acid analog that is directly metabolized to norepinephrine by dopa-decarboxylase, which increases blood pressure (BP) by inducing peripheral arterial and venous vasoconstriction.AimsTo assess the effectiveness of droxidopa in patients with AL amyloidosis with severe orthostatic hypotension refractory to midodrine. Also, to describe effective dose of droxidopa, duration of therapy, adverse effects and reasons for discontinuation.MethodsA regional retrospective study was done in patients with AL amyloidosis with severe, refractory orthostatic hypotension who received droxidopa. Retrospective data was reviewed from 2018 to 2021 at a single academic center in the United States.ResultsFive patients with AL amyloidosis were included in the study; three patients had lambda-restricted plasma cell dyscrasia and two had multiple myeloma (MM) associated AL amyloidosis (both kappa light chain restricted). Of the five patients, all had cardiac, renal, autonomic nervous system and peripheral nervous system involvement and two of the five had gastrointestinal involvement as well. Given their poor performance status and advanced organ involvement, none of the patients were eligible for high-dose intravenous melphalan with autologous peripheral blood stem cell transplantation (HDM/SCT), and thus were treated with cyclophosphamide, bortezomib and dexamethasone (CyBorD). All patients achieved very good partial response to complete hematologic response. The main findings are summarized in table 1.All patients had severe, symptomatic orthostatic hypotension that was objectively defined as a decrease in systolic blood pressure by 20 millimeters of mercury (mmHg) or a decrease in diastolic blood pressure of 10 mmHg from supine to either sitting or standing in the clinic or at home (Freeman R consensus statement on the definition of orthostatic hypotension, 2011). Initial treatment for all patients included midodrine, ranging from 5 to 30mg TID based on individual tolerance. Three of the patients also were initially treated with fludrocortisone 0.05 to 0.2mg daily (use limited by fluid retention). Only one patient was on pyridostigmine 30mg TID (case 5). Given persistence of symptoms despite therapy, droxidopa was started at 100mg TID in all patients, and the dose was titrated as tolerated. None required the maximal approved dose of 600mg TID.The indication to start droxidopa was based on refractory, symptomatic orthostatic hypotension in all five patients. After initiation of droxidopa, all except for one patient reported improvement both in symptoms of lightheadedness as well as measurements of orthostatic blood pressure values. By the end of this study, three patients continued treatment with droxidopa (cases 1-3); one was weaned-off after resolution of symptoms (case 5) and one was discontinued due to supine hypertension (case 4).ConclusionData shows that droxidopa is an effective treatment of orthostatic hypotension refractory to midodrine in patients with AL amyloidosis. Slow titration may be important to minimize rapid changes in blood pressure. Further studies are warranted to assess droxidopa's safety and compare with other treatments for orthostatic hypotension. [Display omitted] DisclosuresHughes: Amgen: Speakers Bureau; Rigel: Other: Advisory Board, Research Funding; Abbvie: Speakers Bureau; Karyopharm: Other: Advisory Board, Speakers Bureau. Sanchorawala: Celgene: Research Funding; Takeda: Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Prothena: Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees; Caelum: Membership on an entity's Board of Directors or advisory committees, Research Funding; Regeneron: Membership on an entity's Board of Directors or advisory committees; Proclara: Membership on an entity's Board of Directors or advisory committees; Oncopeptide: Research Funding; Karyopharm: Research Funding; Sorrento: Research Funding; Pfizer: Honoraria. Sloan: Nuvectis: Consultancy; Abbvie: Consultancy; Stemline: Consultancy; Astrazeneca: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Pharmacosmos: Membership on an entity's Board of Directors or advisory committees.

M151 A RARE CASE OF AUTOIMMUNE AUTONOMIC GANGLIONOPATHY

Autoimmune autonomic ganglionopathy (AAG) is a rare disease mediated by antibodies causing severe orthostatic-hypotension. Due to its unique presentation, patients can go undiagnosed causing them profound disability and poor-quality of life. Our case of AAG presenting in a 69-year-old-female illustrates the importance of including AAG in the differential diagnosis for patients who present with autonomic dysfunction.

A case of severe orthostatic hypotension induced by vitamin B12 deficiency

A case of severe orthostatic hypotension induced by vitamin B12 deficiency

Severe orthostatic hypotension in otherwise uncomplicated Plasmodium vivax infection

Impaired autonomic control of postural homeostasis resulting in orthostatic hypotension has been described in falciparum malaria. However, severe orthostatic intolerance in Plasmodium vivax has been rarely reported. A case of non-immune previously healthy Thai woman presenting with P. vivax infection with well-documented orthostatic hypotension is described. In addition to oral chloroquine and intravenous artesunate, the patient was treated with fluid resuscitation and norepinephrine. During hospitalization, her haemodynamic profile revealed orthostatic hypotension persisting for another three days after microscopic and polymerase chain reaction confirmed parasite clearance. Potential causes are discussed.

Differences in 5-Aminolevulinic Acid-Induced Hemodynamic Changes between Patients Undergoing Neurosurgery and Urological Surgery.

Introduction: Oral 5-aminolevulinic acid (5-ALA) is often used for photodynamic diagnosis-assisted glioma or bladder tumor surgery. 5-ALA affects blood pressure (BP). In fact, hypotension is a well-known adverse effect of 5-ALA in urology. However, information regarding 5-ALA-induced hemodynamic changes in neurosurgery remains limited. Furthermore, the duration of hypotension and how 5-ALA affects the heart rate (HR) are yet to be determined. Thus, in this study, we aimed to elucidate 5-ALA-induced perioperative hemodynamic changes in neurosurgery and urological surgery by examining real-world data. Methods: Consecutive patients who underwent neurosurgery (neurosurgery patients; 5-ALA-pretreated vs. non-pretreated [17 vs. 16], from January 2014 to March 2021) and urological surgery (urological surgery patients; 5-ALA-pretreated vs. non-pretreated [26 vs. 101], from August 2018 to September 2020) were enrolled. Differences in hemodynamics were evaluated using the linear mixed model. BP and HR in 5-ALA-pretreated patients were compared with those in non-pretreated patients. Differences in 5-ALA-induced preoperative BP changes were compared between the neurosurgery patients and urological surgery patients. Results: 5-ALA scarcely affected the hemodynamics in neurosurgery patients, whereas 5-ALA-induced hemodynamic changes were clearly observed in urological surgery patients. Hemodynamic parameters were found to be not significantly different between 5-ALA-pretreated and non-pretreated neurosurgery patients. The preoperative, intraoperative, and postoperative BP in 5-ALA-pretreated urological surgery patients were significantly lower than those in the non-pretreated patients. Preoperatively, two 5-ALA-pretreated urological surgery patients had severe postural hypotension (systolic BP <50 mmHg), and one of them did not continue with the surgery because of prolonged severe hypotension. The BP in 5-ALA-pretreated urological surgery patients tended to be persistently lower for 9 h after 5-ALA pretreatment. The preoperative and postoperative HR values were higher in 5-ALA-pretreated urological surgery patients. Cumulative incidences of BP reduction and HR elevation were significantly higher in 5-ALA-pretreated urological surgery patients. The preoperative BP reduction in 5-ALA-pretreated urological surgery patients was significantly larger than that in neurosurgery patients. Conclusions: 5-ALA-induced hemodynamics may differ between neurosurgery patients and urological surgery patients. 5-ALA may affect BP for at least 9 h.

Severe orthostatic hypotension and weight loss associated with cancer therapy.

Two cases of orthostatic hypotension associated with weight loss following cancer treatment are described. Conventional treatments for orthostatic hypotension proved ineffective. A hypothesis of association with skeletal muscle wasting is discussed.

Assessing the impact of pain-linked Nav1.7 variants: An example of two variants with no biophysical effect

ABSTRACT Mutations in the voltage-gated sodium channel Nav1.7 are linked to human pain. The Nav1.7/N1245S variant was described before in several patients suffering from primary erythromelalgia and/or olfactory hypersensitivity. We have identified this variant in a pain patient and a patient suffering from severe and life-threatening orthostatic hypotension. In addition, we report a female patient suffering from muscle pain and carrying the Nav1.7/E1139K variant. We tested both Nav1.7 variants by whole-cell voltage-clamp recordings in HEK293 cells, revealing a slightly enhanced current density for the N1245S variant when co-expressed with the β1 subunit. This effect was counteracted by an enhanced slow inactivation. Both variants showed similar voltage dependence of activation and steady-state fast inactivation, as well as kinetics of fast inactivation, deactivation, and use-dependency compared to WT Nav1.7. Finally, homology modeling revealed that the N1245S substitution results in different intramolecular interaction partners. Taken together, these experiments do not point to a clear pathogenic effect of either the N1245S or E1139K variant and suggest they may not be solely responsible for the patients’ pain symptoms. As discussed previously for other variants, investigations in heterologous expression systems may not sufficiently mimic the pathophysiological situation in pain patients, and single nucleotide variants in other genes or modulatory proteins are necessary for these specific variants to show their effect. Our findings stress that biophysical investigations of ion channel mutations need to be evaluated with care and should preferably be supplemented with studies investigating the mutations in their context, ideally in human sensory neurons.

Clinical presentation and long-term follow-up of dopamine beta hydroxylase deficiency.

Dopamine beta hydroxylase (DBH) deficiency is an extremely rare autosomal recessive disorder with severe orthostatic hypotension, that can be treated with L‐threo‐3,4‐dihydroxyphenylserine (L‐DOPS). We aimed to summarize clinical, biochemical, and genetic data of all world‐wide reported patients with DBH‐deficiency, and to present detailed new data on long‐term follow‐up of a relatively large Dutch cohort. We retrospectively describe 10 patients from a Dutch cohort and 15 additional patients from the literature. We identified 25 patients (15 females) from 20 families. Ten patients were diagnosed in the Netherlands. Duration of follow‐up of Dutch patients ranged from 1 to 21 years (median 13 years). All patients had severe orthostatic hypotension. Severely decreased or absent (nor)epinephrine, and increased dopamine plasma concentrations were found in 24/25 patients. Impaired kidney function and anemia were present in all Dutch patients, hypomagnesaemia in 5 out of 10. Clinically, all patients responded very well to L‐DOPS, with marked reduction of orthostatic complaints. However, orthostatic hypotension remained present, and kidney function, anemia, and hypomagnesaemia only partially improved. Plasma norepinephrine increased and became detectable, while epinephrine remained undetectable in most patients. We confirm the core clinical characteristics of DBH‐deficiency and the pathognomonic profile of catecholamines in body fluids. Impaired renal function, anemia, and hypomagnesaemia can be part of the clinical presentation. The subjective response to L‐DOPS treatment is excellent and sustained, although the neurotransmitter profile in plasma does not normalize completely. Furthermore, orthostatic hypotension as well as renal function, anemia, and hypomagnesaemia improve only partially.