Severe Orthostatic Hypotension Research Articles

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.

Use of Droxidopa to Treat Orthostatic Hypotension in a Patient With Hfref

Background Orthostatic hypotension in patients with a low ejection fraction has been associated with a very high morbidity and mortality. Some of this is due to co-morbidity and some is due to the inability to use conventional medications such as ACE inhibitors, ARBs, sacubitril/valsartan and beta blockers because of worsening hypotension. Midodrine and Florinef can raise blood pressure, but are limited in their ability to do so and have theoretical disadvantages due to increase in systemic resistance and increase in volume overload, respectively. Droxidopa, a new treatment for orthostatic hypotension due to autonomic failure, is metabolized into norepinephrine and could potentially provide a new treatment modality for these very difficult patients. Case report We treated a 71 -year-old, Caucasian male with chronic atrial fibrillation and non-ischemic cardiomyopathy. Even with a biventricular defibrillator, severe orthostatic hypotension continued resulting in falls and head trauma. He was unable to tolerate any of the conventional medications to try to raise his ejection fraction due to worsening hypotension. Droxidopa was initiated and progressively up titrated, finally reaching a dose of 300 mg t.i.d. At this dose, his blood pressure stabilized and he was able to tolerate the following medications: Sacubitril/valsartan 24/26 b.i.d., metoprolol succinate 25 mg daily. On this medicine combination his blood pressure ranged from 101/58 to 110/65 and his New York Heart Association class improved from class IV to class II. LV ejection fraction was 30% initially and increased to 50% after 4 months of treatment with Droxidopa. He became ambulatory and had a much improved quality of life. Renal function and other laboratory parameters remained stable on the droxidopa. His ICD interrogation showed no evidence of any proarrhythmia affects of droxidopa. Conclusion Droxidopa provides potentially a new treatment modality for patients with low ejection fraction and refractory orthostatic hypotension. Longer term follow up will be needed to confirm efficacy and safety. Rhythm follow up of over 9 months has shown no evidence of proarrhythmia. Additional patients and longer term follow up results are in preparation, but have had similar benefits to date.

Orthostatic Hemodynamic Changes in Brain Damage

Aim: to study orthostatic hemodynamic changes in patients with chronic disorders of consciousness after critical brain damage.Materials and methods. We studied 30 patients (10 women and 20 men) with chronic disorders of consciousness after severe brain damage aged 45±7 years, 10 of which were in the vegetative state (VS) and 20 had the minimally conscious state (MCS). The main causes of brain damage were traumatic brain injury (53% of patients) and cerebrovascular accidents (CVA) (23.3%). The rest of the patients had posthypoxic encephalopathy or were after brain tumor removal surgery. Passive orthostatic test (POT) 0° to 60° to 0° was performed using an electrically driven tilt table (Vario Line). Hemodynamic monitoring during the verticalization was done using a non-invasive oscillometric recording of blood pressure on the brachial artery, stroke volume (SV) and cardiac minute output (CMO) were measured by impedance cardiography with the multifunctional «Task Force Monitor 3010i» (CNSystem, Austria). Data were statistically analyzed using the Statistica 10 software package.Results. Orthostatic hemodynamic stability was found in 26 out of 30 patients with chronic disorders of consciousness after critical brain damage. It was manifested by stable systolic blood pressure (SBP) in tilted orthostatic and horizontal position (120.7±2.2 and 121.1±3.6 mmHg, respectively, P>0.05). Orthostatic hypotension was observed in 3 patients and postural tachycardia syndrome (PTS) in one patient. We compared orthostatic hemodynamic changes in the studied cohort versus published data on orthostatic hemodynamic changes uncluding POT revealed in patients with severe brain damage examined before and after brain death.Conclusion. Orthostatic stability of blood circulation can be maintained for a short period of time in patients surviving after critical diffuse brain damage associated with chronic disorders of consciousness. Critical brain damage resulting in brain death associates with a significant reduction of all hemodynamic parameters and severe orthostatic hypotension with restoration of initial blood pressure values when the patient is returned to the horizontal position.

Classical and Delayed Orthostatic Hypotension in Patients With Unexplained Syncope and Severe Orthostatic Intolerance.

Background: Orthostatic hypotension (OH) is a major sign of cardiovascular autonomic failure leading to orthostatic intolerance and syncope. Orthostatic hypotension is traditionally divided into classical OH (cOH) and delayed OH (dOH), but the differences between the two variants are not well-studied. We performed a systematic clinical and neuroendocrine characterization of OH patients in a tertiary syncope unit.Methods: Among 2,167 consecutive patients (1,316 women, 60.7%; age, 52.6 ± 21.0 years) evaluated for unexplained syncope and severe orthostatic intolerance with standardized cardiovascular autonomic tests including head-up tilt (HUT), we identified those with a definitive diagnosis of cOH and dOH. We analyzed patients' history, clinical characteristics, hemodynamic variables, and plasma levels of epinephrine, norepinephrine, C-terminal-pro-arginine-vasopressin (CT-proAVP), C-terminal-endothelin-1, mid-regional-fragment of pro-atrial-natriuretic-peptide and pro-adrenomedullin in the supine position and at 3-min HUT.Results: We identified 248 cOH and 336 dOH patients (27% of the entire cohort); 111 cOH and 152 dOH had blood samples collected in the supine position and at 3-min HUT. Compared with dOH, cOH patients were older (68 vs. 60 years, p < 0.001), more often male (56.9 vs. 39.6%, p < 0.001), had higher systolic blood pressure (141 vs. 137 mmHg, p = 0.05), had lower estimated glomerular filtration rate (73 vs. 80 ml/min/1.73 m2, p = 0.003), more often pathologic Valsalva maneuver (86 vs. 49 patients, p < 0.001), pacemaker-treated arrhythmia (5 vs. 2%, p = 0.04), Parkinson's disease (5 vs. 1%, p = 0.008) and reported less palpitations before syncope (16 vs. 29%, p = 0.001). Supine and standing levels of CT-proAVP were higher in cOH (p = 0.022 and p < 0.001, respectively), whereas standing norepinephrine was higher in dOH (p = 0.001). After 3-min HUT, increases in epinephrine (p < 0.001) and CT-proAVP (p = 0.001) were greater in cOH, whereas norepinephrine increased more in dOH (p = 0.045).Conclusions: One-quarter of patients with unexplained syncope and severe orthostatic intolerance present orthostatic hypotension. Classical OH patients are older, more often have supine hypertension, pathologic Valsalva maneuver, Parkinson's disease, pacemaker-treated arrhythmia, and lower glomerular filtration rate. Classical OH is associated with increased vasopressin and epinephrine during HUT, but blunted increase in norepinephrine.

OP201: A Phase 1/2 Study of Melflufen and Dexamethasone in Patients with Immunoglobulin Light Chain (AL) Amyloidosis

OP201: A Phase 1/2 Study of Melflufen and Dexamethasone in Patients with Immunoglobulin Light Chain (AL) Amyloidosis

Preanesthetic severe postural hypotension following 5-aminolevulinic acid pretreatment in patients for photodynamic diagnosis-assisted urological surgery

Background5-Aminolevulinic acid (5-ALA) is utilized for photodynamic diagnosis-assisted (PDD) surgery. However, it has been associated with vasodilation, hence, occasional hypotension.Case presentationWe encountered two patients who had severe postural hypotension following 5-ALA pretreatment prior to an operation. They were scheduled for urological PDD surgery, but upon standing to walk to the operation room, they felt sick because of severe hypotension. One of them underwent the surgery after recovery, but the other surgery was canceled due to a prolonged hypotension that lasted for more than a day.ConclusionsSevere postural hypotension may develop as a result of the high concentration of porphyrin precursors, which may affect the nervous system. Severe postural hypotension may be due to 5-ALA-induced autonomic dysfunction as well as vasodilative action of 5-ALA. These observations suggest that in addition to the careful monitoring of patients’ vital signs, standing should be avoided following 5-ALA pretreatment.

Seronegative autoimmune autonomic ganglionopathy from dual immune checkpoint inhibition in a patient with metastatic melanoma

BackgroundImmune checkpoint inhibitors have improved clinical outcomes including survival in several malignancies but have also been associated with a range of immune-related adverse events (irAEs). Neurological irAEs are rare compared to the more typical skin, gastrointestinal, and endocrine toxicities, and are often underrecognized and challenging to diagnose. Here, we report a case of seronegative autoimmune autonomic ganglionopathy (AAG) induced by dual immune checkpoint inhibitor therapy (ICI) in a patient with metastatic melanoma.Case presentationA patient with metastatic melanoma was treated with ipilimumab and nivolumab. He developed a constellation of new symptoms including nausea, fatigue, and severe orthostatic hypotension refractory to fluid resuscitation. An infectious, cardiac, neurologic, and endocrine workup were unrevealing. Cardiovascular autonomic testing revealed poor sympathetic nervous system responses. He was diagnosed with seronegative AAG and significantly improved with immunomodulatory therapies including IVIG and steroids as well as varying doses of midodrine and fludrocortisone. He was able to restart nivolumab without recurrence of his symptoms. However, the AAG reoccurred when he was re-challenged with ipilimumab and nivolumab due to disease progression. While the AAG was manageable with steroids at that time, unfortunately his melanoma became resistant to ICI.ConclusionsImmune checkpoint inhibitors can have a wide range of unusual, rare irAEs, including neurotoxicity such as AAG. Clinicians should maintain suspicion for this toxicity so that treatment can be rapidly provided to avoid disability.

Abstract P176: Familial Autonomic Ganglionopathy Caused by Rare CHRNA3 Genetic Variants. Novel Genetic Cause of Neurogenic Orthostatic Hypotension

Patients with autonomic failure developed severe neurogenic orthostatic hypotension (nOH). There are only two reported genetic conditions that cause nOH, dopamine β-hydroxylase deficiency, and CYB561 deficiency; both affect norepinephrine synthesis resulting in an isolated sympathetic failure. Objective: To determine molecular basis of a new Mendelian cause of familial nOH with impaired cardiovagal function, and miosis associated with sympathetic (SNS) and parasympathetic (PNS) failure. Method and Results: The proband developed disabling nOH with poor compensatory increase in heart rate at 39 yrs of age. Plasma norepinephrine levels were abnormally low. His sister had onset of nOH in her late teens. Their parents and brother were healthy. Whole exome sequencing of DNAs from the proband and his affected sister showed that both were compound heterozygotes for c.907_908delCT (p.L303Dfs*115) /c.688G&gt;A (p.D230N) variants in the acetylcholine receptor, neuronal nicotinic, alpha 3 subunit (CHRNA3) gene. CHRNA3 is a subunit of nicotinic acetylcholine receptors (nAChRs) that regulates blood pressure through modulation of synaptic transmission in the autonomic ganglia. The autonomic ganglia regulates both SNS and PNS activity. The frameshift (fs) and missense CHRNA3 variants were inherited from the sibs’ mother and father, respectively, and their non-affected brother was a nl/p.D230N heterozygote. The fs variant is obviously pathogenic and the p.D230N variant is predicted to be damaging (SIFT)/probably damaging (PolyPhen2). Furthermore, we predict from structural modeling that the p.D230N variant lies on the interface between CHRNA3 and other nAChR subunits and that it would destabilize the nAChR pentameric complex. In humans, the presence of acquired nAChR autoantibodies against the alpha 3 subunit is associated with nOH and non-reactive pupils. Conclusions: We report sibs affected with NOH and miosis who are compound heterozygotes forCHRNA3 variants that co-segregate with and have predicted effects on nAChR structure that suggest they likely cause this family’s SNS and PNS failure.

What do we really know about supine hypertension in patients with orthostatic hypotension.

Patients with severe orthostatic hypotension due to autonomic failure may be hypertensive in the supine position. Until recently, there were no internationally recognized diagnostic criteria for supine hypertension. This review covers diagnostic criteria, mechanisms, and management of supine hypertension in autonomic failure patients. Recently, an international consensus group defined supine hypertension in patients with neurogenic orthostatic hypotension as brachial SBP at least 140 mmHg and/or DBP at least 90 mmHg while supine. Using these criteria, a large proportion of patients with orthostatic hypotension is diagnosed with supine hypertension. Recent research supports the concept that the hypertension can be mediated through residual sympathetic nervous system function and independently from sympathetic activity, for example via mineralocorticoid receptor activation. The clear definition of supine hypertension is an important step that will hopefully foster clinical research in this area. Supine hypertension promotes renal sodium excretion, thus, worsening orthostatic hypotension the next morning. Supine hypertension may promote cardiovascular and renal disease. Yet, long-term benefits of treating supine hypertension be it through non pharmacological or pharmacological means have not been proven by sufficiently large clinical trials.

A case of Parkinson's disease following autoimmune autonomic ganglionopathy

AbstractThe patient is an 80‐year‐old man. At the age of 76, he presented with acute onset of severe orthostatic hypotension and diarrhea. Anti‐ganglionic acetylcholine receptor (anti‐gAChR) antibodies were positive, and prednisolone was effective. He was diagnosed with autoimmune autonomic ganglionopathy (AAG) based on acute onset autonomic dysfunction, positive anti‐gAChR antibodies, and efficacy of prednisolone. After the event of AAG, he gradually developed Parkinson's disease (PD). Parkinsonism is described as a complication of AAG in the previous literature. Anti‐gAChR antibodies might inhibit dopamine neurotransmission and be associated with the development of PD.

Clinical factors associated with the recovery of cardiovascular autonomic neuropathy in patients with type 2 diabetes mellitus

BackgroundCardiovascular autonomic neuropathy (CAN) is a major cause of morbidity and mortality in diabetes patients. Although several risk factors for CAN progression have been established, whether CAN is reversible remains unclear and the clinical factors associated with CAN recovery have not been identified. This study aimed to determine clinical factors related to CAN recovery.MethodsType 2 diabetes patients with CAN but free of cardiovascular disease at baseline were enrolled and followed for 2–3 years in this retrospective longitudinal study. CAN was classified as early (one abnormal parasympathetic test), definite (two or more abnormal parasympathetic tests), severe (definite plus orthostatic hypotension), or atypical (early plus orthostatic hypotension or orthostatic hypotension alone) based on Ewing’s method. CAN recovery was classified as partial or complete: Partial recovery was defined as one-step improvement in CAN stage (early to normal, definite to early, or severe to definite), including the disappearance of only one abnormal result in any stage. Complete recovery was defined as normalization from definite or severe CAN.ResultsAmong 759 subjects with CAN, 29.9% (n = 227) experienced CAN recovery, and 1.2% (n = 9) recovered completely. In a multivariate model, younger age (odds ratio [OR] per 5-year decrease 1.49; 95% confidence interval [CI] 1.25–1.78, P < 0.001), shorter duration of diabetes (OR per 5-year decrease 1.33; 95% CI 1.05–1.67, P = 0.016), presence of micro/macroalbuminuria (OR 0.34; 95% CI 0.15–0.78, P = 0.011), body weight reduction (OR per 1-kg decrease 1.11; 95% CI 1.02–1.21, P = 0.016), and HbA1c reduction (OR per 1% decrease 1.32; 95% CI 1.05–1.67, P = 0.019) were significantly associated with composite events of partial and complete CAN recovery. Age had the highest relative significance among the associated clinical factors. In addition, younger age was the only significant factor in complete CAN recovery.ConclusionsYounger age was the most important factor in CAN recovery in subjects with type 2 diabetes, including recovery from the definite or severe stage. HbA1c reduction, body weight reduction, no concurrent micro/macroalbuminuria, and shorter duration of diabetes were also significantly associated with CAN recovery.

Acute Autonomic Symptoms with Anti-myelin-associated Glycoprotein Neuropathy as a Presentation of Small B Cell Lymphoma: A Case Report and Literature Review

The association of symmetrical distal sensorimotor polyneuropathy with anti-myelin-associated glycoprotein antibodies (MAG) has been well established. Although autonomic symptoms are uncommon with anti-MAG antibody neuropathy (MAN). We are presenting an unusual case, who developed acute onset urinary retention, orthostatic hypotension, bradycardia and was found to have MAN. She was a 68-year-old lady, presented with progressive ascending numbness, weakness of her extremities and balance problems. On neurological examination, she had generalized muscle weakness, reduced perception to all modalities of sensation with marked impairment of vibration and position sense in the lower limbs. Reflexes were diminished throughout and Romberg sign was positive. Initial lab work including thyroid-stimulating hormone (TSH), vitamin B12, Hb1c, and routine lab reports was normal. The patient then developed acute urinary retention, severe orthostatic hypotension, and symptomatic bradycardia. Workup during this time revealed M spike on serum electrophoresis with IgM kappa on immunofixation. IgM titers were higher than normal. Initially, she was thought to have monoclonal gammopathy of undetermined significance (MGUS) related neuropathy but further workup showed very high levels of anti-MAG antibody titer. Further workup including a bone marrow biopsy revealed a small B cell lymphoma. Only a few cases have reported a small B cell lymphoma presenting with MAN-associated autonomic symptoms. She is currently being treated with rituximab with significant improvement in her neuropathic symptoms. Further case studies are needed to show whether autonomic symptoms are the feature of MAN or this atypical presentation is the paraneoplastic manifestation of the lymphoma.

A Case Report of Pediatric Paraneoplastic Dysautonomia

We present the case of a 16-year-old girl who presented with severe refractory orthostatic hypotension secondary to pandysautonomia. Initially, she was treated for Guillain-Barré syndrome given clinical symptoms and increased protein on cerebrospinal fluid, but the severity of symptoms and lack of response to intravenous immunoglobulin prompted further evaluation for an autoimmune etiology. She was ultimately diagnosed with paraneoplastic neuropathy secondary to Hodgkin lymphoma. Paraneoplastic neurologic phenomena are rare, occurring in just 0.01% of cancers, and prompt recognition is crucial for initiating appropriate therapy. Rapid progression of severe disabling symptoms should raise suspicion for an underlying malignancy. The patient had limited response to splanchnic vasoconstrictors in addition to α-agonists, anticholinergics, and mineralocorticoids until initiation of modified Hodgkin lymphoma directed chemotherapy plus rituximab.

Improvement in Severe Orthostatic Hypotension Following Carbidopa Dose Reduction

Improvement in Severe Orthostatic Hypotension Following Carbidopa Dose Reduction

Severe Orthostatic Hypotension Complicating Multiple Myeloma

Introduction Amyloidosis is a well-recognized complication of multiple myeloma, although isolated vascular amyloidosis of the kidney is relatively rare. Vascular amyloidosis is associated with fewer urinary findings than the more common glomerular amyloidosis, and may present both diagnostic and treatment challenges, particularly when performing renal replacement therapy. Case description We present a 53-year-old man who presented with light-headedness complicated by multiple falls, severe orthostatic hypotension, and acute kidney injury. The patient was ultimately diagnosed with multiple myeloma. His course was complicated by progressively worsening kidney function, which necessitated renal replacement therapy, and persistent symptoms of orthostatic hypotension despite maximal medical therapy. A kidney biopsy revealed light chain cast nephropathy and isolated vascular amyloidosis of the kidney. Hemodialysis and subsequently continuous veno-venous hemodialysis were poorly tolerated due to severe hemodynamic instability. Ultimately, the patient suffered a fatal cardiac arrest. Conclusions This case provides a platform to discuss clinical aspects and diagnosis of vascular-limited renal amyloidosis. In addition, we address the difficulty in managing a patient with severe hemodynamic instability due to this disease.

Severe orthostatic hypotension after adding low-dose aripiprazole to clozapine

Address for correspondence: Chih-Sung Liang. Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC; Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, ROC. No.60, Xinmin Road, Beitou District, Taipei City 112, Taiwan, ROC. Tel: +886-2-2895-9808; Fax: +886-2-2895-7633. E-mail: lcsyfw@gmail.com

The dawn of cardiovascular neuroprosthetics: Epidural spinal cord stimulation acutely restores cardiovascular function in persons with clinically complete spinal cord injury

INTRODUCTIONNeuroprosthetic electrical stimulation of the lumbosacral spinal cord with surgical implants has the capacity to excite dormant neuronal circuitry that has lost supraspinal control due to a spinal cord injury. Very recently, this intervention was even shown to elicit involuntary and voluntary stepping‐like movement of skeletal muscles previously thought to be paralyzed.OBJECTIVEConsidering that autonomic and cardiovascular dysfunctions are the leading cause of death after spinal cord injury, and a higher health priority than walking again by these individuals, we set out to explore if lumbosacral electrical stimulation of the spinal cord could be harnessed to regulate the cardiovascular system after spinal cord injury.METHODSThree of the first individuals with cervical spinal cord injury to be implanted worldwide were assessed in the present study, all of whom presented with cardiovascular dysfunction, in the form of severe orthostatic hypotension as well as impaired cardiac and cerebral regulation. A 16‐electrode array (Fig A) paddle was implanted over the lower lumbar/sacral spinal cord segments and connected to an electrical stimulation unit (both Medtronic). At least one month after implantation, we developed a cardiovascular optimized stimulation paradigm, that excited sympathetic preganglionic neurons but did not elicit skeletal muscle contraction (confirmed with electromyography; Fig A). We measured beat‐by‐beat blood pressure (photoplethysmography), cardiac function (echocardiography), and cerebral blood flow regulation (transcranial Doppler), in the supine position and in response to sit‐up, as well as cognitive function (Stroop test) with and without (in randomized order) cardiovascular optimized stimulation. Statistics on only one to three individuals is not typically recommended and was not performed.RESULTSTargeted cardiovascular electrical stimulation resulted in: [1] abrogated orthostatic hypotension (–39mmHg and severe presyncope vs. −8mmHg and absence of symptoms; Fig A,B); [2] maintained stroke volume (−32ml vs. −8ml; Fig 1E) and cerebral blood flow (−25 cm/s vs. −6cm/s; Fig B) during sit‐up; and [3] restored neurovascular coupling Fig C (+0% vs. 18%); and Stroop performance (P3–P2 time: 42s vs. 21s). Increased low‐frequency power of systolic blood pressure oscillations suggest supraspinal medullary sympathetic control of blood pressure is restored Fig D.CONCLUSIONSNeuroprosthetic modulation of spinal cord circuitry caudal to injury can restore normal autonomic control, which challenges our dogmatic understanding of the inherent functionality of the autonomic pathways in the spinal cord after injury. This data may represent the dawn of a new age for neuroprosthetic management of autonomic and cardiovascular heath.Support or Funding InformationCraig Neilsen Foundation, Rick Hansen Institute, Helmsley Foundation Research Trust.

Servelle-martorell syndrome with severe orthostatic hypotension in a pediatric patient

Servelle-Martorell syndrome (SMS) is an extremely uncommon vascular malformation characterized by venous malformations (VMs), limb overgrowth, and bone hypotrophy. The most common complications are venous thrombosis and pathological fractures. Ectasia and aneurysmal dilatations of the superficial veins may result in overgrowth of soft tissues but shortening of the affected limb. We report an 11-year-old Hispanic boy with an enlarged lower limb and VM. The patient suffered a fall at 9 years of age resulting in ankylosis of the knee without the possibility of limb extension or walking. When he tried to stand up, a severe orthostatic hypotension and almost loss of consciousness were present. An angio computed tomography and an arteriography demonstrated a complete absence of the deep venous system and bony hypotrophy compatible with SMS.