Objective
In this narrative review, we summarize experimental and clinical evidence demonstrating mechanistic connections between POTS and migraine.
Background
Migraine is the most common comorbidity ...in patients with POTS, a heterogenous disorder of the autonomic nervous system characterized by orthostatic intolerance and positional tachycardia. POTS is a debilitating illness with few effective treatments. We aim for this narrative review to increase awareness of the mechanistic connections between POTS and migraine providing foundational information that optimizes clinical care and advances the development of pathophysiologic‐based treatments.
Methods
We used the PubMed and Medline databases in November 2021 to perform a literature review and searched for the following keywords: “postural orthostatic tachycardia syndrome,” “POTS,” “autonomic nervous system,” AND “migraine,” “headache.”
Results
The high prevalence of migraine in patients with POTS may be explained by common pathologic mechanisms. There is evidence that dysregulation of the sympathetic nervous system, alterations in central and peripheral hemodynamics, and central sensitization increase vulnerability to both POTS and migraine. Non‐pharmacologic and pharmacologic treatments that target these shared mechanisms may provide significant benefit for the patient with POTS and migraine.
Conclusions
Identification of common affected pathways may provide important insight that advances our understanding and treatment of both migraine and POTS.
Objective
To identify the characteristics associated with high utilization of remote communications (RCs) in patients with headache.
Background
Patients with headache frequently communicate with ...their providers using secure portal messaging and telephone calls. However, clinical and demographic factors as well as visit patterns associated with RC utilization remain poorly characterized.
Methods
We retrospectively analyzed data from patients with headache who were evaluated in the ambulatory neurology faculty practice at the Icahn School of Medicine at Mount Sinai in New York between January 1 and June 30, 2019. We extracted clinical and demographic characteristics, total office visits, secure MyChart portal messages, and telephone encounters from our institutional data warehouse. We defined high RC and MyChart utilization as the top tertile of RC and MyChart message volume, respectively, and assessed the relationship between patient characteristics and high RC (primary outcome), as well as high MyChart utilization (secondary outcome). We characterized the relationship between clinicodemographic characteristics and the ratio of MyChart messages to total RCs (secondary outcome).
Results
We identified 1390 patients, of whom 477 (34.3%) were high RC utilizers and 321 (23.1%) were high MyChart utilizers. High RC utilizers generated 3306/3921 (84.3%) RCs. The presence of chronic headache (aOR 2.31, 95% CI 1.75–3.03, p < 0.0001), cluster headache (aOR 18.3, 95% CI 5.0–71.7, p = 0.001), and migraine (aOR 3.82, 95% CI 1.93–9.3, p = 0.011) was associated with high RC utilization. Patients ≥65 years of age were less likely to engage in MyChart messaging as a proportion of RC (191/680, 28.1%) compared with patients 18–30 years of age (243/620, 39.2%, p = 0.049) and 30–64 years of age (1172/2721, 43.1%, p < 0.0001).
Conclusions
A minority of patients with headache (477/1390; 34.3%) generated the majority (3306/3921; 84.3%) of RCs. Our findings should be validated in external patient cohorts with the objective of developing strategies to optimize RC utilization.
ABSTRACT
BACKGROUND AND PURPOSE
Human immunodeficiency virus (HIV)‐infected patients commonly have abnormalities in cerebral white matter that are visible on magnetic resonance imaging (MRI) as ...hyperintensities (WMHs). Visual rating scales (VRSs) have been used to quantify WMH in other diseases such as cerebral small vessel disease (CSVD), but not in HIV. Such scales are advantageous because they are applicable to routinely acquired MRIs and so are suitable for large‐scale studies and clinical care. We sought to establish the utility of three VRSs (the Fazekas, Scheltens, and van Sweiten scales) in HIV.
METHODS
The Manhattan HIV Brain Bank (MHBB) is a longitudinal cohort study that performs serial neurologic examinations and neuropsychological testing. All brain MRIs (n = 73) performed for clinical purposes on MHBB participants were scored using the three VRSs. We assessed reliability, validity, and correlation of the VRS with clinical factors relevant to HIV and CSVD.
RESULTS
The VRSs all showed acceptable internal consistency and interrater reliability and were highly correlated with one another (r = 0.836‐0.916, P < .001). The Fazekas and Scheltens scales demonstrated more WMH in periventricular regions, and the Scheltens scale also suggested a frontal to occipital gradient, with greater WMH frontally. All three VRSs correlated significantly with cognitive impairment (global T score). Age and hepatitis C virus antibody serostatus were the strongest clinical/demographic correlates of WMH, followed by African‐American race.
CONCLUSIONS
VRSs reliably quantify WMH in HIV‐infected individuals and correlate with cognitive impairment. Future studies may find routinely acquired brain MRI quantified by VRS to be an accessible and meaningful neurologic outcome measure in HIV.
The autonomic nervous system (ANS), hypothalamic–pituitary–adrenal (HPA) axis, and immune system are connected anatomically and functionally. These three systems coordinate the central and peripheral ...response to perceived and systemic stress signals. Both the parasympathetic and sympathetic components of the autonomic nervous system rapidly respond to stress signals, while the hypothalamic–pituitary–adrenal axis and immune system have delayed but prolonged actions. In vitro, animal, and human studies have demonstrated consistent anti-inflammatory effects of parasympathetic activity. In contrast, sympathetic activity exerts context-dependent effects on immune signaling and has been associated with both increased and decreased inflammation. The location of sympathetic action, adrenergic receptor subtype, and timing of activity in relation to disease progression all influence the ultimate impact on immune signaling. This article reviews the brain circuitry, peripheral connections, and chemical messengers that enable communication between the ANS, HPA axis, and immune system. We describe findings of in vitro and animal studies that challenge the immune system with lipopolysaccharide. Next, neuroimmune connections in animal models of chronic inflammatory disease are reviewed. Finally, we discuss how a greater understanding of the ANS-HPA-immune network may lead to the development of novel therapeutic strategies that are focused on modulation of the sympathetic and parasympathetic nervous system.
Objectives
Early presentation and workup for acute infectious (IE) and autoimmune encephalitis (AE) are similar. This study aims to identify routine laboratory markers at presentation that are ...associated with IE or AE.
Methods
This was a multi‐center retrospective study at three tertiary care hospitals in New York City analyzing demographic and clinical data from patients diagnosed with definitive encephalitis based on a confirmed pathogen and/or autoantibody and established criteria for clinical syndromes.
Results
Three hundred and thirty‐three individuals with confirmed acute meningoencephalitis were included. An infectious‐nonbacterial (NB) pathogen was identified in 151/333 (45.40%), bacterial pathogen in 95/333 (28.50%), and autoantibody in 87/333 (26.10%). NB encephalitis was differentiated from AE by the presence of fever (NB 62.25%, AE 24.10%; p < 0.001), higher CSF white blood cell (WBC) (median 78 cells/μL, 8.00 cells/μL; p < 0.001), higher CSF protein (76.50 mg/dL, 40.90 mg/dL; p < 0.001), lower CSF glucose (58.00 mg/dL, 69.00 mg/dL; p < 0.001), lower serum WBC (7.80 cells/μL, 9.72 cells/μL; p < 0.050), higher erythrocyte sedimentation rate (19.50 mm/HR, 13.00 mm/HR; p < 0.05), higher C‐reactive protein (6.40 mg/L, 1.25 mg/L; p = 0.005), and lack of antinuclear antibody titers (>1:40; NB 11.54%, AE 32.73%; p < 0.001). CSF‐to‐serum WBC ratio was significantly higher in NB compared to AE (NB 11.3, AE 0.99; p < 0.001). From these findings, the association of presenting with fever, CSF WBC ≥50 cells/μL, and CSF protein ≥75 mg/dL was explored in ruling‐out AE. When all three criteria are present, an AE was found to be highly unlikely (sensitivity 92%, specificity 75%, negative predictive value 95%, and positive predictive value 64%).
Interpretations
Specific paraclinical data at initial presentation may risk stratify which patients have an IE versus AE.
Objective
Preliminary evidence suggests that chronic pain patients complete pain intensity measures using idiosyncratic methods. Our objective was to understand these methods and how they might ...impact the psychometric properties of the instruments.
Design
A qualitative focus‐group based study.
Setting
An academic center in New York City.
Subjects
Outpatients (n = 36) with chronic low back pain, or neuropathic pain due to diabetes or HIV.
Methods
Participants were divided into three focus groups based on their pain condition, and asked to discuss pain intensity measures (visual analog and numeric rating scales for average pain over 24 hours; Brief Pain Inventory; and McGill Pain Questionnaire). Audio‐recordings were transcribed and analyzed using an inductive thematic method.
Results
We discovered four main themes, and five sub‐themes: 1) doubt that pain can be accurately measured (subthemes: pain measurement is influenced by things other than pain, the numbers used to rate pain do not have an absolute meaning, and preference for pain intensity ratings “in the middle” of the scale); 2) confusion regarding the definition of pain; 3) what experiences to use as referents (subthemes: appropriate comparator experiences and the interpretation of the anchors of the scale); and 4) difficulty averaging pain.
Conclusions
The themes discovered suggest that patients include sensations and experiences other than pain intensity in their ratings, experience the rating of pain as a comparative task, and do not use the scale in a linear manner. These themes are relevant to understanding the validity and scale properties of commonly used pain intensity measures.
Non-cephalgic symptoms including orthostatic intolerance, fatigue, and cognitive impairment, are common in patients with chronic headache disorders and may result from alterations in the autonomic ...nervous system. However, little is known about the function of autonomic reflexes, which regulate cardiovascular homeostasis and cerebral perfusion in patients with headache.
Autonomic function testing data from patients with headache collected between January 2018 and April 2022 was retrospectively analyzed. Through review of EMR we determined headache pain chronicity and patient self-report of orthostatic intolerance, fatigue, and cognitive impairment. Composite Autonomic Severity Score (CASS), CASS subscale scores, and cardiovagal and adrenergic baroreflex sensitivities were used to quantify autonomic reflex dysfunction. Descriptive analyses (Mann-Whitney-
or χ
, as appropriate) determined associations between autonomic reflex dysfunction and POTS as well as chronic headache. Binomial logistic regression adjusted for age and sex. Spearman's rank correlation determined the association between the total CASS score and the number of painless symptoms reported by each participant.
We identified 34 patients meeting inclusion criteria, of whom there were 16 (47.0%) with orthostatic intolerance, 17 (50.0%) with fatigue, 11 (32.4%) with cognitive complaints, and 11 (32.4%) with Postural Orthostatic Tachycardia Syndrome (POTS). The majority of participants had migraine (
= 24, 70.6%), were female (
= 23, 67.6%) and had a chronic (>15 headache days in a month) headache disorder (
= 26, 76.5%). Reduced cardiovagal baroreflex sensitivity (BRS-V) independently predicted chronic headache aOR: 18.59 (1.16, 297.05),
= 0.039 and POTS aOR: 5.78 (1.0, 32.5),
= 0.047. The total CASS was correlated with the total number of non-painful features in the expected direction (
= 0.46,
= 0.007).
Abnormal autonomic reflexes may play an important role in pain chronification and the development of POTS in patients with headache.
Neuromuscular disorders are common in human immunodeficiency virus (HIV); they occur at all stages of disease and affect all parts of the peripheral nervous system. These disorders have diverse ...etiologies including HIV itself, immune suppression and dysregulation, comorbid illnesses and infections, and side effects of medications. In this article, we review the following HIV‐associated conditions: distal symmetric polyneuropathy; inflammatory demyelinating polyneuropathy; mononeuropathy; mononeuropathy multiplex; autonomic neuropathy; progressive polyradiculopathy due to cytomegalovirus; herpes zoster; myopathy; and other, rarer disorders. Muscle Nerve, 2009
The mechanism producing psychosis appears to include hippocampal inflammation, which could be associated with the microbiome-gut-brain-axis (MGBS). To test this hypothesis we are conducting a ...multidisciplinary study, herein described. The procedures are illustrated with testing of a single subject and group level information on the impact of C-section birth are presented.
Study subjects undergo research diagnostic interviews and symptom assessments to be categorized into one of 3 study groups: psychosis, nonpsychotic affective disorder or healthy control. Hippocampal volume and metabolite concentrations are assessed using 3-dimensional, multi-voxel H1 Magnetic Resonance Imaging (MRSI) encompassing all gray matter in the entire hippocampal volume. Rich self-report information is obtained with the PROMIS interview, which was developed by the NIH Commons for research in chronic conditions. Early trauma is assessed and cognition is quantitated using the MATRICS. The method also includes the most comprehensive autonomic nervous system (ANS) battery used to date in psychiatric research. Stool and oral samples are obtained for microbiome assessments and cytokines and other substances are measured in blood samples.
Group level preliminary data shows that C-section birth is associated with higher concentrations of GLX, a glutamate related hippocampal neurotransmitter in psychotic cases, worse symptoms in affective disorder cases and smaller hippocampal volume in controls.
Mode of birth appears to have persistent influences through adulthood. The methodology described for this study will define pathways through which the MGBA may influence the risk for psychiatric disorders.
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