Interventions associated with brown adipose tissue activation and the impact on energy expenditure and weight loss: A systematic review

BackgroundBrown adipose tissue (BAT) plays a role in modulating energy expenditure. People with obesity have been shown to have reduced activation of BAT. Agents such as β-agonists, capsinoids, thyroid hormone, sildenafil, caffeine, or cold exposure may lead to activation of BAT in humans, potentially modulating metabolism to promote weight loss.MethodsWe systematically searched electronic databases for clinical trials testing the effect of these agents and cold exposure on energy expenditure/thermogenesis and the extent to which they may impact weight loss in adults.ResultsA total of 695 studies from PubMed, Web of Science, and Medline electronic databases were identified. After the removal of duplicates and further evaluation, 47 clinical trials were analyzed. We observed significant heterogeneity in the duration of interventions and the metrics utilized to estimate thermogenesis/energy expenditure. Changes observed in energy expenditure do not correlate with major weight changes with different interventions commonly known to stimulate thermogenesis. Even though cold exposure appears to consistently activate BAT and induce thermogenesis, studies are small, and it appears to be an unlikely sustainable therapy to combat obesity. Most studies were small and potential risks associated with known side effects of some agents such as β-agonists (tachycardia), sibutramine (hypertension, tachycardia), thyroid hormone (arrhythmias) cannot be fully evaluated from these small trials.ConclusionThough the impact of BAT activation and associated increases in energy expenditure on clinically meaningful weight loss is a topic of great interest, further data is needed to determine long-term feasibility and efficacy

Abstract Number ‐ 226: Pontine Stroke Presenting as 1.5 Syndrome Evolving to 9 Syndrome over 72 Hours.

Introduction A 75 year old woman with a past medical history of hypertension developed sudden‐onset vertigo, nausea and vomiting. She did not immediately seek medical care, thinking she was suffering from food poisoning. The following day her symptoms improved however she developed new right sided weakness and gait imbalance, prompting her presentation to the ED. Her neurologic exam noted complete loss of adduction of the right eye and loss of horizontal extraocular movements of the left eye. She also displayed right upper extremity paresis, right upper extremity dysmetria and mild dysarthria. MRI of the brain disclosed acute pontine infarcts in the ventral and dorsal left paramedian regions. Over the next three days, her horizontal gaze palsy improved with some return of adduction of the right eye and horizontal movements of the left eye. However right sided paresis worsened, and in addition, progressed to include complete left facial palsy (lower motor neuron lesion). She was able to be discharged to rehab, placed on Aspirin 81 mg daily and Ezetimibe (due to elevated liver function enzymes) and 30 day Cardiac Event Monitor follow up. Methods Case report and review of literature. Results Due to the combination of multiple cranial nuclei and white matter tracts in the brainstem, ischemia can lead to several clinical manifestations. There are various presenting clinical syndromes, named numerically by structures involved and/or the clinical deficit. One‐and‐a‐half (1.5) syndrome, first reported by Fischer in 1967, is an uncommon entity caused by a lesion (most commonly infarction) in the pontine tegmentum [1]. It consists of complete ipsilateral horizontal gaze palsy (due to involvement of ipsilateral Paramedian Pontine Reticular Formation/Abducens Nucleus and Medial Longitudinal Fasciculus) and loss of adduction of the contralateral eye (due to involvement of the contralateral Medial Longitudinal Fasciculus). Extension of the lesion to the facial nucleus can produce ipsilateral lower motor neuron type facial palsy, leading to an even more uncommon 8.5 syndrome (7 + 1.5), described by Eggenberger in 1998 [2]. When the lesion involves the corticospinal tracts and/or the medial lemniscus, it can lead to contralateral hemiparesis and/or hemisensory deficits; the so called “9 syndrome” first proposed by Rosini et al in 2013 [3]. This rare entity has been reported in only a handful of cases. Conclusions The awareness of complex brainstem neuroanatomy enables precise localization of the clinical deficits. The noted slow progression of the clinical syndrome from 1.5 to 8.5 and finally 9 syndrome over 72 hours in this case highlights the complexity of small vessel brainstem ischemia

Abstract Number ‐ 269: Brainstem Stroke Secondary to Lyme Neuroborreliosis Vasculitis

Introduction Clinical presentations of Lyme disease are variable. A rash is often the first symptom, subsequently evolving into late complications including arthritic, cardiac, and neurological manifestations. CNS pathologies of Borrelia burgdorferi are diverse and usually include meningitis, encephalitis, strokes, intracranial hemorrhages, and central and peripheral cranial neuropathies. Stroke secondary to Lyme vasculitis is a rare entity as such there are few cases reported in the literature. The presumed mechanism of cerebral ischemia is perivascular and vascular lymphocytic infiltration causing inflammation and vasculitis, resulting in a stroke. Methods We present a case of neuroborreliosis from our stroke service in a patient who presented with sudden onset of right‐sided facial droop, dizziness, and difficulty walking. Results A 53‐year‐old male tobacco smoker (his only known risk factor for stroke) presented to the emergency department with acute onset right‐sided facial paresis, difficulty walking, double vision, and trouble managing his oropharyngeal secretions. CT Head showed no acute intracranial pathology and angiography was negative for proximal large vessel occlusion. He was eligible for and received intravenous alteplase due to concerns for acute ischemic stroke. Notably, he disclosed a history of a tick bite (roughly two and half years prior) and daily headaches (for the past 1.5 months). His exam revealed bidirectional nystagmus, negative head impulse, right LMN facial nerve palsy, left‐sided face and arm numbness, and left‐sided tongue weakness. MRI brain revealed acute infract in the right medulla, leptomeningeal and bilateral cranial (3rd, 5th, and 7th) nerves enhancement. Serum Lyme IgG and IgM antibodies were positive. Lumbar puncture revealed an elevated protein with lymphocytic predominance. CSF Lyme antibody revealed 3 bands of IgG and 1 band of IgM, consistent with Lyme meningitis. Intravenous Ceftriaxone was started and his difficulty walking and cranial neuropathies improved during the hospital course. The patient required g‐tube placement and was discharged to sub‐acute rehab. A four‐month follow MRI brain showed decreased cranial nerve enhancement without new evidence of ischemia. He eventually regained the ability to swallow, and his exam had otherwise returned to baseline. Conclusions The proposed mechanism of ischemic stroke due to Lyme Neuroborreliosis is secondary to localized inflammatory vasculitis. Lyme vasculitis can present with hemorrhagic or ischemic strokes, the latter being more common and usually affecting posterior circulation, as seen in this case. Negative CTA or transcranial Doppler studies do not exclude the diagnosis of arteriopathy as stenosis primarily involves small vessels and is usually segmental. Parenchymal brain imaging often reveals multiple territory strokes, leptomeningeal, and multiple cranial nerves enhancement in contrast studies. A thorough history of tick exposure or symptoms consistent with Erythema Migrans should be obtained in suspicious cases. Notably, patients will often complain of meningitic symptoms (including headache, neck stiffness, and malaise) usually weeks to months before any stroke‐like symptoms or deficits. Our case of Lyme Neuroborreliosis presenting as stroke illustrates the importance of considering rare etiologies in younger patients without any significant cerebrovascular risk factors, especially those residing in or traveling to endemic areas

Table_1_Interventions associated with brown adipose tissue activation and the impact on energy expenditure and weight loss: A systematic review.docx

BackgroundBrown adipose tissue (BAT) plays a role in modulating energy expenditure. People with obesity have been shown to have reduced activation of BAT. Agents such as β-agonists, capsinoids, thyroid hormone, sildenafil, caffeine, or cold exposure may lead to activation of BAT in humans, potentially modulating metabolism to promote weight loss.MethodsWe systematically searched electronic databases for clinical trials testing the effect of these agents and cold exposure on energy expenditure/thermogenesis and the extent to which they may impact weight loss in adults.ResultsA total of 695 studies from PubMed, Web of Science, and Medline electronic databases were identified. After the removal of duplicates and further evaluation, 47 clinical trials were analyzed. We observed significant heterogeneity in the duration of interventions and the metrics utilized to estimate thermogenesis/energy expenditure. Changes observed in energy expenditure do not correlate with major weight changes with different interventions commonly known to stimulate thermogenesis. Even though cold exposure appears to consistently activate BAT and induce thermogenesis, studies are small, and it appears to be an unlikely sustainable therapy to combat obesity. Most studies were small and potential risks associated with known side effects of some agents such as β-agonists (tachycardia), sibutramine (hypertension, tachycardia), thyroid hormone (arrhythmias) cannot be fully evaluated from these small trials.ConclusionThough the impact of BAT activation and associated increases in energy expenditure on clinically meaningful weight loss is a topic of great interest, further data is needed to determine long-term feasibility and efficacy.</p