Familial dysautonomia.

Familial dysautonomia (FD) is an autosomal recessive hereditary sensory and autonomic neuropathy (HSAN, type 3) expressed at birth with profound sensory loss and early death. The FD founder mutation in the ELP1 gene arose within the Ashkenazi Jews in the sixteenth century and is present in 1:30 Jews of European ancestry. The mutation yield a tissue-specific skipping of exon 20 and a loss of function of the elongator-1 protein (ELP1), which is essential for the development and survival of neurons. Patients with FD produce variable amounts of ELP1 in different tissues, with the brain producing mostly mutant transcripts. Patients have excessive blood pressure variability due to the failure of the IXth and Xth cranial nerves to carry baroreceptor signals. Neurogenic dysphagia causes frequent aspiration leading to chronic pulmonary disease. Characteristic hyperadrenergic "autonomic crises" consisting of brisk episodes of severe hypertension, tachycardia, skin blotching, retching, and vomiting occur in all patients. Progressive features of the disease include retinal nerve fiber loss and blindness, and proprioceptive ataxia with severe gait impairment. Chemoreflex failure may explain the high frequency of sudden death in sleep. Although 99.5% of patients are homozygous for the founder mutation, phenotypic severity varies, suggesting that modifier genes impact expression. Medical management is currently symptomatic and preventive. Disease-modifying therapies are close to clinical testing. Endpoints to measure efficacy have been developed, and the ELP1 levels are a good surrogate endpoint for target engagement. Early intervention may be critical for treatment to be successful.

Lateralizing sensorimotor deficits in a case of pseudopheochromocytoma.

Pseudopheochromocytoma is a poorly understood, rare cause of severe paroxysmal hypertension that mimics the symptomatology of pheochromocytoma in the absence of biochemical evidence of this tumor. Symptoms such as headache, nausea, sweating, and palpitations during hypertensive episodes have been described. In this paper, we describe previously unreported findings of lateralizing sensorimotor deficits in a patient with pseudopheochromocytoma. These changes presented during a hypertensive episode and were concerning for stroke but were not accompanied by acute radiologic abnormalities. The deficits improved over 1.5 weeks as blood pressure stabilized with beta-blockade. We also review relevant literature on the clinical features, pathophysiology, and management of pseudopheochromocytoma.

The unpredictability of labile blood pressure: Afferent baroreflex failure in a critical patient with multiple thyroid surgeries and COVID-19 infection.

The carotid sinus-arterial baroreflex is essential in maintaining blood pressure (BP) regulation. Afferent baroreflex failure (ABF) can present with labile changes in BP within seconds and can be secondary to neck surgery or radiation. We present here the first case, to our knowledge, of ABF precipitated by thyroidectomy, in a patient with active COVID-19 pneumonia, causing difficult control of severely labile BP in a critical care unit. Contributing factors included her critical illness state with upregulation of IL-6 leading to pituitary-adrenal axis alteration, her thyroidectomy further exacerbating autonomic dysfunction, as well as downregulation of ACE2 via COVID-19 infection. Management was achieved with a combination of midodrine and clonidine catered to specific BP thresholds. Additional research with a multidisciplinary approach is warranted to fully optimize the treatment of ABF in patients with neck surgery and or inflammatory conditions such as COVID-19.