Faculty Bibliography

: Supine hypertension commonly occurs in patients with neurogenic orthostatic hypotension due to autonomic failure. Supine hypertension promotes nocturnal sodium excretion and orthostatic hypotension, thus, interfering with quality of life. Perusal of the literature on essential hypertension and smaller scale investigations in autonomic failure patients also suggest that supine hypertension may predispose to cardiovascular and renal disease. These reasons provide a rationale for treating supine hypertension. Yet, treatment of supine hypertension, be it through nonpharmacological or pharmacological approaches, may exacerbate orthostatic hypotension when patients get up during the night. Fall-related complications may occur. More research is needed to define the magnitude of the deleterious effects of supine hypertension on cardiovascular, cerebrovascular, and renal morbidity and mortality. Integration of more precise cardiovascular risk assessment, efficacy, and safety data, and the prognosis of the underlying condition causing autonomic failure is required for individualized management recommendations.

PURPOSE/OBJECTIVE:Familial dysautonomia (FD) is a rare autosomal recessive disease that affects the development of sensory and autonomic neurons, including those in the cranial nerves. We aimed to determine whether conventional brain magnetic resonance imaging (MRI) could detect morphologic changes in the trigeminal nerves of these patients. METHODS:Cross-sectional analysis of brain MRI of patients with genetically confirmed FD and age- and sex-matched controls. High-resolution 3D gradient-echo T1-weighted sequences were used to obtain measurements of the cisternal segment of the trigeminal nerves. Measurements were obtained using a two-reader consensus. RESULTS:in controls (P < 0.001). No association between trigeminal nerve area and age was found in patients or controls. CONCLUSIONS:Using conventional MRI, the caliber of the trigeminal nerves was significantly reduced bilaterally in patients with FD compared to controls, a finding that appears to be highly characteristic of this disorder. The lack of correlation between age and trigeminal nerve size supports arrested neuronal development rather than progressive atrophy.

Hypokalemia of renal origin can arise from genetic abnormalities in a variety of transporters or channel proteins that mediate tubular handling of potassium. Recently, mutations in claudin 10 have been documented in patients with hypokalemia in association with a range of other electrolyte abnormalities and skin and sweat gland manifestations. We report a 12-year-old Hispanic boy who presented with anhydrosis, aptyalism, alacrima, hypokalemia, and hypocalciuria, in whom we detected a homozygous mutation in the claudin 10 gene. During the 4-year follow-up period, he developed hypermagnesemia and a decline in estimated glomerular filtration rate to 59mL/min/1.73m². His unaffected parents and siblings were heterozygous for the mutation. We summarize the clinical phenotype encountered in patients with claudin 10 mutations. It is characterized by significant heterogeneity in electrolyte and extrarenal abnormalities and is associated with a risk for progressive loss of kidney function in up to 33% of cases. Awareness of this association between claudin 10 mutations and electrolyte abnormalities, namely hypokalemia and hypermagnesemia, sheds new light on the physiology of potassium and magnesium handling along the nephron and increases the likelihood of identifying the underlying tubular mechanism in patients with newly diagnosed hypokalemia with or without concomitant hypermagnesemia.

OBJECTIVES/OBJECTIVE:Familial dysautonomia (FD) is a rare hereditary sensory and autonomic neuropathy characterized by chronic lung disease and cyclic vomiting due to hyper-adrenergic crises. Most FD patients are in a depleted nutritional state; however the phenotype of the disease is quite different between patients, as for the severity of lung disease and the intensity and frequency of these pathognomonic crises. In this study we wanted to investigate whether resting energy expenditure (REE) levels are increased in this population, and if correlations exist between REE levels and phenotype severity. METHODS:Data was collected from 12 FD patients (6/6 m/f). REE measurements were conducted by indirect calorimeter. Measured REE % predicted were correlated with pulmonary function, severity of the scoliosis, serum C- reactive protein, yearly frequency of hyper-adrenergic crisis, hospital admissions and the use of nocturnal noninvasive positive pressure ventilation. RESULTS:Mean REE was 112 ±13% predicted with 50% being in a hypermetabolic state (REE/HB > 110%). Body Mass Index (BMI) was below normal range in 75% of patients, and reduced energy intake was also decreased in 75%. No significant correlations to disease severity factors were found. When dividing the subjects to REE levels above or below 125% predicted, Patients with REE above 125% predicted presented with significantly lower Inspiratory Capacity (IC) (42.7% predicted vs 62.8% predicted; p=0.04). CONCLUSIONS:Hypermetabolic state was described in 50% of FD patients. The Low BMI is explained by combination of relative anorexia and increased REE. The REE levels are related to the underling respiratory disease.

Introduction: Deep brain stimulation (

Patients with hereditary sensory and autonomic neuropathy type III(HSAN III) exhibit marked gait disturbances. The cause of the gaitataxia is not known, but we recently showed that functional musclespindle afferents in the leg, recorded via intraneural microelectrodesinserted into the peroneal nerve, are absent in HSAN III, althoughlarge-diameter cutaneous afferents are intact. Moreover, there is atight correlation between loss of proprioceptive acuity at the knee andthe severity of gait impairment. Here we tested the hypothesis thatmanual motor performance is also compromised in HSAN III,attributed to the predicted absence of muscle spindles in the intrinsicmuscles of the hand. Manual performance in the Purdue pegboardtask was assessed in 12 individuals with HSAN III and 12 age-matched healthy controls. The mean (+/- SD) pegboard score (number ofpins inserted in 30 s) was 8.1 +/- 1.9 and 8.6 +/- 1.8 for the left andright hand respectively, significantly lower than the scores for thecontrols (14.3 +/- 2.9 and 15.5 +/- 2.0; P <0.0001). In five patients weinserted a tungsten microelectrode into the ulnar nerve at the wrist.No spontaneous or stretch-evoked muscle afferent activity could beidentified in any of the 11 fascicles supplying intrinsic muscles of thehand, whereas rich tactile afferent activity could be recorded from 4cutaneous fascicles. We conclude that functional muscle spindles areabsent in the hand, and likely absent in the long finger flexors andextensors, and that this largely accounts for the poor manual motorperformance in HSAN III

Hereditary sensory and autonomic neuropathy type III (HSAN III)features a marked ataxic gait that progressively worsens over time.We recently assessed whether proprioceptive disturbances can explainthe ataxia. Proprioception at the knee joint was assessed using passivejoint angle matching in 18 patients and 14 age-matched controls; fivepatients with cerebellar ataxia were also studied. Ataxia was quantified using the Brief Ataxia Rating Score, which ranged from 7 to26/30. Patients with HSAN III performed poorly in judging jointposition at the knee: mean (+/- SE) absolute error was 8.7 +/- 1.0 andthe range was very wide (2.8-18.1); conversely, absolute error wasonly 2.7 +/- 0.3 (1.6-5.5) in the controls and 3.0 +/- 0.2 (2.1-3.4) in the cerebellar patients. This error was positively correlated tothe degree of ataxia in patients with HSAN III but not in patients withcerebellar ataxia. However, using the same approach at the elbowrevealed no significant differences in mean error in 12 patients withHSAN III (4.8 +/- 1.2; 3.0-7.2) and 12 age-matched controls(4.1 +/- 1.1; 2.1-5.5). Interestingly, microelectrode recordingsfrom the peroneal nerve showed a complete absence of spontaneousor stretch-evoked muscle afferent activity, confirmed in the ulnarnerve. Clearly, the lack of muscle spindles compromised proprioception at the knee but not at the elbow, and we suggest that patientswith HSAN III have learned to rely more on proprioceptive signalsfrom the skin around the elbow. Indeed, applying longitudinal stripsof elastic tape around the joint to increase tensile strain in the skinimproved proprioception at the knee but not the elbow