Loavenbruck, Adam

ObjectiveTo systematically compare transthyretin with primary amyloid neuropathy to define their natural history and the underlying mechanisms for differences in phenotype and natural history.MethodsAll patients with defined amyloid subtype and peripheral neuropathy who completed autonomic testing and electromyography at Mayo Clinic Rochester between 1993 and 2013 were included. Medical records were reviewed for time of onset of defined clinical features. The degree of autonomic impairment was quantified using the composite autonomic severity scale. Comparisons were made between acquired and inherited forms of amyloidosis.ResultsOne hundred one cases of amyloidosis with peripheral neuropathy were identified, 60 primary and 41 transthyretin. Twenty transthyretin cases were found to have Val30Met mutations; 21 had other mutations. Compared to primary cases, transthyretin cases had longer survival, longer time to diagnosis, higher composite autonomic severity scale scores, greater reduction of upper limb nerve conduction study amplitudes, more frequent occurrence of weakness, and later non‐neuronal systemic involvement. Four systemic markers (cardiac involvement by echocardiogram, weight loss > 10 pounds, orthostatic intolerance, fatigue) in combination were highly predictive of poor survival in both groups.InterpretationThese findings suggest that transthyretin has earlier and greater predilection for neural involvement and more delayed systemic involvement. The degree and rate of systemic involvement is most closely related to prognosis. Ann Neurol 2016;80:401–411

Abstract Background Gastrointestinal symptoms are common in the postural orthostatic tachycardia syndrome ( POTS ). However, few studies have evaluated gastrointestinal transit in POTS . Our primary objectives were to evaluate gastrointestinal emptying and the relationship with autonomic dysfunctions in POTS . Methods We reviewed the complete medical records of all patients aged 18 years and older with POTS diagnosed by a standardized autonomic reflex screen who also had a scintigraphic assessment of gastrointestinal transit at Mayo Clinic Rochester between 1998 and 2012. Associations between specific gastric emptying and autonomic (i.e., cardiovagal, adrenergic, and sudomotor) disturbances were evaluated. Key Results Among 163 patients (140 women, mean [± SEM ] age 30 [±1] years), 55 (34%) had normal, 30 (18%) had delayed, and 78 (48%) had rapid gastric emptying. Fifty‐eight patients (36%) had clinical features of physical deconditioning, which was associated ( p = 0.02) with rapid gastric emptying. Associations with delayed gastric emptying included vomiting, which was more common ( p < 0.003), and anxiety or depression, which was less common ( p = 0.02). The tilt‐associated increase in heart rate and reduction in systolic BP at 1 min was associated ( p < 0.05), being greater in patients with delayed gastric emptying. Conclusions & Inferences Two‐thirds of patients with POTS and GI symptoms had abnormal, most frequently rapid gastric emptying. Except for more severe adrenergic impairment in patients with delayed gastric emptying, the pattern of autonomic dysfunction did not discriminate among gastric emptying groups. Further studies are necessary to ascertain whether extravascular volume depletion and/or deconditioning contribute to POTS in patients with gastrointestinal symptoms.

ABSTRACTIntroduction: No study has correlated thermoregulatory sweat testing (TST) with histopathologic study of sweat glands (SGs) and SG nerve fibers (SGNFs). Methods: We studied 10 neuropathy patients in whom anhidrosis was found by TST and 10 matched controls. Skin biopsies were taken from both anhidrotic and sweating skin and immunohistochemical staining was done for nerves and basement membrane. For each biopsy, total tissue volume, total SG volume, and total SGNF length were measured. SGNF length per biopsy volume, SG volume per biopsy volume (SG%), and SGNF length per SG volume were calculated. Results: SGNF length per biopsy volume was reduced in anhidrotic site biopsies of patients compared with controls. SG% was decreased and SGNF length per SG volume increased in patients compared with controls. Conclusions: The results suggest a concomitant loss of SG volume and SGNF length in neuropathy, with greater loss of SGNFs in anhidrotic skin, possibly exceeding collateral reinnervation. Muscle Nerve 50: 528–534, 2014