Adam Loavenbruck

Disturbances of gastrointestinal transit and autonomic functions in postural orthostatic tachycardia syndrome

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.

Quantification of sweat gland volume and innervation in neuropathy: Correlation with thermoregulatory sweat testing

Introduction: 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

Neurogenic orthostatic hypotension: Roles of norepinephrine deficiency in its causes, its treatment, and future research directions

Abstract Background: Although a diversity of neurotransmitters and hormones participate in controlling blood pressure, norepinephrine released from postganglionic sympathetic nerve terminals is an important mediator of the rapid regulation of cardiovascular function required for homeostasis of cerebral perfusion. Hence, neurogenic orthostatic hypotension (NOH) often represents a deficiency of noradrenergic responsiveness to postural change. Research design and methods: PubMed searches with ‘orthostatic hypotension’ and ‘norepinephrine’ as conjoint search terms and no restriction on language or date, so as to survey the pathophysiologic and clinical relevance of norepinephrine deficiency for current NOH interventions and for future directions in treatment and research. Results: Norepinephrine deficiency in NOH can arise peripherally, due to cardiovascular sympathetic denervation (as in pure autonomic failure, Parkinson’s disease, and a variety of neuropathies), or centrally, due to a failure of viscerosensory signals to generate adequate sympathetic traffic to intact sympathetic nerve endings (as in multiple system atrophy). Nonpharmacologic countermeasures such as pre-emptive water intake may yield blood-pressure increases exceeding those achieved pharmacologically. For patients with symptomatic NOH unresponsive to such strategies, a variety of pharmacologic interventions have been administered off-label on the basis of drug mechanisms expected to increase blood pressure via blood-volume expansion or vasoconstriction. Two pressor agents have received FDA approval: the sympathomimetic midodrine and more recently the norepinephrine prodrug droxidopa. Conclusions: Pressor agents are important for treating symptomatic NOH in patients unresponsive to lifestyle changes alone. However, the dysautonomia underlying NOH often permits blood-pressure excursions toward both hypotension and hypertension. Future research should aim to shed light on the resulting management issues, and should also explore the possibility of pharmacotherapy selectively targeting orthostatic blood-pressure decreases.

Mass spectrometry analysis reveals non-mutated apolipoprotein a1 lumbosacral radiculoplexus amyloidoma

Introduction: In rare instances, amyloidosis presents as a focal, macroscopic lesion involving peripheral neural tissues (amyloidoma). In all known reported cases, peripheral nerve amyloidomas have had immunoglobulin light‐chain fibril composition and occurred in the context of paraproteinemia. Methods: A 46‐year‐old man presented with progressive insidious‐onset right lumbosacral radiculoplexus neuropathy without paraproteinemia. MRI‐targeted fascicular nerve biopsy was performed on an enlarged sciatic nerve after earlier distal fibular nerve biopsy was nondiagnostic. Laser dissected mass spectroscopy of the discovered amyloid protein was performed after immunohistochemistry failed to identify the specific amyloid protein. Complete gene sequencing of apolipoprotein A1 (ApoA1) was performed. Results: Only wild‐type ApoA1 amyloid was found in the congophilic component in the nerve. Conclusions: This case highlights the utility of MRI‐guided fascicular nerve biopsy combined with laser‐dissected mass spectrometric analysis. Importantly, the case expands the known causes of amyloidomas to include wild‐type ApoA1. Muscle Nerve 46: 817–822, 2012

Transthyretin amyloid neuropathy has earlier neural involvement but better prognosis than primary amyloid counterpart: an answer to the paradox?

To systematically compare transthyretin with primary amyloid neuropathy to define their natural history and the underlying mechanisms for differences in phenotype and natural history.

A device to measure secretion of individual sweat glands for diagnosis of peripheral neuropathy

There is a need for quantitative, precise assessment of small fiber peripheral nerve function. We tested a customized camera device and protocol designed to quantify secretions of individual sweat glands (SGs). Testing was performed on 178 healthy controls and 20 neuropathy subjects. Sweating was stimulated on a 2.25 cm2 skin area by iontophoresis of pilocarpine. The camera imaged sweat from 50 to 400 sweat ducts. We calculated secretion rate of individual SGs, total sweat volume, and number of secreting SGs at four body sites. Neuropathy subjects were tested at the two distal sites to demonstrate the devices capability to detect abnormal sudomotor function. Normal ranges were calculated for each body site. Neuropathy subjects had lower sweat rates per SG, lower total sweat, and lower SG density. The normal values decreased with advancing age, were lower in females, and differed between body sites. There was good agreement with repeat testing. The device provides reliable, precise quantitative measures of sweat secretion from single SGs for characterization of sudomotor nerve function in healthy control subjects and in subjects with known peripheral neuropathy. The test combines the capabilities of existing tests of sudomotor function while providing additional capabilities.

The role of skin biopsy in differentiating small-fiber neuropathy from ganglionopathy

We aimed to test the clinical utility of the leg:thigh intraepidermal nerve‐fiber (IENF) density ratio as a parameter to discriminate between length‐dependent small‐fiber neuropathy (SFN) and small‐fiber sensory ganglionopathy (SFSG) in subjects with signs and symptoms of small‐fiber pathology.

Emerging Subspecialties in Neurology: Autonomic disorders

Autonomic nervous system (ANS) dysfunction as a cause of disease is an increasingly recognized health problem, not only in the field of neurology, but also in cardiology, gastroenterology, endocrinology, urology, psychiatry, and primary care medicine. Patients may present with a myriad of symptoms including orthostatic intolerance, recurrent syncope, labile blood pressure, disorders of sweating and thermoregulation, neurogenic bladder, sexual dysfunction, gastrointestinal dysmotility, pupil abnormalities, and sleep disorders. These symptoms may, in turn, be a consequence of genetic (e.g., hereditary sensory and autonomic neuropathies, transthyretin amyloidosis), neurodegenerative (e.g., Parkinson disease [PD], multiple system atrophy [MSA]), autoimmune (e.g., autoimmune ganglionopathies), or acquired disorders (e.g., spinal cord lesions, type 2 diabetes). Although autonomic symptoms may be among the most debilitating features of these progressive conditions, they are often treatable. Autonomic disorders specialists require a comprehensive knowledge of the anatomy, physiology, and pharmacology of the ANS, understanding of the pathophysiology and management of acute and chronic autonomic conditions, and expertise in the performance and interpretation of clinical and laboratory evaluation of the ANS.

Peripheral Nerve Amyloidosis

Provided is an overview of the pathology, clinically defining features, and subcategorization of peripheral nerve amyloidosis. This condition is pathologically hallmarked by infiltrative amyloid deposition in varied peripheral neural tissue localizations with associated clinical manifestations. Peripheral nerve involvement is a frequent presenting feature of systemic amyloidosis (Kyle et al., Peripheral Neuropathies, Saunders, Philadelphia, PA, 2,427–2,451, 2005). As with other organ systems, the diagnosis of amyloid involvement of peripheral nerve is often delayed because the clinical features may mimic many varieties of peripheral neuropathy. Therefore, pathologic discovery of unsuspected amyloidosis is common. The particular amyloid protein can determine the clinical course and preferred treatment modality, as well as potentially alert patients to familial predisposition. Advances in laboratory technology, including most notably mass spectrophotometric evaluation of nerve, continue to improve the accuracy and sensitivity of amyloid subtyping (Adams, J Neurol 248(8), 2001; Benson and Kincaid, Muscle Nerve 36(4), 2007; Klein et al. Arch Neurol 68(2), 2011). Appropriate directed peripheral neural biopsy can therefore be instrumental in identifying the diagnosis providing the specific amyloid type, informing prognosis, and directing care in each case.