The fascination of complex regional pain syndrome.

Complex regional pain syndrome (CRPS) is a pain disorder involving the somatosensory, the somatomotor and the sympathetic nervous systems. Based on experiments conducted by Bove (2009), it is suggested that changes in impulse activity in small-diameter afferents and postganglionic axons generated by neuritis can contribute to signs of early CRPS. The potential mechanisms involved are discussed. These mechanisms include the possibility that CRPS, a disorder of the central nervous system, may be caused by a nerve inflammation.

Bilaterally symmetric form of Hirayama disease.

BACKGROUND: Hirayama disease (brachial monomelic amyotrophy) is a unilateral or grossly asymmetric bilateral disease. Bilaterally symmetric involvement has never been described. METHODS: Based on cardinal clinical and MRI criteria, a total of 106 patients with Hirayama disease from two tertiary care hospitals of North India seen between 1992 and 2008 formed the basis of this study. All those found to have bilaterally symmetric involvement on clinical and electrophysiologic basis were evaluated for clinical, electrophysiologic, and MRI correlates other than those required for the diagnosis. RESULTS: Eleven patients, who constituted around 10% of all the patients with Hirayama disease, were found to have bilaterally symmetric involvement. Nine of them had a history of unilateral onset. The important characteristics of this type of presentation included severe weakness and wasting in C7, C8, and T1 myotomes that frequently spilled over to C6 segment, predominant autonomic dysfunction in distal upper extremities in the form of cold paresis, cold skin, excessive sweating, and hair loss over the dorsum of the hands, and a very prominent bilateral minipolymyoclonus. MRI during complete flexion of neck showed severe flattening of lower cervical spinal cord against C5-C6 vertebral bodies and development of a crescent-shaped enhancing epidural space extending from C4 to T2 spine. CONCLUSION: Bilaterally symmetric Hirayama disease is a severe form of a classic disease which remains undiagnosed due to a common notion that it is a unilateral or grossly asymmetric disease. This description calls for review of the term "brachial monomelic amyotrophy" described to denote this disease.

Anhidrosis in multiple system atrophy: a preganglionic sudomotor dysfunction?

Anhidrosis occurs in the majority of multiple system atrophy (MSA) patients but the underlying site of lesion is not well established. We describe three patients with long-standing MSA and anhidrosis diagnosed on the basis of a thermoregulatory sweating test. In biopsies of anhidrotic skin, immunofluorescence analysis disclosed a well preserved postganglionic sudomotor innervation in all three patients supporting the hypothesis of a preganglionic nerve fiber lesion underlying their anhidrosis. Postganglionic sudomotor fiber integrity was also confirmed by normal electrodermal responses in one patient, whereas such responses and microneurographically detectable skin sympathetic nerve activity were absent in the other two MSA patients, suggesting a functional inactivity of structurally intact postganglionic sympathetic skin fibers.

Autonomic failure as the initial presentation of Parkinson disease and dementia with Lewy bodies.

The authors report the clinical and postmortem neuropathologic findings of two patients, one with Parkinson disease (PD) and one with dementia with Lewy bodies (DLB), both of whom initially sought treatment for isolated autonomic failure. These cases suggest that neurodegeneration in PD and DLB may begin outside the CNS in autonomic postganglionic neurons, a finding with potential diagnostic and therapeutic implications.

Hypercapnia induces long-term changes in postganglionic renal nerve activity in the piglet.

In developing swine, time and frequency domain analyses were used to compare changes in discharge features of efferent phrenic and postganglionic renal nerve activities evoked by prolonged (1 h) exposure to severe hypercapnia (10% CO2, balance O2), before and after combined carotid sinus and aortic depressor nerve (CSN-AOD) sectioning. With intact CSN-AOD innervation, respiration-related activity in renal nerve discharge was rare (3 of 11 animals) during baseline periods with intact innervation, but was observed in most cases (10 of 11 animals) during baseline following denervation. Renal nerve respiration-related activity was recruited by hypercapnic stimulation in animals with intact CSN-AOD innervation, and was augmented in denervated animals with ongoing respiratory activity. Phrenic nerve discharge was markedly augmented during hypercapnia, whether CSN-AOD innervation was intact or not, and it did not exhibit a post-hypercapnic depression. Autopower spectra of renal nerve activity revealed the presence of two coexisting rhythms, 2-6 and 7-13 Hz, which were present whether CSN-AOD innervation was intact or not. The hypercapnic-induced increases of activity in the 2-6 and 7-13 Hz bands were not comparable, with the latter region exhibiting a much more robust response to hypercapnia, especially following CSN-AOD denervation. Thus, prolonged exposure to hypercapnia evoked changes in renal nerve discharge that involved increased coupling to neuronal ensembles shaping central inspiratory activity and those generating central sympathetic outflows, especially to networks generating 7-13 Hz rhythm. Such changes may permit more efficient modulation of innervated structures during exposure to stressors.

Neurotransmitter specificity of sympathetic denervation in Parkinson's disease.

In PD, orthostatic hypotension reflects sympathetic noradrenergic denervation. The authors assessed sympathetic cholinergic innervation by the quantitative sudomotor axon reflex test (QSART) in 12 patients who had sympathetic neurocirculatory failure, markedly decreased cardiac 6-[18F] fluorodopamine-derived radioactivity, and subnormal plasma norepinephrine increments during standing. All 12 had normal QSART results. The sympathetic nervous system lesion in PD involves loss of postganglionic catecholaminergic but not cholinergic nerves.

Autonomic modification of the atrioventricular node during atrial fibrillation: role in the slowing of ventricular rate.

BACKGROUND: Postganglionic vagal stimulation (PGVS) by short bursts of subthreshold current evokes release of acetylcholine from myocardial nerve terminals. PGVS applied to the atrioventricular node (AVN) slows nodal conduction. However, little is known about the ability of PGVS to control ventricular rate (VR) during atrial fibrillation (AF). METHODS AND RESULTS: To quantify the effects and establish the mechanism of PGVS on the AVN, AF was simulated by random high right atrial pacing in 11 atrial-AVN rabbit heart preparations. Microelectrode recordings of cellular action potentials (APs) were obtained from different AVN regions. Five intensities and 5 modes of PGVS delivery were evaluated. PGVS resulted in cellular hyperpolarization, along with depressed and highly heterogeneous intranodal conduction. Compact nodal AP exhibited decremental amplitude and dV/dt and multiple-hump components, and at high PGVS intensities, a high degree of concealed conduction resulted in a dramatic slowing of the VR. Progressive increase of PGVS intensity and/or rate of delivery showed a significant logarithmic correlation with a decrease in VR (P<0.001). Strong PGVS reduced the mean VR from 234 to 92 bpm (P<0.001). The PGVS effects on the cellular responses and VR during AF were fully reproduced in a model of direct acetylcholine injection into the compact AVN via micropipette. CONCLUSIONS: These studies confirmed that PGVS applied during AF could produce substantial VR slowing because of acetylcholine-induced depression of conduction in the AVN.

Autonomic dysfunction in chronic intestinal pseudo-obstruction.

Fifteen tests were used to assess adrenergic, non-vagal cholinergic, and cardiovagal functions in 11 patients with chronic intestinal pseudo-obstruction (CIP). The three aims of this study were: 1) to ascertain the presence of and spectrum of autonomic involvement; 2) to assess the level of autonomic dysfunction; and 3) to compare the results of autonomic function tests with gastrointestinal motility patterns. Gastrointestinal motility displayed a neuropathic pattern in 10 patients. Adrenergic functions were abnormal in nine patients and non-vagal cholinergic functions in 10 patients. Cardiovagal functions were abnormal in only seven patients. The autonomic dysfunction was localized mostly to the postganglionic pathways. One patient, who had a myopathic pattern and muscle degeneration on small bowel biopsy, demonstrated normal responses to autonomic function tests. The patients with neuropathic CIP demonstrated widespread, mostly postganglionic autonomic dysfunction. Neuropathic CIP can occur with or without cardiovagal involvement.

Postganglionic cholinergic dysautonomia with incomplete recovery: a clinical, neurophysiological and immunological case study.

A 26-year-old man presented with signs and symptoms of marked postganglionic cholinergic autonomic dysfunction manifested by non-reacting dilated pupils, paresis of accommodation, decreased salivation, dry skin, atony of the bladder, erectile impotence and complete gastrointestinal paresis. Standard neurophysiological tests for myelinated sensory and motor fibre function and quantitative methods to examine unmyelinated parasympathetic, sympathetic and afferent fibres were performed: parasympathetic function was measured by heart rate variation tests. Sympathetic cutaneous vasoconstrictor responses induced by deep inspiration were examined with laser Doppler flowmetry. Cutaneous nociceptive C-fibre function was assessed by measurement of axon reflex vasodilatation and flare size induced by histamine iontophoresis. The findings confirmed that the abnormalities were restricted exclusively to the cholinergic postganglionic autonomic systems. All other functions were completely preserved. Modern neurophysiological methods of testing sympathetic and afferent small fibre function might help in the diagnosis of cholinergic postganglionic dysautonomia in the early stages. The specificity of the dysfunction argues in favour of an immunological pathogenesis. However, antibody screening including acetylcholine receptor antibodies and voltage-gated calcium channel antibodies gave negative results. Whatever autoimmunological mechanism might be involved, the postulated antibodies act highly specifically on unknown structures of the cholinergic postganglionic autonomic neurons.

Sudomotor dysfunction in amyotrophic lateral sclerosis.

We performed a quantitative sudomotor function test on 11 patients with classic amyotrophic lateral sclerosis (ALS) and 11 age-matched control subjects. Thermal warming increased the sweat rate in the forearm of ALS patients and in the forearm and thigh of control subjects. The sweat rate in the thigh of ALS patients was lower than that of controls. Thyrotropin releasing hormone increased the sweat rate in the forearm and thigh and decreased oral temperature in both ALS and controls but the lower extremity response was reduced in ALS. Results of the sudomotor axon reflex test on the thigh indicate that in ALS, there is mild postganglionic sudomotor dysfunction. We conclude that patients with ALS have mild thermoregulatory sweat dysfunction due to postganglionic lesions in the lower extremities.

Pure progressive autonomic failure: a clinicopathological study.

Two cases of pure progressive autonomic failure (PAF) are presented. A postmortem study of one case (case 2) showed a pathology resembling that of Parkinson's disease. Marked cell loss was noted in the substantia nigra, nucleus ceruleus, and intermediolateral column of the spinal cord, while cell loss in the sympathetic ganglion was not remarkable. This case may be an exceptionally rare case of late-onset PAF in which autonomic failure was mainly ascribed to preganglionic (and central) pathology, although autonomic function tests suggested postganglionic sympathetic disorder in both cases.

[Disorders of autonomic fibers of the peripheral nerves in polyneuropathies]. / Porazhenie vegetativnykh volokon perifericheskikh nervov pri polinevropatiiakh.

The conditions of postganglionic fibers and parasympathetic fibers of vagus nerve were studied in 102 patients with varioustypes of polyneuritis and in 43 healthy individuals. In the control group the amplitude of evoked cutaneous sympathetic potential (ECSP) on the hand was 330 +/- 102 microV with 1.42 +/- 0.12 s latency, on the foot 230 +/- 81.7 microV with 2.04 +/- 0.17 s latency. Respiration arrhythmia at rest amounted to 45 +/- 14.7 ms and in forced ventilation 80.6 +/- 28.5 ms. Substantial changes of ECSP parameters and heart periods are characteristics of polyneuropathies. The disorders are especially severe in axonal polyneuropathies of various genesis: hand ECSP amplitude decreased to M + 107.5 +/- 118.3 microV, foot ECSP M-61.9 +/- 79.2 microV. Latencies increased on hand to M-1.8 +/- 0.55 s and on foot to M-2.29 +/- 0.71 s. Heart periods are also changed: M-27.9 +/- 1.1 ms at rest, M-66.9 +/- 56.4 ms in forced ventilation. Demyelinating polynephropathies elicit less pronounced changes in ECSP and respiratory arrhythmia. No clear correlations were detected between heart periods or ECSP parameters and clinical signs.

Chronic idiopathic anhidrosis.

We describe the cases of eight patients with chronic idiopathic anhidrosis. These patients were heat intolerant and became hot, flushed, dizzy, dyspneic, and weak but did not sweat when the ambient temperature was high or when they exercised. Four patients had preganglionic sudomotor lesions and in the remaining 4 the lesion appeared to be postganglionic. The patients did not have orthostatic hypotension, other evidence of generalized autonomic failure, or symptomatic somatic neuropathy. One patient regained thermoregulatory sweat function and no patient's condition progressed to generalized autonomic failure. Chronic idiopathic anhidrosis appears to be distinctly different from other autonomic neuropathies that tend to carry much poorer prognoses.

Bladder dysfunction in distal autonomic neuropathy of acute onset.

A patient with cholinergic dysautonomia and a patient with pandysautonomia have each been investigated for disturbances of bladder and urethral function. Both patients suffered from an inability to develop or sustain a detrusor contraction, while retaining normal bladder sensation. Biopsy specimens of bladder muscle stained for acetylcholinesterase revealed a significant reduction in cholinergic nerves compared with controls; however, the prominent cholinergic subepithelial plexus was strikingly preserved. These findings lend support to the view that acetylcholinesterase-containing nerves in the bladder muscle are motor fibres responsible for detrusor contraction, while those located in the subepithelium are sensory in function. Urethral sphincter electromyography revealed no abnormality of individual motor units, confirming that motor unit integrity in this muscle is dependent upon somatic rather than autonomic innervation. In the patient with pandysautonomia the proximal urethra was incompetent, while in the patient with cholinergic dysautonomia the bladder neck remained closed, as in controls. This suggests that sympathetic rather than parasympathetic efferent activity is necessary for the maintenance of proximal urethral competence.

Loss of accommodation in sympathetic neurons from spontaneously hypertensive rats.

Synaptic transmission and membrane properties of sympathetic neurons in superior cervical ganglia of spontaneously hypertensive rats (SHR), normotensive Wistar-Kyoto rats (WKY), and Sprague-Dawley rats (SD) were investigated in vitro by extracellular and intracellular recording. The sympathetic neurons of SHR showed an atypical loss of spike accommodation. The spike discharge was insensitive to the sodium channel blocker tetrodotoxin, but it was reversibly blocked by a variety of calcium antagonists. The loss of accommodation in the neurons of SHR was not due to a loss of M-current, a potassium current involved in controlling spike frequency adaptation in sympathetic neurons. Superfusion of ganglia of SHR with muscarine (10 microM), which suppresses M-current and leads to a loss of accommodation, potentiated the repetitive discharge. In the presence of muscarine the current-voltage curves in neurons of SHR and SD were shifted to similar extents. Resting membrane potentials of neurons of SHR and WKY were consistently depolarized as compared with neurons of SD. Synaptic efficacy through the ganglia of SHR, assessed by extracellular recordings of presynaptic and postsynaptic compound action potentials at 0.25 Hz stimulation, was elevated when compared with the ganglia of WKY, but was similar to that of the ganglia of SD. These results indicate that strain differences should be considered when attempting to attribute changes in sympathetic neuron membrane properties to hypertension. The sympathetic neurons of SHR appear to have lost their accommodative properties and might possess an exaggerated calcium conductance. This calcium conductance may explain the augmented calcium-dependent release of norepinephrine during sympathetic nerve stimulation in the SHR.

Sympathetic nervous adjustments in man to simulated weightlessness induced by water immersion.

To clarify the role of the sympathetic nervous system to adjust the fluid shift under weightlessness, muscle and skin sympathetic activities were recorded microneurographically in human subjects under simulated weightlessness induced by water immersion up to the levels of the knee, the navel, the breast and the neck. The muscle and skin sympathetic activities were reduced in proportion to rise of immersion level up to the neck. These changes of sympathetic activities were almost concomitant with those of simultaneously recorded soleus electromyograms and heart rate. Reductions of the thigh and the leg circumference were also confirmed by strain gauge plethysmogram recorded under the same experimental condition. Based on these findings, it is concluded that the sympathetic nervous system is suppressed under weightlessness simulated by water immersion. This suppression might depend mainly on the activation of intrathoracic low pressure receptors, due to the fluid shift toward the upper part of the body. The suppression of the sympathetic nervous system seems to be important to compensate the fluid shift under weightlessness.