Sensory Axonal Excitability Research Articles

Strength-duration properties and excitability of motor and sensory axons across different target thresholds.

The present series of studies aimed to investigate the biophysical basis underlying differences in behavior between motor and sensory axons at different target response levels. In 24 healthy individuals, axonal excitability protocols measured strength-duration properties and latent addition across several axonal populations, with target amplitudes set at 10%, 20%, 40%, and 60%. Strength-duration time constants (SDTCs) were typically longer at lower target levels for both motor and sensory axons. Threshold change at 0.2 ms during assessment of latent addition, representing a persistent Na+ current (Nap), was higher in sensory axons. Passive membrane properties were not different across target levels. Significant relationships were evident between the threshold change at 0.2 ms and SDTC across all target levels for motor and sensory axons. These differences were explored using mathematical modeling of excitability data. With decreasing target size, as the internodal leak conductance increased in sensory axons, the Barrett-Barrett conductance decreased, whereas the hyperpolarization-activated cation current (Ih) channels became more depolarized. A similar pattern was observed in motor axons. As such, it was concluded that Nap was not responsible for the differences observed in SDTC between different target levels, although within specific target levels, Nap changes contributed to the variability of SDTC. This study provides a comprehensive assessment of Nap current, SDTC, and outlines key factors operating at different target levels in motor and sensory axons. Findings from the present study may point to the contributing factors of symptom development in human neuropathy.NEW & NOTEWORTHY This study provides a comprehensive assessment concerning the strength-duration behavior of motor and sensory axons at differing target levels of the compound nerve response. Strength-duration time constant was increased at lower target response levels particularly for sensory axons, whereas threshold change at 0.2 ms and passive membrane properties were not different. The results have established templates for axonal behavior in normal human axons, demonstrating altered adaptive responses, presumably secondary to different patterns of nerve activation.

Axonal Excitability Does Not Differ between Painful and Painless Diabetic or Chemotherapy-Induced Distal Symmetrical Polyneuropathy in a Multicenter Observational Study.

ObjectiveAxonal excitability reflects ion channel function, and it is proposed that this may be a biomarker in painful (vs painless) polyneuropathy. Our objective was to investigate the relationship between axonal excitability parameters and chronic neuropathic pain in deeply phenotyped cohorts with diabetic or chemotherapy‐induced distal symmetrical polyneuropathy.MethodsTwo hundred thirty‐nine participants with diabetic polyneuropathy were recruited from sites in the UK and Denmark, and 39 participants who developed chemotherapy‐induced polyneuropathy were recruited from Denmark. Participants were separated into those with probable or definite neuropathic pain and those without neuropathic pain. Axonal excitability of large myelinated fibers was measured with the threshold tracking technique. The stimulus site was the median nerve, and the recording sites were the index finger (sensory studies) and abductor pollicis brevis muscle (motor studies).ResultsParticipants with painless and painful polyneuropathy were well matched across clinical variables. Sensory and motor axonal excitability measures, including recovery cycle, threshold electrotonus, strength–duration time constant, and current–threshold relationship, did not show differences between participants with painful and painless diabetic polyneuropathy, and there were only minor changes for chemotherapy‐induced polyneuropathy.InterpretationAxonal excitability did not significantly differ between painful and painless diabetic or chemotherapy‐induced polyneuropathy in a multicenter observational study. Threshold tracking assesses the excitability of myelinated axons; the majority of nociceptors are unmyelinated, and although there is some overlap of the "channelome" between these axonal populations, our results suggest that alternative measures such as microneurography are required to understand the relationship between sensory neuron excitability and neuropathic pain. ANN NEUROL 2022;91:506–520

Differences in nerve excitability properties across upper limb sensory and motor axons

ObjectiveThe excitability of motor and sensory axons of the main upper limb nerves were compared to characterise the differences between nerves and provide a guide for future studies in human diseases with median neuropathy at the wrist. MethodsAxonal excitability studies were undertaken on median and ulnar motor (APB and ADM) and sensory axons (D2 and D5) and the superficial radial axons (D1) using a threshold tracking technique. ResultsCompared to the median, ulnar motor axons had reduced early depolarising threshold electrotonus (TEd40(10–20 ms) p = 0.02) and superexcitability (p = 0.03). The ulnar sensory axons required a stronger stimulus (p = 0.02) and had a larger rheobase (p = 0.02) than median axons, but were otherwise comparable. The superficial radial axons were “fanned-in” compared to median, and to a lesser degree ulnar axons, with greater resting I/V slope. Mathematical modelling of the radial and median sensory axons suggested that a 15.1% reduction in conductances between nodal and internodal compartments accounted for 82% of this discrepancy. ConclusionsThe excitability parameters of motor and sensory axons are most comparable between median and ulnar nerves. SignificanceThe present study demonstrates the feasibility of, and provides normative data for, axonal excitability recordings of the radial and ulnar nerves. We suggest the use of ulnar recordings as an alternative to the median nerve in the setting of compressive neuropathy at the wrist.

Influence of age and gender in the sensory nerve fibers excitability.

ObjectivesTo assess the influence of age and gender on sensory nerve axonal excitability parameters.MethodsThirty‐three healthy subjects (21 women) were included, with a mean age of 34.6 (range 21–76). Median sensory nerve excitability measurements (index finger) were performed using the TRONDNF nerve excitability protocol of the QTRAC program.ResultsPeak sensory nerve action potential (SNAP) amplitude was significantly higher among women (27.1 vs. 9.2 μV; p = .022), and strength–duration time constant (SDTC) was significantly higher in men (0.7 vs. 0.5; p = .011), not dependent on age. Greater age was negatively correlated with resting I/V slope, not dependent on gender (r = –0.4; p = .024). No other changes in excitability properties with increasing age were found.ConclusionsPhysiological features like as age and gender do not have a relevant impact on sensory nerve excitability measurements, which can have implications regarding pharmacological treatments.

Sensory and motor axonal excitability testing in early diabetic neuropathy

ObjectiveThe aim of the present study was to gain insight into the pathophysiology of diabetic polyneuropathy (DPN) and examine the diagnostic value of sensory and motor axonal excitability testing. MethodsOne hundred and eleven type 2 diabetics with and without DPN (disease duration: 6.36 ± 0.25 years) and 60 controls were included. All participants received a thorough clinical examination including Michigan Neuropathy Screening Instrument (MNSI) score, nerve conduction studies (NCS), and sensory and motor excitability tests. Patients were compared by the likelihood of neuropathy presence, ranging from no DPN (17), possible/probable DPN (46) to NCS-confirmed DPN (48). ResultsMotor excitability tests showed differences in rheobase and depolarizing threshold electrotonus measures between NCS-confirmed DPN group and controls but no changes in hyperpolarising threshold electrotonus or recovery cycle parameters. Sensory excitability showed even less changes despite pronounced sensory NCS abnormalities. There were only weak correlations between the above motor excitability parameters and clinical scores. ConclusionsChanges in excitability in the examined patient group were subtle, perhaps because of the relatively short disease duration. SignificanceLess pronounced excitability changes than NCS suggest that axonal excitability testing is not of diagnostic value for early DPN and does not provide information on the mechanisms.

Altered sensory nerve excitability in fibromyalgia

To investigate nerve excitability changes in patients with fibromyalgia and the correlation with clinical severity. We enrolled 20 subjects with fibromyalgia and 22 sex and age-matched healthy subjects to receive nerve excitability test and nerve conduction study to evaluate the peripheral axonal function. In the fibromyalgia cohort, the sensory axonal excitability test revealed increased superexcitability (%) (P=0.029) compared to healthy control. Correlational study showed a negative correlation between increased subexcitability (%) (r=-0.534, P=0.022) with fibromyalgia impact questionnaire (FIQ) score. Computer modeling confirmed that the sensory axon excitability pattern we observed in fibromyalgia cohort was best explained by increased Barrett-Barrett conductance, which was thought to be attributed to paranodal fast K+ channel dysfunction. The present study revealed that paranodal sensory K+ conductance was altered in patients with fibromyalgia. The altered conductance indicated dysfunction of paranodal fast K+ channels, which is known to be associated with the generation of pain.

Excitability of motor and sensory axons in multifocal motor neuropathy

ObjectiveTo assess excitability differences between motor and sensory axons of affected nerves in patients with multifocal motor neuropathy (MMN). MethodsWe performed motor and sensory excitability tests in affected median nerves of 20 MMN patients and in 20 age-matched normal subjects. CMAPs were recorded from the thenar and SNAPs from the 3rd digit. Clinical tests included assessment of muscle strength, two-point discrimination and joint position. ResultsAll MMN patients had weakness of the thenar muscle and normal sensory tests. Motor excitability testing in MMN showed an increased threshold for a 50% CMAP, increased rheobase, decreased stimulus-response slope, fanning-out of threshold electrotonus, decreased resting I/V slope, shortened refractory period, and more pronounced superexcitability. Sensory excitability testing in MMN revealed decreased accommodation half-time and S2-accommodation and less pronounced subexcitability. Mathematical modeling indicated increased Barrett-Barrett conductance for motor fibers and increase in internodal fast potassium conductance for sensory fibers. ConclusionsExcitability findings in MMN suggest myelin sheath or paranodal seal involvement in motor fibers and, possibly, paranodal detachment in sensory fibers. SignificanceExcitability properties of affected nerves in MMN differ between motor and sensory nerve fibers.

Changes in long term peripheral nerve biophysical properties in childhood cancer survivors following neurotoxic chemotherapy

ObjectiveIn the context of increasing numbers of childhood cancer survivors (CCS), this study aimed to enhance understanding of the biophysical basis for long term chemotherapy induced peripheral neuropathy from different chemotherapy agents in CCS. MethodsDetailed cross-sectional neurophysiological examination, using median nerve axonal excitability studies, alongside clinical assessments, in 103 long term CCS (10.5 ± 0.6 years post-treatment). ResultsCisplatin treated CCS (n = 16) demonstrated multiple sensory axonal excitability changes including increased threshold (P < 0.05), alterations in depolarising and hyperpolarising threshold electrotonus (P < 0.05) and reduction in resting and minimum IV slope (P < 0.01). Vincristine treated CCS (n = 73) were comparable to controls, except for prolonged distal motor latency (P = 0.001). No differences were seen in the non-neurotoxic chemotherapy group (n = 14). Abnormalities were more evident in the cisplatin subgroup with greater clinical neuropathy manifestations. ConclusionPersistent long term changes in axonal biophysical properties vary with different chemotherapy agents, most evident after cisplatin exposure. Longitudinal studies of nerve function during chemotherapy treatment are required to further evaluate these differences and their mechanistic basis. SignificanceThis study provides a unique biophysical perspective for persistent cisplatin related neurotoxicity in children, previously under recognised.

P43-T Axonal excitability findings in familial dyslipidemia

Background Cholesterol is one of the most important components of the myelin sheath. Schwann cells are responsible for myelinization of peripheral nerves. All situations that disrupt cholesterol metabolism in Schwann cells may affect channel dynamics on peripheral axons. Cholesterol entrance into the cell has been impaired due to genetic defects in apoproteins or its receptors in familial dyslipidemia patients. This is why we aimed to study the effects of this possible metabolic impairment on familial dyslipidemia patients. We have been investigated motor and sensorial axonal excitability parameters. Material and methods We have evaluated median nerve motor and sensory axonal excitability parameters of patients diagnosed with familial dyslipidemia or investigated for familial dyslipidemia according to National Lipid Association screening and Simon Broome criteria by using Q-trackS software and compared with control group. Results There was a statistically significant difference in the refractory period in 2 ms (p = 0.0429, p = 0.00281) when the familial dyslipidemia group and control group were compared in terms of both sensory and motor electrophysiological parameters. Conclusions In patients with familial dyslipidemia, we have found that the refractory period is shorter than the control group in both sensory and motor electrophysiological parameters of the median nerve. This finding may suggest that the median nerve axons in these patients are hyperpolarized state than normal. This study is supported by TUBITAK.

Ih contributes to increased motoneuron excitability in restless legs syndrome.

Restless legs patients complain about sensory and motor symptoms leading to sleep disturbances. Symptoms include painful sensations, an urge to move and involuntary leg movements. The responsible mechanisms of restless legs syndrome are still not known, although current studies indicate an increased neuronal network excitability. Reflex studies indicate the involvement of spinal structures. Peripheral mechanisms have not been investigated so far. In the present study, we provide evidence of increased hyperpolarization-activated cyclic nucleotide-gated (HCN) channel-mediated inward rectification in motor axons. The excitability of sensory axons was not changed. We conclude that, in restless legs syndrome, an increased HCN current in motoneurons may play a pathophysiological role, such that these channels could represent a valuable target for pharmaceutical intervention. Restless legs syndrome is a sensorimotor network disorder. So far, the responsible pathophysiological mechanisms are poorly understood. In the present study, we provide evidence that the excitability of peripheral motoneurons contributes to the pathophysiology of restless legs syndrome. In vivo excitability studies on motor and sensory axons of the median nerve were performed on patients with idiopathic restless legs syndrome (iRLS) who were not currently on treatment. The iRLS patients had greater accommodation in motor but not sensory axons to long-lasting hyperpolarization compared to age-matched healthy subjects, indicating greater inward rectification in iRLS. The most reasonable explanation is that hyperpolarization-activated cyclic nucleotide-gated (HCN) channels open at less hyperpolarized membrane potentials, a view supported by mathematical modelling. The half-activation potential for HCN channels (Bq) was the single best parameter that accounted for the difference between normal controls and iRLS data. A 6mV depolarization of Bq reduced the discrepancy between the normal control model and the iRLS data by 92.1%. Taken together, our results suggest an increase in the excitability of motor units in iRLS that could enhance the likelihood of leg movements. The abnormal axonal properties are consistent with other findings indicating that the peripheral system is part of the network involved in iRLS.

A unified model of the excitability of mouse sensory and motor axons.

Non-invasive nerve excitability techniques have provided valuable insight into the understanding of neurological disorders. The widespread use of mice in translational research on peripheral nerve disorders and by pharmaceutical companies during drug development requires valid and reliable models that can be compared to humans. This study established a novel experimental protocol that enables comparative assessment of the excitability properties of motor and sensory axons at the same site in mouse caudal nerve, compared the mouse data to data for motor and sensory axons in human median nerve at the wrist, and constructed a mathematical model of the excitability of mouse axons. In a separate study, ischaemia was employed as an experimental manoeuvre to test the translational utility of this preparation. The patterns of mouse sensory and motor excitability were qualitatively similar to human studies under normal and ischaemic conditions. The most conspicuous differences between mouse and human studies were observed in the recovery cycle and the response to hyperpolarization. Modelling showed that an increase in temperature in mouse axons could account for most of the differences in the recovery cycle. The modelling also suggested a larger hyperpolarization-activated conductance in mouse axons. The kinetics of this conductance appeared to be much slower raising the possibility that an additional or different hyperpolarization-activated cyclic-nucleotide gated (HCN) channel isoform underlies the accommodation to hyperpolarization in mouse axons. Given a possible difference in HCN isoforms, caution should be exercised in extrapolating from studies of mouse motor and sensory axons to human nerve disorders.

Excitability of sensory axons in amyotrophic lateral sclerosis

ObjectiveTo evaluate the excitability of sensory axons in patients with amyotrophic lateral sclerosis (ALS). MethodsComprehensive sensory nerve excitability studies were prospectively performed on 28 sporadic ALS patients, compared to age-matched controls. Sensory nerve action potentials were recorded from digit 2 following median nerve stimulation at the wrist. Disease severity was measured using motor unit number estimation (MUNE), the revised ALS Functional Rating Scale (ALSFRS-R) and the MRC scale. ResultsThere were no significant differences in standard and extended measures of nerve excitability between ALS patients and controls. These unchanged excitability measures included accommodation to long-lasting hyperpolarization and the threshold changes after two supramaximal stimuli during the recovery cycle. Excitability parameters did not correlate with MUNE, ALSFRS-R, APB MRC scale or disease duration. ConclusionsThis cross-sectional study has identified normal axonal membrane properties in myelinated sensory axons of ALS patients. Previously described sensory abnormalities could be the result of axonal fallout, possibly due to a ganglionopathy, or to involvement of central sensory pathways rostral to gracile and cuneate nuclei. SignificanceThese results demonstrate the absence of generalized dysfunction of the membrane properties of sensory axons in ALS in the face of substantial deficits in motor function.

5. Neurophysiological dysfunction in chemotherapy-treated patients: Comparison of different platinum analogues

Objective Chemotherapy-induced peripheral neuropathy is a prominent side effect of treatment with platinum-based chemotherapies cisplatin and oxaliplatin. Progressive abnormalities in sensory axonal excitability have been linked to neuropathy severity in oxaliplatin-treated patients, but not examined in cisplatin-treated patients. Methods Sensory axonal excitability studies were undertaken in median nerve. Neuropathy was assessed via total neuropathy score reduced (TNSr). Results Clinical severity of neuropathy was greater (TNSr: 6.9 ± 1.2) in oxaliplatin-treated patients (N = 16, Age: 57.1 ± 3 years, cumulative dose: 801 ± 63.5 mg/m 2 , median 6 months post-completion IQR: 4–12.5) than in cisplatin-treated patients (TNSr: 3.2 ± 0.6, p . 01 , N = 17, Age: 48.5 ± 4.3 years, cumulative dose: 316.5 ± 19.3 mg/m 2 , median 7 months post-completion IQR: 3–30.5). Cisplatin and oxaliplatin-treated patients demonstrated deficits in sensory nerve function compared to controls, with increased threshold change in excitability (TEh90-100 ms Cis: −128.7 ± 4.7%; Ox: −140.9 ± 5.9%; control: −116.6 ± 3.1%, p . 01 ) and reduced median sensory amplitudes (Cis: 24.4 ± 3.0 μ V; Ox: 15.7 ± 3.0 μ V; control: 43.9 ± 1.1 μ V, p . 01 ) with greater abnormalities in oxaliplatin-treated patients ( p . 01 ). TEh90-100 ms was correlated to median amplitude (r = .418, p . 05 ), with patients demonstrating greater excitability abnormalities also demonstrating greater reduction in sensory amplitude. Conclusions Changes in axonal excitability parameters are consistent between platinum-based chemotherapies and linked to neuropathy severity. Significance Platinum analogues demonstrate similar pathophysiological mechanisms of nerve dysfunction. Axonal excitability techniques may provide a marker of axonal dysfunction across different platinum chemotherapies.

11. Studying human neurophysiology using the mouse tail!

Introduction Non-invasive threshold-tracking techniques have been used in vivo to probe the biophysical basis of many neuromuscular conditions in human subjects. However, there are ethical and practical limitations to the study of human subjects, and mouse models provide an alternative and complementary path. Transgenic mouse models and the use of mice during drug development make them attractive targets for axonal excitability studies. Aims The objective of this study was to develop a mouse model that would allow the valid comparison of the excitability of both motor and sensory axons in mice to that of humans. Methods Axonal excitability studies were performed in mice by stimulating at the base of the tail using non-polarisable Ag/AgCl ring electrodes and recording CMAP and SNAP responses distally using platinum needle electrodes. The results were compared to human studies, and a mathematical model of the excitability of mouse axons was developed. Results Forty-nine threshold-tracking studies were performed in mice aged 16–20 weeks with no adverse outcomes (30 M/19F). The excitability waveforms of mice were qualitatively similar to those recorded from human median nerve at the wrist. Mathematical modelling suggested that mouse and human axons are structurally similar, and that the differences are due to smaller Na+, larger fast K+, smaller slow K+ and larger hyperpolarization-activated currents. Conclusions Motor and sensory excitability studies are readily achievable in mature mice. The results and modelling suggest that, while there are quantitative differences in mouse and human axons, structurally the same channels and morphology underlie their excitability. As is the case in human studies on median nerve at the wrist, the mouse tail provides a valid model of axonal excitability, and this allows the assessment of motor and sensory function. This technique and the mathematical model should be useful for translational studies.

Hyperpolarization-activated cyclic-nucleotide-gated channels potentially modulate axonal excitability at different thresholds.

Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels mediate differences in sensory and motor axonal excitability at different thresholds in animal models. Importantly, HCN channels are responsible for voltage-gated inward rectifying (Ih) currents activated during hyperpolarization. The Ih currents exert a crucial role in determining the resting membrane potential and have been implicated in a variety of neurological disorders, including neuropathic pain. In humans, differences in biophysical properties of motor and sensory axons at different thresholds remain to be elucidated and could provide crucial pathophysiological insights in peripheral neurological diseases. Consequently, the aim of this study was to characterize sensory and motor axonal function at different threshold. Median nerve motor and sensory axonal excitability studies were undertaken in 15 healthy subjects (45 studies in total). Tracking targets were set to 20, 40, and 60% of maximum for sensory and motor axons. Hyperpolarizing threshold electrotonus (TEh) at 90-100 ms was significantly increased in lower threshold sensory axons times (F = 11.195, P < 0.001). In motor axons, the hyperpolarizing current/threshold (I/V) gradient was significantly increased in lower threshold axons (F = 3.191, P < 0.05). The minimum I/V gradient was increased in lower threshold motor and sensory axons. In conclusion, variation in the kinetics of HCN isoforms could account for the findings in motor and sensory axons. Importantly, assessing the function of HCN channels in sensory and motor axons of different thresholds may provide insights into the pathophysiological processes underlying peripheral neurological diseases in humans, particularly focusing on the role of HCN channels with the potential of identifying novel treatment targets.NEW & NOTEWORTHY Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels, which underlie inward rectifying currents (Ih), appear to mediate differences in sensory and motor axonal properties. Inward rectifying currents are increased in lower threshold motor and sensory axons, although different HCN channel isoforms appear to underlie these changes. While faster activating HCN channels seem to underlie Ih changes in sensory axons, slower activating HCN isoforms appear to be mediating the differences in Ih conductances in motor axons of different thresholds. The differences in HCN gating properties could explain the predilection for dysfunction of sensory and motor axons in specific neurological diseases.

In vivo evidence of reduced nodal and paranodal conductances in type 1 diabetes

ObjectivesDiabetic neuropathy is a debilitating complication of diabetes. Animal models of type 1 diabetes (T1DM) suggest that functional and structural changes, specifically axo-glial dysjunction, may contribute to neuropathy development. The present study sought to examine and characterise early sensory axonal function in T1DM patients in the absence of clinical neuropathy. MethodsThirty patients with T1DM (15M:15F) without neuropathy underwent median nerve sensory and motor axonal excitability studies to examine axonal function. A verified mathematical model of human motor and sensory axons was used to elucidate the underlying causes of observed alterations. ResultsCompared to controls (NC), T1DM patients demonstrated significant axonal excitability abnormalities in sensory and motor axons. These included marked reductions in sensory and motor subexcitability during the recovery cycle (T1DM 7.9±0.4:10.4±0.6%, NC 10.4±0.7:15.4±1.2%, P<0.01) and during hyperpolarizing threshold electrotonus at 10–20ms (T1DM −75.5±0.8:−69.7±0.8%, NC −78.4±1:−72.7±0.9%, P<0.01). Mathematical modelling demonstrated that these changes were due to reduced nodal Na+ currents, nodal/paranodal K+ conductances and Na+/K+ pump dysfunction, consistent with axo-glial dysjunction as outlined in animal models of T1DM. ConclusionsThe study provided support for the occurrence of early changes in nodal and paranodal conductances in patients with T1DM. SignificanceThese data indicate that axonal excitability techniques may detect early changes in diabetic patients, providing a window of opportunity for prophylactic intervention in T1DM.

Age-dependent effects on sensory axonal excitability in normal mice

Serial recordings were performed to measure sensory excitability in peripheral nerves and elucidate age-dependent changes in neuronal ion currents in the peripheral sensory nervous system. The threshold tracking technique was used to measure multiple excitability indices in the tail sensory nerves of five normal male mice at four time points (6, 10, 14, and 19 weeks of age). A separate group of four mice was also measured at 43 weeks and at 60 weeks of age. Maturation was accompanied by an increase in early hyperpolarization and superexcitability at 10 weeks. At 60 weeks, the hyperpolarizing electrotonus shifted downward, while superexcitability became greater and subexcitability (double stimuli) decreased. Computer modeling showed that the most notable age-related interval changes in excitability parameters were Barrett–Barrett, H, and slow K+ conductances. Understanding age-related changes in the excitability of sensory axons may provide a platform for understanding age-dependent sensory symptoms and developing age-specific channel-targeting therapies.

76.: Clinical improvement of complex regional pain syndrome accompanied by reduced peripheral nerve excitability following intravenous immunoglobulin

Complex regional pain syndrome (CRPS) is a painful, debilitating and chronic condition. There is neither a disease-modifying treatment nor an objective test for the syndrome. A 32-year-old woman had features of CRPS in one arm following oropharyngeal herpes simplex virus-2 (HSV-2) infection. There was hyperaemia on bone scan during the delayed phase and a positive tilt table test. Autoantibodies were sought due to a known immune diathesis including novel neural antibodies using immunohistochemistry on rat tissue. Nerve excitability tests were performed acutely and at 6months. Immunoglobulin G (IgG) against spinal cord and dorsal root axons was found in this case but none of 10 controls with multiple sclerosis. The pattern was cytosolic and vesicular with sparing of the nodes of Ranvier. There was a demonstrable reduction in the excitability of peripheral median nerve motor and sensory axons with immunological treatments (intravenous [IV] IgG and immune suppressants). This case demonstrates an unusual aetiology of CRPS associated with autoimmunity and systemic autonomic dysfunction. Peripheral nerve excitability shows the effect of IVIg may be to reduce the excitability of neurons and possibly therefore central sensitization.

Sensory axonal dysfunction in cervical radiculopathy

ObjectiveThe aim of this study was to evaluate changes in sensory axonal excitability in the distal nerve in patients with cervical radiculopathy.MethodsThe patients were classified by the findings of cervical...

Brainstem reflexes in patients with familial dysautonomia

ObjectiveSeveral distinctive clinical features of patients with familial dysautonomia (FD) including dysarthria and dysphagia suggest a developmental defect in brainstem reflexes. Our aim was to characterize the neurophysiological profile of brainstem reflexes in these patients. MethodsWe studied the function of sensory and motor trigeminal tracts in 28 patients with FD. All were homozygous for the common mutation in the IKAP gene. Each underwent a battery of electrophysiological tests including; blink reflexes, jaw jerk reflex, masseter silent periods and direct stimulation of the facial nerve. Responses were compared with 25 age-matched healthy controls. ResultsAll patients had significantly prolonged latencies and decreased amplitudes of all examined brainstem reflexes. Similar abnormalities were seen in the early and late components. In contrast, direct stimulation of the facial nerve revealed relative preservation of motor responses. ConclusionsThe brainstem reflex abnormalities in FD are best explained by impairment of the afferent and central pathways. A reduction in the number and/or excitability of trigeminal sensory axons is likely the main problem. SignificanceThese findings add further evidence to the concept that congenital mutations of the elongator-1 protein (or IKAP) affect the development of afferent neurons including those carrying information for the brainstem reflex pathways.