Identification of corneal and intra-epidermal axonal swellings in amyotrophic lateral sclerosis.

INTRODUCTION/AIMS: In patients with amyotrophic lateral sclerosis (ALS), axonal spheroids in motor axons have been identified in post-mortem studies. In this study, axonal spheroids and swellings on C-fibers of ALS patients were investigated using corneal confocal microscopy (CCM) and skin biopsy, respectively. METHODS: Thirty-one ALS patients and 20 healthy subjects were evaluated with CCM to assess corneal nerve-fiber length (CNFL), -fiber density (CNFD), -branch density (CNBD), dendritic cell (DC) density, and axonal spheroids originating from C-fibers (>100 µm2 ). In addition, intraepidermal nerve fiber density (IENFD) and axonal swellings (>1.5 µm) were assessed in skin biopsies obtained from the arms and legs of 22 patients and 17 controls. RESULTS: In ALS patients, IENFD, CNFD, CNFL, and CNBD were not different from controls. The density of DCs and the number of patients with increased DC density were higher in ALS patients than controls (p = .0005 and p = .008). The number of patients with axonal spheroids was higher than controls (p = .03). DISCUSSION: Evaluation of DCs and axonal bulbs in C-fibers of ALS patients could provide insights into pathophysiology or potentially serve as biomarkers in ALS.

Single motor unit estimation of the cutaneous silent period in ALS.

OBJECTIVE: Recent evidence indicated that amyotrophic lateral sclerosis (ALS) also impairs spinal circuits, including those mediating cutaneous silent period (CSP). However, most studies utilised surface electromyography (sEMG), which needs more resolution to pinpoint changes at the single motoneuron level. We aimed to investigate CSP properties using single motor unit discharges in ALS. METHODS: In mild and severe ALS patients and controls, CSP was recorded in the first dorsal interosseus and analysed using the discharge rate method, which accurately shows the inhibitory postsynaptic potentials (IPSPs) profile. RESULTS: Our findings confirmed that the CSP latency was prolonged only in severe ALS patients. Moreover, the CSP duration was similar in each group, but late-stage ALS patients tend to have a longer CSP duration. The discharge rate method revealed a significantly longer duration (up to 150 ms) than the duration detected using sEMG. Strikingly, the motoneuron discharge rate - IPSP duration inverse relationship is lost in ALS patients, indicating a possible impairment in the motoneuron integrative properties. CONCLUSIONS: Our data support previous findings of prolonged latency, presented input-output modifications of motoneurons, and revealed the entire course of the CSP, representing a much stronger inhibitory event than previously thought. SIGNIFICANCE: Motoneuron integrative property modification assessed by CSP could be a new biomarker for ALS.

Stereological and electrophysiological evaluation of autonomic involvement in amyotrophic lateral sclerosis.

OBJECTIVE: Previous studies have identified autonomic dysfunction in amyotrophic lateral sclerosis (ALS) using mostly neurophysiological techniques. In this study, stereological evaluation of autonomic fibers and sweat glands has been performed to identify structural evidence of autonomic denervation in patients with ALS. METHODS: In this study, 29 ALS patients were compared to 29 controls using COMPASS-31 questionnaire, sympathetic skin response (SSR), and heart rate variability (HRV) at rest. From the same cohorts, 20 ALS patients and 15 controls were further evaluated using staining of autonomic nerve fibers and sweat glands in skin biopsies. SSR and resting HRV were repeated in the ALS patient cohort one year later. RESULTS: COMPASS-31 total score, gastrointestinal- and urinary-sub scores were higher in ALS patients than controls (P = 0.004, P = 0.005, and P = 0.049, respectively). In the ALS patient cohort, SSR amplitudes in hands and feet were lower than in controls (P<0.0001 and P = 0.0009, respectively), but there was no difference in resting HRV (P>0.05). While there was no change in nerve fibers innervating sweat glands, their density was lower in ALS patients than controls, and semi-quantitative analysis also showed structural damage (P = 0.02 and P = 0.001, respectively). SSR and resting HRV of ALS patients remained stable during the one-year follow-up period (P>0.05). DISCUSSION: Supporting abnormal neurophysiological tests, stereological analysis revealed direct evidence of autonomic denervation in ALS patients. However, the degenerative process in autonomic nerve fibers is relatively slow, compared to the rate of motor neuron degeneration in this condition.

Neurophysiologic assessment of small fibre damage in chemotherapy-induced peripheral neuropathy.

OBJECTIVE: In patients with chemotherapy-induced peripheral neuropathy (CIPN), demonstration of small fibre (SF) damage is important to understand chronic late effects. METHODS: Thirty patients having complaints compatible with possible CIPN following treatment with oxaliplatin or docetaxel were compared with 27 healthy subjects. All subjects were evaluated with quantitative sensory testing (QST) assessing SF function and laser evoked potentials (LEP). In addition, SF-damage was assessed using cutaneous silent periods evoked with electrical (El-CSP) and laser (Ls-CSP) stimuli. RESULTS: For LEP, N2P2 amplitudes were significantly smaller in patients than controls in both upper (P = 0.007) and lower extremities (P = 0.002), and the N1 amplitude in upper extremities of patients were significantly smaller than in controls (P = 0.001). SF-QST, LEP, Ls-CSP, and El-CSP were abnormal in 10 (33.3%), 16 (53.3%), 19 (63.3%), and 24 (80%) of CIPN patients, respectively. CONCLUSIONS: In patients with possible CIPN, El-CSP and Ls-CSP were more often abnormal than LEP and QST. This is probably because El-CSP and Ls-CSP inform mainly about peripheral nociceptive fibres, while LEP and QST inform about peripheral and central nociceptive pathways together. SIGNIFICANCE: LEP and QST are established methods to detect SF-damage. El- and Ls-CSP might help clinicians in diagnosing SF-damage.

Intrarater and Interrater Reliability of Heckmatt Scoring System in Amyotrophic Lateral Sclerosis.

PURPOSE: This study aims to determine the intrarater and interrater reliability of the Heckmatt score in the upper extremity muscles in patients with amyotrophic lateral sclerosis and to investigate its relationship with the clinical features and quantitative echo intensity measurements. METHODS: The Heckmatt scores of multiple upper extremity muscles were calculated in 28 patients with amyotrophic lateral sclerosis and examined the relationships of these values with quantitative ultrasound (QUS) measurements and the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised. RESULTS: The Heckmatt scores showed strong intrarater and interrater correlations with Cohen's Kappa scores ranging from 0.7 to 0.91. In all investigated muscles, the Heckmatt scores showed moderate correlations with quantitative echo intensity measurements and Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised dressing subscale. CONCLUSIONS: The Heckmatt score is a reliable method in evaluating muscles of the upper extremities in patients with amyotrophic lateral sclerosis. It moderately correlates with quantitative values and functional status.

Use of CMAP, MScan fit-MUNE, and MUNIX in understanding neurodegeneration pattern of ALS and detection of early motor neuron loss in daily practice.

BACKGROUND: The pattern of lower motor neuron (LMN) degeneration in amyotrophic lateral sclerosis (ALS), i.e., dying-back (from the nerve ending to cell body) or dying-forward (from the cell body to nerve ending), has been widely discussed. In this study, we aimed to evaluate LMN loss using compound muscle action potential (CMAP), motor unit number index (MUNIX), and MScan-fit-based motor unit number estimation (MUNE) to understand the pattern of neurodegeneration in ALS. METHODS: Twenty-five patients were compared with 25 controls using CMAP amplitude and area, MUNIX, and MScan-fit MUNE in three proximal and distal muscles innervated by the ulnar nerve. RESULTS: Unlike the controls, the CMAP area, MScan-fit MUNE, and MUNIX recorded in ALS patients showed more neurodegeneration in distal muscles than proximal muscles. In ALS patients with unaffected CMAP amplitudes (n = 13), the CMAP area, MScan-fit MUNE, and MUNIX showed subtle motor unit loss of 30.7 %, 53.8 %, and 38.4 %, respectively. CONCLUSION: The CMAP area, MScan-fit MUNE, and MUNIX showed neurodegeneration earlier than the reduction in CMAP amplitude. These tests confirmed dying-back neurodegeneration, while only MUSIX showed re-innervation in ALS.

Amyotrophic lateral sclerosis weakens spinal recurrent inhibition and post-activation depression.

OBJECTIVES: Amyotrophic lateral sclerosis (ALS) disrupts motoneurons that control movement and some vital functions, however, exact details of the neuronal circuits involved in ALS have yet to be fully endorsed. To contribute to our understanding of the responsible neuronal circuits, we aimed to investigate the spinal recurrent inhibition (RI) and post-activation depression (P-AD) in ALS patients. METHODS: In two groups of ALS patients, i.e. lumbar-affected (clinical signs in leg muscles) and nonlumbar-affected (clinical signs in arms or bulbar region but not in the legs), RI and P-AD on the soleus muscle were investigated using single motor units and amplitude changes of H-reflex in surface electromyography, respectively. The data were compared with healthy subjects. RESULTS: Compared to controls, P-AD of H-reflex was reduced severely in lumbar-affected patients and reduced to a certain degree in nonlumbar-affected patients. Similarly, a significant reduction in the duration of RI on firing motoneurons was found in lumbar-affected patients (11.5 ± 2.6 ms) but not in nonlumbar-affected patients (29.7 ± 12.4 ms, P < 0.0001) compared to controls (30.8 ± 7.2 ms, P < 0.0001). CONCLUSION: The current study revealed that spinal inhibitory circuits are impaired in ALS. SIGNIFICANCE: These findings may provide insight for proposing new therapeutic approaches and following disease progression in humans.

Revisiting the complex architecture of ALS in Turkey: Expanding genotypes, shared phenotypes, molecular networks, and a public variant database.

The last decade has proven that amyotrophic lateral sclerosis (ALS) is clinically and genetically heterogeneous, and that the genetic component in sporadic cases might be stronger than expected. This study investigates 1,200 patients to revisit ALS in the ethnically heterogeneous yet inbred Turkish population. Familial ALS (fALS) accounts for 20% of our cases. The rates of consanguinity are 30% in fALS and 23% in sporadic ALS (sALS). Major ALS genes explained the disease cause in only 35% of fALS, as compared with ~70% in Europe and North America. Whole exome sequencing resulted in a discovery rate of 42% (53/127). Whole genome analyses in 623 sALS cases and 142 population controls, sequenced within Project MinE, revealed well-established fALS gene variants, solidifying the concept of incomplete penetrance in ALS. Genome-wide association studies (GWAS) with whole genome sequencing data did not indicate a new risk locus. Coupling GWAS with a coexpression network of disease-associated candidates, points to a significant enrichment for cell cycle- and division-related genes. Within this network, literature text-mining highlights DECR1, ATL1, HDAC2, GEMIN4, and HNRNPA3 as important genes. Finally, information on ALS-related gene variants in the Turkish cohort sequenced within Project MinE was compiled in the GeNDAL variant browser (www.gendal.org).

Chronic Pain and Neuropathy Following Adjuvant Chemotherapy.

Objective: To determine symptoms and characteristics of chronic sensory neuropathy in patients treated with oxaliplatin and docetaxel, including patterns of somatosensory abnormalities, pain descriptors, and psychological functioning. Design: A retrospective cross-sectional study. Setting: A chronic pain research center. Subjects: Thirty-eight patients with chronic peripheral pain and/or dysesthesia following chemotherapy. Methods: Sensory profiles, psychological functioning, and quality of life were assessed using standardized questionnaires. In addition, standardized quantitative sensory testing and nerve conduction studies were carried out. Results: The sensory profiles and clinical symptoms were very similar in the two groups. Pricking, numbness, and burning were common descriptors in both groups, and the predominant finding was sensory loss to A beta-mediated sensory modalities with decreased mechanical and vibration detection thresholds. A high frequency of abnormalities in thermal sensory limen and the presence of paradoxical heat sensation seem to be sensitive markers of small fiber loss. Both groups had mainly sensory, axonal large fiber or mixed fiber polyneuropathy, which tended to be most severe in the oxaliplatin group. Conclusions: Both oxaliplatin-induced and docetaxel-induced polyneuropathies represent a significant problem that affects the daily life of the patients. Our results, defining the somatosensory phenotype, can improve the understanding of the pathophysiological mechanisms useful for future studies in the tailored treatment of prevention of chemotherapy-induced peripheral neuropathy and pain.

Diagnostic utility of distal nerve conduction studies and sural near-nerve needle recording in polyneuropathy.

OBJECTIVE: The electrodiagnosis of polyneuropathy (PNP) may benefit from examination using near-nerve needle technique (NNT) and from inclusion of distal nerves. This study compared the diagnostic utility of distal nerve conduction studies (NCS) and NNT recording. METHODS: Bilateral NNT and surface recording of the sural nerve and surface recording of the dorsal sural and medial plantar nerves were prospectively done in 91 patients with clinically suspected PNP. Distal NCS were additionally done in 37 healthy controls. Diagnostic reference standard was the final clinical diagnosis retrieved from the patients medical records after 1-4years. RESULTS: The clinical follow-up diagnosis confirmed PNP in 68 patients. Equally high sensitivities of the dorsal sural (72%), medial plantar (75%), and sural nerve with NNT recording (77%) were seen, while the sensitivity of conventional surface recording of the sural nerve was lower (60%). Sural NCS with both NNT and surface recording and dorsal sural NCS showed high specificities (85-95%) and positive predictive values (94-98%), while a lower specificity was seen for the medial plantar nerve (68%). CONCLUSION: NCS of distal nerves, especially the dorsal sural nerve, have high diagnostic power equalling sural NNT recording. SIGNIFICANCE: The electrodiagnostic evaluation of patients with suspected PNP benefits from NCS of distal nerves.

Quantitative sensory testing and structural assessment of sensory nerve fibres in amyotrophic lateral sclerosis.

OBJECTIVE: In this prospective study, involvement of sensory nerve fibres in ALS patients was assessed using functional and structural measures in the form of quantitative sensory testing (QST) and skin and nerve biopsies. METHODS: Thirty-two ALS patients and 32 healthy subjects were evaluated with a QST battery comprising thresholds of mechanical detection, mechanical pain, vibration detection, cold detection, warm detection, heat pain, and pinprick sensation. Skin biopsies were evaluated in 31 ALS patients by intraepidermal nerve fibre density (IENFD) and axonal swelling ratios, and growth-associated protein 43 (GAP-43) antibody staining. Sural nerve biopsies were evaluated using teased fibre analysis in eight patients. RESULTS: Mean values for QST parameters and IENFD in ALS patients were within normal range. However, the patients had increased axonal swelling ratios and GAP-43 antibody staining was negative in all patients. CONCLUSIONS: Although QST and IENFD were affected in only a small subset of ALS patients, the axonal swellings observed in all patients indicate that the affection is more frequent, and suggests that IENFD count may not be sufficient. The negative GAP-43 staining suggested an insufficiency of regeneration in small sensory nerve fibres.

Laser and somatosensory evoked potentials in amyotrophic lateral sclerosis.

OBJECTIVE: Mild involvement of sensory nerves has been reported in previous studies in ALS patients. In this study, we assessed sensory pathways in ALS patients using laser evoked potentials (LEPs) and somatosensory evoked potentials (SSEPs). METHODS: We recruited 18 ALS patients and 31 healthy subjects. Neodymium-doped yttrium aluminium perovskite (Nd:YAP)-laser was used to evoke LEPs in upper (UE) and lower (LE) extremities. N1 and N2P2 potentials were obtained from contralateral insular cortex (T3 or T4) and vertex (Cz), respectively. Median SSEPs were recorded from C3' or C4' and tibial SSEPs from Cz'. RESULTS: Compared to controls, ALS patients had longer N2 and P2 latencies, and smaller N2P2 amplitudes in both UE- and LE-LEPs (p<0.05), and longer latencies for median and tibial SSEPs (p<0.05). LEPs and SSEPs were abnormal in 72.2% and 56.6% patients, respectively. CONCLUSIONS: Cortical potentials showed that A-beta or A-delta sensory fibres, or both, were impaired in more than half of the ALS patients. SIGNIFICANCE: The findings support that ALS is a multi-systemic disorder involving, although to a lesser degree, other systems than the motor.

Involvement of distal sensory nerves in amyotrophic lateral sclerosis.

INTRODUCTION: The diagnostic criteria for amyotrophic lateral sclerosis (ALS) require normal sensory nerve conduction studies (NCS) or abnormal NCS only in the presence of neuropathy of identified etiology. In this study, we investigated the presence and extent of involvement of Aß sensory fibers in ALS. METHODS: Distal sensory NCS [antidromic dorsal sural (DS) and orthodromic medial plantar (MP)] and conventional sensory NCS (unilateral median sensory and bilateral sural nerves) were performed in 16 definite and 2 probable ALS patients (based on Awaji criteria) and 31 controls. RESULTS: Abnormal conventional sensory NCS were found in 8 (44.4%) ALS patients and 1 (3.2%) control subject (P = 0.002), whereas abnormal distal sensory NCS were found in 12 (66.7%) ALS patients and 3 (9.6%) controls (P < 0.0001). CONCLUSION: Distal sensory NCS were more often abnormal than conventional sensory NCS in ALS. Muscle Nerve 54: 1086-1092, 2016.

Palmar cutaneous nerve conduction in patients with carpal tunnel syndrome.

OBJECTIVE: This study aimed to assess palmar cutaneous branch of the median nerve (PCBm) conduction in patients with clinically diagnosed carpal tunnel syndrome (CTS), to compare PCBm conduction with that of the median and ulnar nerves, and to determine the PCBm conduction abnormality rate in patients with CTS. MATERIALS AND METHODS: The study included 99 hands of 60 patients with clinical CTS and 38 hands of 38 healthy controls. Sensory nerve conduction study (NCS) was performed on the median nerve, ulnar nerve, and PCBm, and onset latency, conduction velocity and amplitude were recorded. Additionally, differences in latency and velocity between the median nerve and PCBm, and the difference in latency between the median and ulnar nerves were calculated. RESULTS: In all, 56% of the patients with CTS had abnormal PCBm conduction. Additionally, in 7 of 8 hands with abnormal sensation--both in the thenar eminence and abnormal sensory distribution along the main branch--NCS of the PCBm was also abnormal. CONCLUSIONS: The PCBm is not ideal as a comparator nerve for the neurophysiological diagnosis of CTS. The frequency of PCBm abnormality in CTS patients may be related to the concomitant damage in both of these nerves. Additionally, the present findings may help explain, at least in part, why patients with CTS often exhibit sensory involvement beyond the classical median nerve sensory borders.

Cutaneous silent period recordings in demyelinating and axonal polyneuropathies.

OBJECTIVE: To investigate the cutaneous silent period (CSP), a spinal inhibitory reflex mainly mediated by A-delta fibres, in demyelinating and axonal polyneuropathy (PNP) and evaluate whether CSP parameters differ between patients with and without neuropathic pain. METHODS: Eighty-four patients with demyelinating PNP, 178 patients with axonal PNP and 265 controls underwent clinical examination, DN4 questionnaire, standard nerve conduction study, motor-root stimulation and CSP recordings from abductor digiti minimi. We calculated the afferent conduction time of CSP (a-CSP time) with the formula: CSP latency-root motor evoked potential latency. RESULTS: In the demyelinating PNP group the a-CSP time was significantly longer; in the axonal PNP group, CSP duration was shorter than the demyelinating group (p=0.010) and controls (p=0.001). CSP parameters were not different between patients with and without neuropathic pain. CONCLUSIONS: The abnormality of a-CSP time in the demyelinating PNP group suggests the crucial role of A-delta fibres in the mechanism of CSP; the shorter CSP duration in the axonal PNP group supports the strong influence of the number of axons on this parameter. Our study suggests that neuropathic pain could be related to pathophysiological mechanisms differing from mere A-delta fibre loss. SIGNIFICANCE: CSP evaluation is effective in detecting A-delta fibre dysfunction in axonal as well as demyelinating PNP.

Clinical utility of F wave parameters in unilateral S1 radiculopathy.

OBJECTIVE: To investigate the F wave parameters (F duration, F minimum latency, F maximum latency, F mean latency, F chronodispersion, and F persistence) of the tibial nerve with unilateral S1 radiculopathy. We evaluated the differences of these parameters between the affected and unaffected sides and also with the control group. METHODS: The study was performed from September 2007 to January 2008 in the Electrophysiology Laboratory of Marmara University Medical Faculty, Istanbul, Turkey. Bilateral tibial F waves were obtained from 20 normal control subjects (control group) and 20 patients with unilateral S1 radiculopathy (patient group). Minimum, maximum, and mean F latency values were corrected by the subject`s height (F min/H, F max/H, F mean/H). Needle electromyography was performed in the patient group. The patients with a history of diabetes, alcoholism, or other abnormality known to affect peripheral nerves were excluded. RESULTS: In the control group, no significant differences were found in any of the F-wave parameters between the 2 sides. In the patient group, there were significant prolongations of F duration, F min/H, F max/H, F mean/H, and F chronodispersion on the lesion side. Patients` F durations of the affected and unaffected side were significantly longer than the control group. The F chronodispersion also showed significant prolongation on the affected side in the patient group compared with the control group. Among 20 patients, 15 had evidence of denervation or polyphasic potentials on needle electromyography. CONCLUSION: The F wave study can be clinically useful in the evaluation of S1 radiculopathies, especially in patients with mild and early stage of the disease. Both F duration and F chronodispersion have a higher diagnostic value as compared to F min in the diagnosis of lumbosacral radiculopathy, especially in cases with normal findings on needle electromyography.

Assessment of symptomatic diabetic patients with normal nerve conduction studies: utility of cutaneous silent periods and autonomic tests.

Established electrophysiological methods have limited clinical utility in the diagnosis of small-fiber neuropathy (SFN). In this study, diabetic patients with clinically diagnosed SFN were evaluated with autonomic tests and cutaneous silent periods (CSPs). Thirty-one diabetic patients with clinically suspected SFN and normal nerve conduction studies were compared with 30 controls. In the upper extremities (UE), the CSP parameters did not differ statistically between the patient and control groups, whereas, in the lower extremities (LE), patients had prolonged CSP latencies (P = 0.018) and shortened CSP durations (P < 0.001). The sensitivity of the CSP duration was 32.6%, and the specificity was 96.7%. The expiration-to-inspiration ratios and amplitudes of the sympathetic skin responses in the lower extremities were also reduced. Our findings indicate that the diagnostic utility of CSPs was higher than that of the autonomic tests to support the clinically suspected diagnosis of SFN.

Where is the core of the volcano? The undetermined origin of primary restless legs syndrome.

An association between small fiber neuropathy and primary Restless Legs Syndrome (RLS) is suggested since both of them share common characteristics. Our aim was to investigate the existence of autonomic neuropathy on the basis of autonomic tests. The patients and the age-matched controls were evaluated with Neuropathy Symptom Profile and Autonomic Symptom Profile, nerve conduction studies (NCS), and autonomic tests. Patients suffered from neuropathic and autonomic complaints obviously. There was no significant difference for NCS, heart rate variability tests, and sympathetic skin responses (SSRs) among patients and controls. Since both the NCSs and the autonomic tests were within normal, the complaints were considered to be the consequences of the problem in sensory integration due to the dysfunction of the caudal diencephalic A11 group, rather than a neuropathic process. The cardiac autonomic imbalance possibly emerges as a consequence of arousal periods prior to or during the Periodic Leg Movements (PLM) episodes during sleep, but not due to autonomic neuropathy.

A neurophysiological approach to the complex organisation of the spine: F-wave duration and the cutaneous silent period in restless legs syndrome.

OBJECTIVE: It is generally accepted that F-wave duration (FWD) and the cutaneous silent period (CSP) are influenced by diminished central inhibition. The aim of this study was to diagnose patients of restless legs syndrome (RLS) with the help of FWD and/or CSP parameters. METHODS: In all, 24 patients with primary RLS were compared with 31 age- and sex-matched controls. The participants were evaluated based on nerve conduction study (NCS), F-wave parameters (minimum, maximum and mean latency; chronodispersion, persistence and duration; and the ratio of the mean FWD to compound muscle action potential (CMAP) duration), CSP (latency, duration and the ratio of lower-extremity (LE) to upper-extremity (UE) duration that is, silent period ratio (SPR)), the expiration to inspiration ratio (E/I) and sympathetic skin response (SSR). RESULTS: There were not any significant differences in NCS, E/I or SSR between the patients and controls. However, FWD was prolonged (P<0.0001 for UE and LE) and FWD/CMAP duration was increased in upper and lower extremities (P<0.001 for UE and P<0.0001 for LE). Further, CSP latencies in UE (P=0.030) and LE (P<0.001) were prolonged, and CSP duration and SPR were significantly reduced in the patient group (P<0.0001). CONCLUSIONS: As both NCS and autonomic test results were in the normal range, abnormalities in FWD and CSP parameters were attributed to the dysfunction of different interneuron groups in the spine. SIGNIFICANCE: The use of FWD and CSP could aid in the diagnosis of RLS patients in whom conventional electrophysiological procedures are ineffective.

Paraneoplastic pandysautonomia as a manifestation of non-small cell lung cancer.

Pandysautonomia is a severe and rare clinical condition characterized by widespread sympathetic and parasympathetic dysfunction. Consideration of whether symptoms and presentation are acute, subacute, or chronic is often helpful in establishing a differential diagnosis. The underlying mechanisms leading to pure pandysautonomia are unclear; however, there is some evidence suggestive of an immune-mediated pathogenesis. Herein, we report a case with pandysautonomia as a paraneoplastic manifestation of non-small cell lung cancer that had an excellent response to symptomatic and supportive treatments, as well as IVIG therapy.