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.

Psychophysiological and Neurophysiological Correlates of Dropping Objects from Hands in Carpal Tunnel Syndrome.

BACKGROUND: Dropping objects from hands (DOH) is a common symptom of carpal tunnel syndrome (CTS). We evaluated the clinical, neurophysiological, and psychophysiological features of 120 CTS patients to elucidate the DOH pathophysiology. Forty-nine healthy controls were included. METHODS: In the patients, the Boston Carpal Tunnel Questionnaire (BCTQ), the Douleur Neuropathique 4 questions (DN4), and a numeric rating scale for pain (NRS) were evaluated. In patients and controls, we evaluated bilateral median and ulnar motor and sensory nerve conduction studies, cutaneous silent period and cutaneomuscular reflexes (CMR) of the abductor pollicis brevis, cold-detection threshold (CDT) and heat-pain detection threshold (HPT) at the index, little finger, and dorsum of the hand, and vibratory detection threshold at the index and little finger by quantitative sensory testing. RESULTS: CTS with DOH had higher BCTQ, DN4 and NRS, lower median sensory action potential, longer CMR duration, lower CDT and higher HPT at all tested sites than controls and CTS without DOH. Predictive features for DOH were abnormal CDT and HPT at the right index and dorsum (OR: 3.88, p: 0.03) or at the little finger (OR: 3.27, p: 0.04) and a DN4 higher than 4 (OR: 2.16, p < 0.0001). CONCLUSIONS: Thermal hypoesthesia in median and extra-median innervated territories and neuropathic pain are predictive of DOH in CTS.

The cutaneous silent period as a measure of upper motor neuron dysfunction in amyotrophic lateral sclerosis.

OBJECTIVES: We investigated the cutaneous silent period (CutSP) as a measure of upper motor neuron (UMN) dysfunction in amyotrophic lateral sclerosis. METHODS: The onset latency, duration, and amount of EMG suppression of the CutSP were compared with clinical UMN signs in 24 patients with amyotrophic lateral sclerosis (ALS). UMN signs were quantified using a clinical index and transcranial magnetic stimulation (TMS). Central motor conduction time (CMCT), cortical motor threshold and motor evoked potential amplitudes were assessed as measures of UMN dysfunction. CutSP was studied in abductor digit minimi (ADM) and tibialis anterior (TA) EMG recordings following stimulation of the 5th finger and sural nerves respectively. Non-parametric tests and binomial logistic regression were applied to evaluate the data. RESULTS: CutSP onset latency was increased in ALS patients, compared to healthy controls, both for ADM and TA muscles. In limbs with clinical UMN signs or abnormal TMS findings, the CutSP onset latency was particularly increased. There was a significant positive correlation between CutSP onset latency and the UMN score in both upper and lower limbs. In TA muscles there was also a negative correlation between CutSP onset latency and EMG suppression. The logistic regression model based on CutSP parameters correctly classified more than 70% of the cases regarding the presence of clinical signs of UMN lesion, in both upper and lower limbs. The results were not significant for TMS. CONCLUSION: We conclude that upper limb CutSP changes associates with UMN lesion in ALS. This neurophysiological measurement merits further investigation in ALS.

Cutaneous silent period modulation by tooth clenching, tonic and phasic limb movements in healthy subjects.

OBJECTIVE: We aimed to examine the modulation of the cutaneous silent period (CSP) by tooth clenching and contralateral tonic dorsiflexion of lower limb and phasic voluntary movements of upper limb. METHODS: In 18 healthy subjects, we recorded CSP on right thenar muscle after painful stimulation of index finger during mild contraction at six conditions: baseline, maximum tooth clenching, contralateral tonic dorsiflexion of foot, as well as at the beginning (RT1), in the middle (RT2) and at last part (RT3) of the contralateral phasic wrist extension. We measured latency and duration and calculated suppression indices. RESULTS: During tooth clenching, the suppression index of second inhibitory phase (I2) was significantly higher than that at baseline condition. The suppression index of first inhibitory phase (I1) was reduced in tonic dorsiflexion. The I2 durations in RT2 and RT3 were longer than that at baseline. The I2 suppression indices during RT1, RT2, and RT3 were significantly higher than that at baseline condition (p < 0.05). CONCLUSION: The tooth clenching has an inhibitory effect on CSP. The contralateral phasic hand movements caused higher suppression index. The CSP is modulated by remote influences differently depending on the type of muscle contraction (tonic vs. phasic) and/or where it is realized (tooth, upper or lower limb).

The Silent Period for Small Fiber Sensory Neuropathy Assessment in a Mixed Cohort of Transthyretin-Mediated Amyloidosis.

BACKGROUND: Transthyretin-mediated amyloidosis (ATTR) is a rare multisystemic disease involving the peripheral nervous system and heart. Autonomic and small fiber involvement is one of the hallmarks of ATTR, and many tools have been proposed to assess this aspect. AIM: The aim of this study was to investigate cutaneous and mixed nerve silent periods (CSP and MnSP) as instruments for small fiber assessment. METHODS: A total of 21 ATTR patients, 20 healthy controls, and 18 asymptomatic carriers underwent a sensory conduction study from the right sural and non-dominant ulnar nerves. A motor conduction study from the right deep peroneal and non-dominant ulnar nerves, with their F waves, CSPs, and MnSPs, was performed. RESULTS: The amplitudes of the sural and ulnar sensory nerves and of the peroneal and ulnar motor nerves were reduced in ATTR patients compared to the other groups. F waves from the ulnar and peroneal nerves showed no differences between the three groups. The CSP and MnSP latency, but not amplitude, were increased in both the ulnar and peroneal nerves of ATTR patients. CONCLUSIONS: ATTR patients showed axonal involvement of large sensory and motor nerve fibers and demyelinating features of small sensory fibers.

Autonomic and neuropathic complaints of long-COVID objectified: an investigation from electrophysiological perspective.

PURPOSE: Here , we aimed to assess the frequency and phenomenology of autonomic and neuropathic complaints of long-COVID and to evaluate them by means of electrophysiology. METHODS: Step 1. Patients with prior COVID-19 infection were screened by COMPASS-31 and mTORONTO to create the target population for further evaluation. Step 2. Patients with high scores were invited for a detailed history of their complaints and electrophysiological analysis, which included nerve conduction studies, cutaneous silent period (CSP), and sympathetic skin response (SSR). We also constituted a control group composed of healthy subjects of similar age and sex for electrophysiological analysis. RESULTS: There were 106 patients, who matched the study criteria. Among them, thirty-eight patients (%35.8) had neuropathic or autonomic complaints or both. Fatigue and headache were significantly more frequent in patients with autonomic and neuropathic complaints. Detailed examination and electrophysiological evaluation were performed in 14 of 38 patients. Neuropathic complaints were patchy and proximally located in the majority. The entire CSP suppression index was higher in the patients (p = 0.002). There was no difference in palmar and plantar SSR between patients and healthy subjects. mTORONTO scores were negatively correlated with palmar and plantar SSR amplitudes, and the correlation was moderate. CONCLUSION: Neuropathic or autonomic complaints were seen in more than one-third of patients with long-COVID. Neuropathic complaints were generally patchy, proximally predominant, asymmetric, or diffuse. The CSP suppression index was abnormal whereas SSRs were normal.

Modulation of Motor Evoked Potentials via the Cutaneous Silent Period within Proximal-Distal Muscles in the Upper-Limb.

A single pulse of high intensity electrical current delivered to the digits of the hand during voluntary contractions produces a period of decreased electromyographic (EMG) activity, known as a cutaneous silent period (CSP) (Caccia and Violini, 1973; Inghilleri et al., 1997; Uncini et al., 1991). Pairing transcranial magnetic stimulation (TMS) with digit stimulation results in motor evoked potentials (MEPs) with reduced amplitudes in a thenar muscle (Kofler, 2008). It is not known if similar behavior can be observed in more proximal upper-limb muscles. The current study investigated the CSP on several muscles throughout the upper-limb. Fourteen subjects performed isometric contractions with the following muscles: abductor pollicis brevis (APB), flexor carpi radialis (FCR), extensor carpi radialis (ECR), biceps brachii (BIC), triceps brachii (TRI), anterior deltoid (AD), and posterior deltoid (PD). During the isometric contractions, subjects experienced three different stimulation conditions: electrical stimulation (10x perceptual threshold) of digit II only (CSP), transcranial magnetic stimulation only (TMS), and a pairing of digit II stimulation and TMS (TMS+). The TMS evoked MEP was significantly greater than the TMS+ MEP for APB (p < 0.001), FCR (p = 0.006), and BIC (p < 0.049) muscles. The opposite relationship was seen within the PD (p < 0.047) muscle. An ANOVA test of normalized MEP values (TMS+/TMS) showed significant differences in APB vs TRI (p = 0.004) and PD (p = 0.003), and in FCR vs TRI (p = 0.046) and PD (p = 0.037) muscles. The results suggest that the CSP modulates descending drive differentially across upper-limb muscles.

Alteration of cortical but not spinal inhibitory circuits in idiopathic scoliosis.

Background: The pathogenesis of adolescent idiopathic scoliosis (AIS), including the role of brain and spinal inhibitory circuits, is still poorly elucidated. The aim of this study was to identify which central inhibitory mechanisms are involved in the pathogenesis of AIS.Design: A prospective neurophysiological study, using a battery of neurophysiological tests, such as cutaneous (CuSP) and cortical (CoSP) silent periods, motor evoked potentials (MEP) and paired-pulse transcranial magnetic stimulation (ppTMS).Settings: Neurophysiological laboratory.Participants: Sixteen patients with AIS (14 females, median age 14.4) and healthy controls.Outcome measures: MEPs were obtained after transcranial magnetic stimulation (TMS) and recorded from the abductor pollicis muscle (APB). ppTMS was obtained at interval ratios (ISI) of 1, 2, 3, 6, 10, 15 and 20 ms. The cortical silent period (CoSP) was recorded from the APB. The cutaneous silent period (CuSP) was measured after painful stimuli delivered to the thumb while the subjects maintained voluntary contraction of the intrinsic hand muscles. The data were analyzed and compared with those from healthy subjects.Results: The CoSP duration was significantly prolonged in AIS patients. A significantly higher amplitude of ppTMS for ISI was found in all AIS patients, without remarkable left-right side differences. No significant difference in MEP latency or amplitude nor in the CuSP duration was obtained.Conclusion: Our observation demonstrates evidence of central nervous system involvement in adolescent idiopathic scoliosis (AIS). Lower intracortical inhibition, higher motor cortex excitability, and preserved spinal inhibitory circuits are the main findings of this study. A possible explanation of these changes could be attributed to impaired sensorimotor integration predominantly at the cortical level.

Effects of Medications and Subthalamic Nucleus-Deep Brain Stimulation on the Cutaneous Silent Period in Patients With Parkinson's Disease.

OBJECTIVES: We sought to evaluate whether the cutaneous silent period (CSP) could be an electrophysiological indicator reflective of the effects of therapy for Parkinson's disease (PD), including anti-PD medications or deep brain stimulation (DBS). MATERIAL AND METHODS: We recorded the CSP in 43 patients with PD prior to and following the administration of medication during a pre-DBS evaluation (30 cases) and the "on" and "off" states of subthalamic nucleus DBS (13 cases). The CSP was elicited from the abductor pollicis brevis muscle by an electrical stimulation of the index finger that was 2, 4, and 15 times stronger than the sensory threshold (ST). We measured changes in latencies, including the onset, duration, and end of CSP, and waveform scores from 0 to 3. The correlation between the CSP score and unified PD rating score part III (UPDRS-III) also was assessed. RESULTS: The onset latency and duration of CSP were significantly different between high- (15ST) and low-strength stimulations (2ST and 4ST). However, there were no significant latency changes (onset, duration, end of CSP) before and after receiving medication, or during the on and off state of the DBS. Anti-PD medications substantially increased the CSP waveform score only in the 4ST state. However, the waveform score significantly increased in all stimuli states during the DBS-on state. Both medication and the DBS-on state decreased the UPDRS-III. Nevertheless, there was no statistically significant correlation between the UPDRS-III and CSP waveform scores. CONCLUSION: Different onset latencies and the duration of CSP between low- and high-strength stimuli support the hypotheses proposing two different reflex pathways. Despite being independent from the UPDRS-III, the CSP may be an electrophysiological indicator reflective of the changes in inhibitory activity to the spinal α-motoneuron in response to anti-PD medications and DBS.

Cutaneous silent period in ulnar neuropathy at the elbow.

INTRODUCTION/AIMS: The cutaneous silent period (CSP) reflects the function of A-delta sensory fibers. There are few studies on CSP in nerve entrapment syndromes. This study aims to evaluate the neurophysiological abnormalities of small-diameter sensory fibers in ulnar neuropathy at the elbow (UNE) by means of CSP. METHODS: We consecutively evaluated UNE patients at one electrodiagnostic laboratory. The CSP was obtained upon stimulating the fifth (D5) and third digits, recording from the first dorsal interosseous (FDI) and abductor pollicis brevis (APB) muscles. RESULTS: We enrolled 37 UNE patients (mean age 55.4 ± 11.2 y) and 30 controls (mean age 51.2 ± 11.1 y). The combinations of the D5-APB and D5-FDI mean onset latencies of CSP were significantly more prolonged in patients (83.7 ± 6.8 and 84.5 ± 8 ms, respectively) than in controls (78.2 ± 8.1 and 79.4 ± 7.6 ms, respectively). The D5-FDI duration of CSP was shorter in patients (52.2 ± 8.3 ms) than in controls (55.8 ± 7 ms). The mean of the onset latencies of D5-FDI and D5-APB was related to the clinical severity (P = .013 and .0025, respectively). D5-APB and D5-FDI onset latencies were more prolonged and the duration was shorter in the UNE group with absent ulnar sensory nerve action potentials (SNAPs) and axonal motor damage than in patients with preserved SNAPs and with demyelinating damage. DISCUSSION: CSP was able to demonstrate abnormalities of small-diameter myelinated sensory fibers. This damage was directly related to UNE severity and to axonal damage of motor fibers. Absence of a sensory large-diameter fiber response did not exclude preserved residual small fiber conduction.

Metabolic syndrome and anthropometric indices in CTS hands: an electrophysiological study.

INTRODUCTION: This study aims to evaluate the effect of metabolic syndrome (MetS) and anthropometric indices on carpal tunnel syndrome (CTS). METHODS: Forty-three healthy controls and 41 CTS patients were enrolled. Complaints of patients were assessed by Boston Questionnaire (BQ). MetS components were investigated. Wrist circumference, wrist depth, wrist width, palm width, and palm length were measured. Routine nerve conduction studies of median and ulnar nerves as well as the "sensitive" comparison tests were performed. Cutaneous silent period (CuSP) was studied by stimulating both second and fifth digital nerves while recording over thenar muscles. RESULTS: The vast majority of the participants were female and right-handed. CTS was bilateral in 61% of patients. Data of 109 hands were analyzed. MetS was more frequent in CTS patients. BQ scores were not related to MetS. Waist circumference, serum TG, and fasting glucose levels were higher in CTS patients. CTS hands with MetS had lower median CMAP amplitudes and increased sensory thresholds. Sensory thresholds were increased with both median and ulnar nerve stimulations suggesting a wider spread of peripheral nerve excitability changes in MetS presence. CuSPs were recorded from all 109 hands. CuSP latencies and durations were similar between controls and CTS patients. Wrist ratio was the only anthropometric index that was a statistically significant predictor for CTS development. CONCLUSION: MetS was more prevalent in CTS patients. Some clinical and electrophysiological features (mainly sensory thresholds) may worsen in presence of MetS, but not the wrist ratio.

Electrophysiological findings in patients with restless legs syndrome.

BACKGROUND: Restless legs syndrome (RLS) manifests as an urge to move the body to relieve the discomfortable sensations, primarily when resting, sitting, laying down, or sleeping. Diagnosis of RLS relies on clinical criteria, and the immobilization test was the only instrumental tool with equivocal results. OBJECTIVES: To assess different electrophysiological findings in patients with RLS, and compare the diagnostic values of these parameters in the diagnosis of RLS. METHODS: 30 patients with primary RLS and 30 controls who were matched for age and gender were studied. Participant's demographics, laboratory findings, and electrophysiological test, namely nerve conduction studies (NCS), cutaneous silent period (CSP), H reflex and sympathetic skin response (SSR), F-wave latency, amplitude, F-wave duration (FWD), and the ratio between FWD and duration of the corresponding compound muscle action potential (FWD/CMAPD) were analyzed. RESULTS: None of the patients showed altered NCS data. FWD of upper (12.37 ± 2.77 ms) and lower limb (21.71 ± 5.24 ms) were significantly longer in patients. Also, FWD/CMAP duration of the upper (1.03 ± 0.2) and lower limb (2.02 ± 0.55) was longer in patients. Likewise, they exhibited delayed CSP latency from TA (110.62 ± 13.73 ms) and APB (77.35 ± 12.16 ms) whereas the CSP duration from TA and APB was decreased (37.36 ± 11.59 ms; 42.55 ± 7.97 ms, respectively). The SSR latency was not different, and right-sided H reflex amplitude (5.07 ± 3.98 mV) and H/M ratio (0.65 ± 1.81) were significantly increased in the patient group. CONCLUSION: The data suggest that there may be a dysfunction of the inhibitory/excitatory circuits at a spinal level; and no pathology in the peripheral nerves. The unilateral difference of H reflex amplitude and H/M ratio may suggest asymmetrical central inhibitory dysfunction. Further prospective studies with larger cohorts are now needed to evaluate the pathophysiology of RLS with different neurophysiological assessment tools.

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.

The cutaneous silent period in motor neuron disease.

OBJECTIVE: To investigate the cutaneous silent period (CSP) by measuring its onset latency, duration and amount signal suppression in patients with motor neuron disease (MND) grouped according to the intensity of upper motor neuron involvement (UMN), and to test the effect of contralateral hand contraction. METHODS: Painful stimulation was applied at the V finger, and contraction recorded from the abductor digiti minimi (ADM) muscle (baseline condition). Afterwards, CSP was studied during strong contralateral ADM contraction (test condition). 10-15 consecutive traces were recorded for each condition, signals were rectified, averaged, and analyzed offline. RESULTS: 46 patients were investigated, 15 with progressive muscular atrophy (PMA), 16 with typical amyotrophic lateral sclerosis (ALS), 15 with primary lateral sclerosis/predominant UMN-ALS (PLS+UMN-ALS), and 28 controls. In the baseline condition, all MND groups showed delayed onset latencies (p = 0.001). There was no significant difference in the CSP duration. Suppression was lower in the PLS + UMN-ALS group (p = 0.004). In the control group, contralateral contraction did not change CSP, but onset latency shortened significantly in the PMA group. CONCLUSIONS: CSP onset latency is delayed in all investigated groups of MND, including in PMA, indicating subclinical UMN involvement. Changes in CSP can indicate UMN lesion in MND. SIGNIFICANCE: CSP should be explored to identify UMN involvement in MND.

Modulation of the excitatory phase following the cutaneous silent period by vibration.

INTRODUCTION: The post-inhibition excitatory phase (E3) of the cutaneous silent period (CSP) is attributed to the resynchronization of motoneuron activity following the inhibitory period but there is also evidence that a somatosensory startle reflex may contribute to this phase. We hypothesized that the startle reflex component contained in E3 will decrease during vibration. METHODS: Sixteen healthy individuals were included in the study. CSP was recorded from slightly contracted right thenar muscles after painful index finger stimulation, before, during, and immediately after vibration. The values of the percentage change of E3 relative to pre-stimulus baseline (E3%) were compared before, during, and after vibration for each individual. RESULTS: There was a reduction in E3% during vibration and the values returned to normal immediately after vibration (153.1 ± 43.5%, 115.2 ± 30.2%, 154.9 ± 68.2%, respectively; p = 0.030). DISCUSSION: E3 is reduced during vibration in healthy individuals, presumably due to suppression of a reflex component, which is superimposed upon the known resynchronization of motoneurons.

Cutaneous silent period in patients with spinal muscular atrophy type 2 and type 3.

OBJECTIVE: The aim of this study was to examine cutaneous silent periods (CSPs) in spinal muscular atrophy (SMA) type 2 and type 3 patients. METHODS: Fourteen patients with SMA and 14 healthy subjects were included. CSPs were recorded from thenar muscles after painful stimulation of the index finger during slight thumb abduction. CSP parameters (including onset latency, duration, index of suppression, long-loop reflex, and post-inhibitory rebound activity) were measured. All parameters were compared between SMA patients and healthy subjects using the Mann-Whitney U test. We then correlated CSP parameters to Hammersmith Functional Motor Scale Expanded (HFMSE) scores in SMA patients by Spearman-rho testing. RESULTS: No CSP parameter except E3% (i.e., the post-inhibitory rebound activity relative to pre-stimulus baseline) differed significantly between SMA patients and healthy subjects. E3% was significantly smaller in patients than healthy individuals. HFMSE scores of SMA patients correlated negatively with CSP duration and positively with E3%. DISCUSSION: Smaller E3%, correlating with longer CSP duration, in SMA patients with more severe clinical findings and therefore more marked motoneuron loss suggests that the E3 component following the CSP is directly affected by motoneuron loss.

Cannabinoids in multiple sclerosis: A neurophysiological analysis.

OBJECTIVES: To investigate the action of cannabinoids on spasticity and pain in secondary progressive multiple sclerosis, by means of neurophysiological indexes. MATERIAL AND METHODS: We assessed 15 patients with progressive MS (11 females) using clinical scales for spasticity and pain, as well as neurophysiological variables (H/M ratio, cutaneous silent period or CSP). Testing occurred before (T0) and during (T1) a standard treatment with an oral spray containing delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Neurophysiological measures at T0 were compared with those of 14 healthy controls of similar age and sex (HC). We then compared the patient results at the two time points (T1 vs T0). RESULTS: At T0, neurophysiological variables did not differ significantly between patients and controls. At T1, spasticity and pain scores improved, as detected by the Modified Ashworth Scale or MAS (P = .001), 9-Hole Peg Test or 9HPT (P = .018), numeric rating scale for spasticity or NRS (P = .001), and visual analogue scale for pain or VAS (P = .005). At the same time, the CSP was significantly prolonged (P = .001). CONCLUSIONS: The THC-CBD spray improved spasticity and pain in secondary progressive MS patients. The spray prolonged CSP duration, which appears a promising tool for assessing and monitoring the analgesic effects of THC-CBD in MS.

Small fiber neuropathy and related factors in patients with systemic lupus erythematosus; the results of cutaneous silent period and skin biopsy.

INTRODUCTION: Evaluating small nerve fibers in patients with systemic lupus erythematosus (SLE) using cutaneous silent period (CSP) and skin biopsy and assesssing the relationship between clinical signs, autoantibodies and neuropathic pain score. OBJECTIVE - METHODS: Fifty one SLE patients and 46 healthy volunteers were included in this study. Nerve conduction studies and CSP were performed both on upper and lower limbs in subjects. Skin biopsy was performed and the number of epidermal nerve density and IL-6 staining were evaluated. RESULTS: In SLE patients, CSP latencies were significantly prolonged both in lower and upper limbs and lower and upper extremity CSP durations were significantly shorter when compared to controls (p < 0.001). The number of epidermal nerve was significantly lower in SLE patients when compared to healthy controls (p < 0.001). CONCLUSION: We detected marked small nerve fiber damage in both lower and upper limbs in SLE patients using CSP. Decreased epidermal nerve density also supports this finding.

The effect of vitamin D replacement on spinal inhibitory pathways in women with chronic widespread pain.

Vitamin D replacement helps in pain reduction in patients with chronic widespread pain (CWP). But the current literature lack studies that investigate its mechanism. Cutaneous silent period (CSP) is the electrophysiologic analog of the spinal inhibitory pathways and an objective method to document their involvement. This study aims to show if vitamin D replacement has an effect on the spinal inhibitory pathways through CSP parameters. Female patients who have CWP with vitamin D deficiency were included. Patients received an 8-week replacement therapy of vitamin D. Patients' pain were evaluated using the visual analog scale (VAS) and Leeds assessment of neuropathic symptoms and signs pain scale (LANSS). Quality of life with Nottingham Health Profile (NHP) and CSP parameters were also recorded before and after treatment. A total of 51 patients were included in the final analyses. The mean age of the patients was 44.3 ± 12.7 (minimum 18-maximum 65). Mean symptom duration was 13.1 ± 6.7 (minimum3-maximum 24) months. Patients' mean BMI was 21.6 ± 3.9 (minimum 18.0 maximum 29.1). Patients' median VAS and LANSS scores decreased significantly (p < 0.01) and NHP scores improved significantly in all subsets (p < 0.01). Vitamin D replacement did not significantly change CSP latency and duration (p = 0.06 and p = 0.12).Vitamin D replacement does not seem to work via modifying the spinal inhibitory pathways that are involved in the formation of the cutaneous silent period. This is the first study to objectively investigate the effect of vitamin D replacement on central sensitization mechanisms.