Electrodiagnostic methods to verify Guillain-Barré syndrome subtypes in Istanbul: A prospective multicenter study.

BACKGROUND AND AIMS: This study aimed to identify the clinical characteristics and electrodiagnostic subtypes of Guillain-Barré syndrome (GBS) in Istanbul. METHODS: Patients with GBS were prospectively recruited between April 2019 and March 2022 and two electrodiagnostic examinations were performed on each patient. The criteria of Ho et al., Hadden et al., Rajabally et al., and Uncini et al. were compared for the differentiation of demyelinating and axonal subtypes, and their relations with anti-ganglioside antibodies were analyzed. RESULTS: One hundred seventy-seven patients were included, 69 before the coronavirus disease 2019 pandemic (April 2019-February 2020) and 108 during the pandemic (March 2020-March 2022), without substantial changes in monthly frequencies. As compared with the criteria of Uncini et al., demyelinating GBS subtype diagnosis was more frequent according to the Ho et al. and Hadden et al. criteria (95/162, 58.6% vs. 110/174, 63.2% and 121/174, 69.5%, respectively), and less frequent according to Rajabally et al.'s criteria (76/174, 43.7%). Fourteen patients' diagnoses made using Rajabally et al.'s criteria were shifted to the other subtype with the second electrodiagnostic examination. Of the 106 analyzed patients, 22 had immunoglobulin G anti-ganglioside antibodies (14 with the axonal subtype). They had less frequent sensory symptoms (54.5% vs. 83.1%, p = 0.009), a more frequent history of previous gastroenteritis (54.5% vs. 22.9%, p = 0.007), and a more severe disease as compared with those without antibodies. INTERPRETATION: Serial electrodiagnostic examinations are more helpful for accurate subtype diagnosis of GBS because of the dynamic pathophysiology of the disease. We observed no significant increase in GBS frequency during the pandemic in this metropolis.

Changes in blink reflex after simultaneous supraorbital and mental nerve stimulations in healthy subjects.

Background/aim: In this study, we investigated the blink reflex (BR) after simultaneous and asynchronous stimulation of two trigeminal nerve branches. The objective was to characterize the physiology of trigeminal and facial circuits. Materials and methods: We performed three sets of experiments: recording BR response i. after supraorbital nerve stimulation (SON), after mental nerve stimulation (MN), and after simultaneous SON and MN stimulation (SON+MN) in 18 healthy individuals; ii. after MN (at an intensity eliciting BR response) preceding SON at various interstimulus intervals (ISIs) in seven healthy subjects; iii after MN (at sensory threshold) preceding SON at various ISIs. We compared the magnitudes of early and late responses. Results: The R1 amplitude after simultaneous SON+MN stimulation was greater than responses after single stimulation of the same branches. After simultaneous stimulations, the R2 and R2c areas under the curve (AUC) were smaller than the arithmetic sums of R2 and R2c AUC obtained after single stimulations. The second experiment provided a recovery excitability curve. In the third step, we obtained facilitation of R1 and inhibition of late responses. Conclusion: The SON+MN stimulation caused an increased R1 circuit excitability compared to the arithmetic sum of the single stimulations; however, magnitudes of late responses did not potentiate. Thus, we have provided evidence for R1 circuit enhancement by simultaneous stimulation in humans, whereas modulation of late responses exhibited a recovery curve similar to that shown for paired SON stimulation.

Segmental Reflex, Long Latency Reflex, and Mixed Nerve Silent Period in Dystonia.

We hypothesized that "long latency reflexes" (LLRs), associated segmental reflex (SR), and mixed nerve silent periods (MnSPs) recorded on the distal upper extremity muscles would behave differently in patients with cervical dystonia and focal hand dystonia. We enrolled patients with cervical dystonia, generalized dystonia, focal hand dystonia, and healthy individuals. We recorded SR, LLRs, and MnSPs. The mean amplitude of SR on the affected side of focal hand dystonia was significantly lower (p = 0.010). The parameters related to LLRs and MnSPs were not different between groups. We suggest, using SR, LLRs, and MnSPs, we could not show an electrophysiological signature specific to dystonia.

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).

ADCY5 gene mutation: a case report.

BACKGROUND: ADCY5 mutation is a clinical condition that has been described in limited numbers in the literature, causing hyperkinetic movement disorder, and may be sporadic or familial. PATIENT DESCRIPTION: This report looks at the involuntary movements that started early in life in a 5-year-old girl. RESULTS: Patient's electroensephalogram and cranial magnetic resonance imaging were normal. Metabolic scans were normal. ADCY5 mutation was found in whole exome sequencing of the patient who did not have a similar family history. CONCLUSION: Some features such as the worsening of involuntary movements after sleep and the presence of hypotonia in our patient suggested this mutation. Our patient is resistant to more than one drug. With this report, we aimed to pave the way for better understanding of the gene and the discovery of different treatment options.

Postural tremor in L-2-hydroxyglutaric aciduria is associated with cerebellar atrophy.

OBJECTIVE: In this study, we performed analysis of brainstem reflexes and movement disorders using surface polymyogram in L-2-hydroxyglutaric aciduria (L2HGA). We also reviewed all cases in the literature with detailed clinical and radiological description to analyze the anatomical correlates of involuntary movements. PATIENTS AND METHOD: We performed surface electromyography of appropriate muscles, long-loop reflexes, and somatosensory evoked potentials and analyzed the neuroimaging findings in patients with L2HGA and recorded blink reflex (BR), auditory startle response (ASR), and startle response after somatosensory stimuli (SSS) in patients and healthy subjects. We also performed a systematic literature search to identify the association of neuroimaging findings and movements disorders in previous patients with L2HGA. RESULTS: Thirteen patients were enrolled in the study. Among them, ten had low-amplitude postural tremor with a frequency between 4 and 7 Hz. The tremor was predominant on distal parts of the upper extremities. Postural tremor was accompanied by negative myoclonus in one-third. The BR, ASR, and SSS, all, were hypoactive. There was a close association of postural tremor with cerebellar atrophy in patients who participated in this study and by the analysis of the previously reported patients. CONCLUSIONS: Low-amplitude postural tremor is common in L2HGA. It is related with cerebellar atrophy. Although the neuroimaging shows no overt lesions at the brainstem, there is a functional inhibition at this level.

Long latency trigemino-cervical reflex in restless legs syndrome.

OBJECTIVE: The trigemino-cervical complex (TCC) seems under dopaminergic inhibitory control and the abnormalities of trigemino-cervical reflex (TCR) have been reported in disorders associated with the dopaminergic system and various pain disorders. If the inhibitory response in TCC is likely dopaminergic, we hypothesized that TCR, which has never been evaluated in restless legs syndrome (RLS) patients before, would be also abnormal. METHODS: TCR was recorded from bilateral sternocleidomastoid and splenius capitis muscles in consecutive 15 drug-naive RLS patients and 16 age- and sex-matched healthy subjects. The right and left infraorbital branches of the trigeminal nerve were stimulated by percutaneous electrical stimulation separately. The presence rates, onset latencies, amplitudes, and durations of responses were measured and compared between patients with RLS and controls. RESULTS: The presence rates, onset latencies and amplitudes of TCR responses were similar between RLS patients and controls, however, the durations of responses were bilaterally longer in RLS patients compared to healthy volunteers. CONCLUSIONS: Hyperexcitability of TCR suggests defective sensory processing in the brainstem probably due to impairment of descending inhibitory dopaminergic system in RLS. The sensitization of TCC in RLS patients may also be a possible factor that might explain the association of RLS and pain disorders.

[Comparison of long-latency reflex and mixed nerve silent period responses in various hypokinetic movement disorders]. / A hosszú latenciájú reflexválaszoknak és a kevert idegek csendes periódusainak összehasonlítása különbözo hipokinetikus mozgási rendellenességekben.

Background and purpose: Long-latency reflex and mixed nerve silent period responses are electrophysiological methods to study the sensorimotor functions of the central nervous system. Here we aimed to study long-latency reflexes and mixed nerve silent period responses in different types of hypokinetic movement disorders in order to find an electrophysiological landmark to distinguish them. Methods: We included 39 patients with idiopathic Parkinson's disease (IPD), 12 patients with multiple system atrophy (MSA), 10 patients with corticobasal syndrome (CBS), 5 patients with progressive supranuclear palsy (PSP) and 26 healthy participants. We recorded the segmental reflex, the long-latency reflexes and the mixed nerve silent period responses for each participant. Results: C reflex, long-latency reflex-I and long-latency reflex-III responses were not obtained in any patients with PSP. Long-latency reflex amplitude/ F amplitude ratio was significantly lower in patients with IPD and PSP compared to healthy individuals (p=0.036, p=0.006 respectively). The mixed nerve silent period end latencies were significantly longer in IPD, MSA, CBS groups compared to the healthy individuals (p=0.026, p=0.050, p=0.008 respectively). Conclusion: We suggest that recording long-latency reflex, particularly C reflex responses may provide promising results in distinction of CBS and MSA from PSP. Prospective studies with clinical findings and brainstem reflexes may offer more information.

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.

Electrophysiological investigation for autonomic dysfunction in patients with myasthenia gravis: A prospective study.

BACKGROUND AND PURPOSE: Myasthenia gravis (MG) is an autoimmune disorder of neuromuscular transmission. Autonomic dysfunction is not a commonly known association with MG. We conducted this study to evaluate autonomic functions in MG & subgroups and to investigate the effects of acetylcholinesterase inhibitors. METHODS: This study comprised 30 autoimmune MG patients and 30 healthy volunteers. Autonomic tests including sympathetic skin response (SSR) and R-R interval variation analysis (RRIV) was carried out. The tests were performed two times for patients who were under acetylcholinesterase inhibitors during the current assessment. RESULTS: The RRIV rise during hyperventilation was better (p=0.006) and Valsalva ratio (p=0.039) was lower in control group. The SSR amplitudes were lower thereafter drug intake (p=0.030). As much as time went by after drug administration prolonged SSR latencies were obtained (p=0.043).Valsalva ratio was lower in the AchR antibody negative group (p=0.033). CONCLUSION: The findings showed that both ocular/generalized MG patients have a subclinical parasympathetic abnormality prominent in the AchR antibody negative group and pyridostigmine has a peripheral sympathetic cholinergic noncumulative effect.

Modulation of the Somatosensory Blink Reflex in the Peripersonal Space Is Defective in Episodic Migraine.

OBJECTIVE: In migraine, there is an altered behavior of patients during the attack and an altered connectivity in the cortical structures modulating and encoding the sensation and pain. Thus, we hypothesized that the extent of the peripersonal space (PPS) and the responses in the PPS may change during a migraine attack. For this reason, we analyzed the modulation of somatosensory blink reflex (SBR) in the PPS during episodic migraine. DESIGN: Cross-sectional assessment of modulation of SBR in patients with migraine. SETTING: Headache outpatient clinic of a tertiary referral center. SUBJECTS: We included 22 patients with episodic migraine, of whom 13 individuals were in the interictal period and nine were experiencing a headache episode. We also included 14 healthy individuals. The three groups were similar in age and gender. METHODS: SBR was recorded when the participants were sitting with their forearm in the extrapersonal space and also when their hands were in the PPS surrounding the face. Latency, amplitude, and area under the curve (AUC) were measured and compared. RESULTS: The amplitude and AUC of the SBR were significantly higher in patients during the attack compared with healthy subjects. The magnitude of the SBR was increased in the PPS in healthy subjects, whereas the increase was not significant in patients during the attack or in the interictal period. CONCLUSIONS: We think that the modulation in the PPS is defective in patients with migraine both during the acute attack and in the interictal phase, suggesting diminished top-down modulation of the SBR.

Late component of trigemino-cervical reflex: changes according to age and gender.

BACKGROUND: Trigemino-cervical reflex (TCR) is a protective reflex which is elicited by the stimulation of any branch of the trigeminal nerve. After infraorbital stimulation, an early and late components have been described. The aim of this study was to find out whether there are age- or gender-related changes in the long-latency (RII) component of TCR. METHOD: We included consecutive 53 healthy subjects (20 men, 37.7%) who had normal neurological examination. The mean age was 45.1 ± 14.3 years (age range 18-75 years). TCR was recorded simultaneously from bilateral sternocleidomastoid (SCM) and splenius capitis (SC) muscles with surface electrodes after stimulating right or left infraorbital branch of the trigeminal nerve, separately. We compared latency, amplitude, and duration according to gender and age. RESULTS: The amplitudes of SC responses were significantly higher in women compared to men. The duration of SCM response was significantly longer in subjects above the age of 50 years compared to younger patients. The latency of the SC response was significantly delayed above the age of 40 years. CONCLUSION: There are age- and gender-related changes in TCRs probably due to changes in the motoneurons of the SC and SCM muscles.

Effects of vibration on cutaneous silent period.

Suppression of an ongoing muscle contraction following noxious digital stimulation is called cutaneous silent period (CSP) which is under the influence of several physiological factors. In this study, we aimed to evaluate the influence of group Ia afferents on the cutaneous silent period (CSP) by applying 2-min vibration. CSP was obtained from abductor pollicis brevis muscle after stimulating index finger. The recordings were repeated three times-before, during and after vibration-which was applied over the tendon of flexor carpi radialis muscle. Onset latency, duration and magnitude of total CSP, inhibitory phases I1 and I2, and of the long-loop reflex were measured and compared. Suppression indices of CSP, I1 and I2 increased significantly during and after vibration, indicating significantly less exteroceptive EMG suppression outlasting the time of vibration. Vibration also caused mild shortening of I2 end latency (p = 0.048) and I2 duration (p = 0.019). Our findings indicate that vibration exerts a powerful influence on CSPs and causes reduction in the magnitude of exteroceptive EMG suppression during and after vibration. Although vibration is known to activate Ia afferents, we cannot exclude contribution of other afferents, e.g. mechanoreceptors, as well as pre- or postsynaptic inhibitory effects on ensuing interneurons, or enhanced vibration-related excitatory influence.

Recovery function of somatosensory evoked potentials in juvenile myoclonic epilepsy.

Objective: We analysed the recovery function of somatosensory evoked potentials (SEPs) in juvenile myoclonic epilepsy (JME) patients. We hypothesized that there may be disinhibition in the recovery of SEPs at 20-100 ms intervals in JME patients. Methods: We recorded SEPs and SEP recovery in 19 consecutive patients with JME admitted for a routine follow-up examination, and in a control group composed of 13 healthy subjects who were similar to the patient group regarding age and sex. The recovery function of SEPs was examined using paired stimuli at 30, 40, 60, and 100 ms intervals. Results: The amplitudes of N20-P25 and P25-N33 components were higher in patients with JME. Ten patients had high-amplitude SEPs. By paired stimulation, there was inhibition of SEPs in both groups. The mean recovery percentages of N20-P25 and P25-N33 components at 30, 40, 60, and 100 ms were not different between healthy subjects and patients with JME. Conclusions: The recovery function of SEP is normal in JME even in the presence of high-amplitude SEPs.

Fear leads to a deficit of prepulse inhibition of blink reflex in healthy humans.

OBJECTIVE: We aimed to analyze whether or not fear conditioning exerts an effect on prepulse inhibition (PPI) of blink reflex (BR). To create fear conditioning, we used fearful faces. Since fearful faces lead to a specific set of fear conditioning, we hypothesized PPI of BR would change under the observation of fearful faces. METHOD: We included 17 healthy subjects with a mean age of 30.8 ± 6.9 years and seven healthy subjects with a mean age of 57.7 ± 7.3 years between January 2018 and June 2018 and recorded PPI of BR. The recordings were done before observation of any image, during observation of images, and immediately after observation of images. Observation of images included observation of fearful faces for 30 s and a neutral image of a white screen for 30 s (in a randomized order). RESULTS: There was a R2-PPI deficit during observation of fearful faces in each group whereas R2-PPI fully developed at other time points. R1 amplitude and R2 magnitude were lower during observation of any image compared with baseline and post-observation time points. CONCLUSION: In conclusion, a deficit of R2-PPI develops during observation of fearful faces in humans which is probably related to activation of the amygdala.

Prepulse modulation and recovery of trigemino-cervical reflex in normal subjects.

OBJECTIVE: In this study, we analyzed the inhibitory control on the trigemino-cervical reflex (TCR), and whether or not prepulse modulation (PPM) has an effect on TCR. Thus, we studied the PPM of TCR. We hypothesized that TCR would presumably be under the modulatory effect after the prepulse stimulus similar to blink reflex (BR). We also studied the recovery of TCR which was previously shown. METHODS: We included 13 healthy individuals. All subjects underwent recordings of TCR, TCR-PPM, and recovery of TCR. For TCR-PPM, a subthreshold stimulus to second finger 50 or 100 ms before the test stimulus was applied. For recovery of TCR, two stimuli at the infraorbital nerve were applied at 300, 500, and 800 ms interstimulus intervals (ISIs). RESULTS: There was an inhibition of bilateral late responses of TCR at the ISIs of both 50 ms and 100 ms. There was no change of latencies. Full recovery of TCR did not develop even at the ISI 800 ms. DISCUSSION: We have provided an evidence for the TCR-PPM in healthy subjects for the first time in this study. The prepulse inhibition is attributed to the functions of the pedunculopontine tegmental nucleus. Our study provides a strong indication that there are connections between pedunculopontine tegmental nucleus and trigemino-cervical circuit, which produces TCR.

Role of mesial temporal lobe structures in sensory processing in humans: a prepulse modulation study in temporal lobe epilepsy.

Prepulse modulation (PPM) is an electrophysiological method which enables to assess sensory processing in vivo. Reflex responses may be facilitated or inhibited (prepulse inhibition, PPI) after a weak stimulus. Theoretically, in animal studies, the generator of PPI involves pedunculopontine nucleus which is modulated by various structures, including amygdala. We aimed to investigate whether or not there was a role of limbic structures in the generation of PPM in humans. For this purpose, we studied PPM of the blink reflex (BR) in 10 patients with mesial temporal lobe epilepsy (MTLE group) and in nine patients who had previously undergone amygdala resection for medically resistant MTLE (surgery group). A control group including 19 healthy volunteers was formed. Blink reflex, BR-PPM and BR excitability recovery were recorded in all participants. Two components of BR, first early ipsilateral component (R1) and second late bilateral components (R2 and R2c) were identified. All BR parameters after single stimulation were normal in all groups. Compared to healthy subjects, R2-PPI was more pronounced in the surgery group whereas there was a R2-PPI deficit in the MTLE group. R2-PPI deficit in the MTLE group was more prominent on the lesion side. Ipsilesional R1 facilitation was more evident at ISI of 100 ms in both MTLE and surgery groups compared to healthy subjects. BR excitability recovery was not different between groups. MTLE in humans leads to a PPI deficit. Interestingly, removal of amygdala in humans with MTLE probably provides more efficient functioning of PPI network. Amygdala and hippocampus play roles in the human R2-PPI circuit. Modulation of R1 facilitation is unilateral whereas the modulation of R2-PPI is bilateral, though asymmetric.

Electrophysiological Investigations in Orthostatic Myoclonus: Preliminary Findings.

We report the clinical and electrophysiological findings in seven patients with orthostatic myoclonus (OM) associated with gait initiation failure and falls. OM is one of the causes of unsteadiness of stance and gait, and it may develop as a symptom of neurodegenerative disorders. Both positive myoclonic bursts and negative myoclonus may be seen in electrophysiological recordings, and electrophysiological analysis suggests a subcortical origin for OM.

Reorganization of sensory input at brainstem in hemifacial spasm and postparalytic facial syndrome.

We hypothesized the filtering of sensory input from face and hand at brainstem may reorganize in hemifacial spasm (HFS) and postparalytic facial syndrome (PFS). Thus, we examined the prepulse inhibition of blink reflex (BR-PPI) in HFS and PFS. We included 12 healthy subjects, 13 patients with HFS, and 11 patients with PFS. Baseline BR, BR recovery at interstimulus interval (ISI) of 300 ms and BR-PPI at ISI of 100 ms were performed on the right sides of healthy subjects and on both sides of patients. Within-subject analysis showed baseline BR and BR-PPI were similar between asymptomatic and symptomatic sides of patients with HFS whereas BR recovery was higher on the symptomatic side. In the PFS group, latency of R2 during baseline BR recording was longer (p = 0.022) and R2 amplitude (p = 0.046) was reduced on the symptomatic side compared to asymptomatic side. Reduction of R2 area in BR-PPI recordings was also the lowest in HFS compared to other two groups (p = 0.000); however, it was also lower in patients with PFS compared to healthy subjects (p = 0.018). BR-PPI was decreased on both sides of patients. The mean R2 recovery was higher on both sides of patients with HFS and PFS (p = 0.007). Filtering of facial sensory input is decreased probably to monitor and to correct the sequence of facial movements in these disorders.