Anti-GM2 antibody positive Guillain-Barré syndrome presenting with ataxia in a pediatric patient: An atypical manifestation.

Guillain-Barré syndrome (GBS) is the most prevalent cause of acquired paralytic neuropathy in children, however, ataxia as the initial presenting sign in children is very rare. Antiganglioside antibodies are presumed to have an important role in the pathophysiology and some phenotypic correlations have been reported. Anti-GM2 antibody, unlike other antibodies, is far less detected in GBS. Here, we report a 7.5-year-old female, initially presenting with ataxia, an atypical presenting symptom in a child, is promptly diagnosed and treated successfully as GBS. Atypical history of urinary infection in our patient is an interesting aspect. The presence of isolated anti-GM2 IgM antibody and ataxia in a pediatric patient is rare. In this case report, we aim to describe an atypical initial presentation, with positive anti-GM2 antibodies, as well as review literature on isolated anti-GM2 positive pediatric GBS patients.

The Complex Genetic Landscape of Hereditary Ataxias in Turkey and Implications in Clinical Practice.

BACKGROUND: The genetic and epidemiological features of hereditary ataxias have been reported in several populations; however, Turkey is still unexplored. Due to high consanguinity, recessive ataxias are more common in Turkey than in Western European populations. OBJECTIVE: To identify the prevalence and genetic structure of hereditary ataxias in the Turkish population. METHODS: Our cohort consisted of 1296 index cases and 324 affected family members. Polymerase chain reaction followed by Sanger sequencing or fragment analysis were performed to screen for the trinucleotide repeat expansions in families with a dominant inheritance pattern, as well as in sporadic cases. The expansion in the frataxin (FXN) gene was tested in all autosomal recessive cases and in sporadic cases with a compatible phenotype. Whole-exome sequencing was applied to 251 probands, selected based on the family history, age of onset, and phenotype. RESULTS: Mutations in known ataxia genes were identified in 30% of 1296 probands. Friedreich's ataxia was found to be the most common recessive ataxia in Turkey, followed by autosomal recessive spastic ataxia of Charlevoix-Saguenay. Spinocerebellar ataxia types 2 and 1 were the most common dominant ataxias. Whole-exome sequencing was performed in 251 probands with an approximate diagnostic yield of 50%. Forty-eight novel variants were found in a plethora of genes, suggesting a high heterogeneity. Variants of unknown significance were discussed in light of clinical data. CONCLUSION: With the large sample size recruited across the country, we consider that our results provide an accurate picture of the frequency of hereditary ataxias in Turkey. © 2021 International Parkinson and Movement Disorder Society.

Brainstem Reflexes in Systemic Lupus Erythematosus Patients Without Clinical Neurological Manifestations.

INTRODUCTION: We aimed to assess central and peripheral nervous system involvement in systemic lupus erythematosus (SLE) patients without any neurological signs and symptoms by performing electrophysiological investigations. METHODS: Thirty-eight SLE patients and 35 healthy volunteers participated in this study. Peripheral nerve conduction and brainstem reflexes were evaluated by performing nerve conduction studies (NCSs) and blink reflex (BR) and masseter inhibitory reflex (MIR) recordings. RESULTS: Eleven patients (29%) had an abnormality in at least 1 NCS parameter, and 1 (2.6%) patient was diagnosed with polyneuropathy. The number of patients with abnormal BR and MIR was 23 (60.5%) and 14 (37%), respectively. The contralateral R2 latency of BR and the silent period 1 (SP1) latency of MIR were significantly prolonged in the patients compared with the controls (p=0.015 and p<0.001, respectively). CONCLUSION: This study showed that irrespective of peripheral nervous system involvement, brainstem reflexes could be affected in SLE patients even without clinical neurological findings. Brainstem reflex abnormalities suggested that the functional integrity of the inhibitory or excitatory interneurons in the lateral caudal pons and lateral medulla is disturbed in SLE patients.

Motor-Unit Number Estimation Is Sensitive in Detecting Motor Nerve Involvement in Patients with Carpal Tunnel Syndrome.

BACKGROUND AND PURPOSE: We compared the motor-unit number estimation (MUNE) findings in patients who presented with signs and/or findings associated with carpal tunnel syndrome (CTS) and healthy controls, with the aim of determining if motor-unit loss occurs during the clinically silent period and if there is a correlation between clinical and MUNE findings in CTS patients. METHODS: The study investigated 60 hands of 35 patients with clinical CTS and 60 hands of 34 healthy controls. Routine median and ulnar nerve conduction studies and MUNE analysis according to the multipoint stimulation method were performed. RESULTS: The most common electrophysiological abnormality was reduced conduction velocity in the median sensory nerve (100% of the hands). The MUNE value was significantly lower for the patient group than for the control group (p=0.0001). ROC analysis showed that a MUNE value of 121 was the optimal cutoff for differentiating between patients and controls, with a sensitivity of 63.3% and a specificity of 68.3%. MUNE values were lower in patients with complaints of numbness, pain, and weakness in the median nerve territory (p<0.05, for all comparisons), and lower in patients with hypoesthesia than in patients with normal neurological findings (p=0.023). CONCLUSIONS: The MUNE technique is sensitive in detecting motor nerve involvement in CTS patients who present with sensorial findings, and it may be useful in detecting the loss of motor units during the early stages of CTS. Larger-scale prospective clinical trials assessing the effect of early intervention on the outcome of these patients would help in confirming the possible benefit of detecting subclinical motor-unit loss in CTS.

Blink reflex in migraine headache.

OBJECTIVE: Activation of trigeminovascular system is thought to play an important role in migraine pathogenesis. Blink reflex (BR) test is an easy method to study the trigeminal system. Latencies recorded in BR test were evaluated to examine neurophysiological changes that occur in migraine patients. METHODS: A total of 40 patients diagnosed with migraine (9 with aura and 31 without aura) according to the International Headache Society (IHS) International Classification of Headache Disorders, 2nd edition, and 30 healthy control subjects were assessed using BR test. Supraorbital nerve was stimulated on each side, and unilateral early component (R1), and bilateral late component (R2) latencies were evaluated. RESULTS: Significantly longer latency values were recorded on both right and left sides (RR1 and LR1) as well as both ipsilateral and contralateral R2 on the left side (LR2i and LR2c) in the migraine group compared to the control group. Longer RR1 and LR1 latencies were found in patients with migraine who had an attack at the time of study (p<0.01). There was no statistically significant correlation between the location of pain and latencies in the interictal period (p>0.05). But significantly longer R1 and R2i latencies were found at the symptomatic side of patients examined during the headache attack (p=0.037 and p=0.028 respectively). There was no statistically significant correlation between the recorded latencies and gender, attack duration, attack frequency and migraine type (p>0.05). CONCLUSION: Results of BR test in the present study are thought to point to a dysfunction in brainstem and trigeminovascular connections of patients with migraine headache and support the trigeminovascular theory of migraine.

Exome Sequence Analysis Suggests that Genetic Burden Contributes to Phenotypic Variability and Complex Neuropathy.

Charcot-Marie-Tooth (CMT) disease is a clinically and genetically heterogeneous distal symmetric polyneuropathy. Whole-exome sequencing (WES) of 40 individuals from 37 unrelated families with CMT-like peripheral neuropathy refractory to molecular diagnosis identified apparent causal mutations in ∼ 45% (17/37) of families. Three candidate disease genes are proposed, supported by a combination of genetic and in vivo studies. Aggregate analysis of mutation data revealed a significantly increased number of rare variants across 58 neuropathy-associated genes in subjects versus controls, confirmed in a second ethnically discrete neuropathy cohort, suggesting that mutation burden potentially contributes to phenotypic variability. Neuropathy genes shown to have highly penetrant Mendelizing variants (HPMVs) and implicated by burden in families were shown to interact genetically in a zebrafish assay exacerbating the phenotype established by the suppression of single genes. Our findings suggest that the combinatorial effect of rare variants contributes to disease burden and variable expressivity.

The reliability of medial and lateral plantar nerve recordings in healthy elderly individuals.

The aim of this study was to investigate the reliability of medial plantar (MP) and lateral plantar (LP) nerve conduction studies (NCS) in healthy individuals aged >65 years, and to obtain reference values for this age group. The study included 81 healthy subjects. MP response was absent in only 2 subjects, but LP response could not be obtained bilaterally in 43 of the 81 subjects. Regression analysis showed that MP NCS could be reliably performed in those aged ≤ 72 years and normal values for MP nerve in individuals aged 66-72 years would be strongly against a large-fiber neuropathy. However, LP response was absent in 53.1 % of the healthy elderly subjects; therefore, we think it is unreliable to study the LP nerve in this age group.

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.

Motor nerve impairment in diabetic patients with symmetrical distal sensory polyneuropathy: a single nerve fiber conduction velocity study.

INTRODUCTION: In this study we investigated the clinical utility of single fiber conduction velocity (SF-CV) testing in the evaluation of motor nerve function in diabetic patients with signs and symptoms of symmetrical distal sensory polyneuropathy (DSP). SF-CV findings were compared with conventional nerve conduction studies (NCS). METHODS: Twenty-eight consecutive type 2 diabetic patients with clinically diagnosed DSP were studied. RESULTS: SF-CV testing of the tibial nerve was abnormal in 16 (57.1%) patients. Twelve patients with normal conventional motor NCS had abnormal findings by tibial SF-CV. SF-CV testing of the tibial nerve was significantly superior to all other motor NCS. CONCLUSIONS: SF-CV testing of the tibial nerve often demonstrates motor nerve impairment in diabetic patients with sensory DSP when conventional NCS are normal.

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.

The Relationship between Quiescent Inflammatory Bowel Disease and Peripheral Polyneuropathy.

BACKGROUND/AIMS: Inflammatory bowel disease is a chronic, recurrent disorder that involves multiple organ systems. Polyneuropathy is the most common neurological manifestation. The aim of the present study was to investigate the relationship between polyneuropathy and inflammatory bowel disease. METHODS: The study included 40 patients with infl ammatory bowel disease (20 with ulcerative colitis and 20 with Crohn's disease) and 24 healthy controls. The patients had no clinical signs or symptoms of polyneuropathy. Nerve conduction studies were performed using an electroneuromyography apparatus. RESULTS: Mean distal motor latencies, conduction velocities, and F wave minimum latencies of the right median nerve were signifi cantly abnormal in the patient group, compared to the healthy controls (p<0.05). CONCLUSIONS: Some electrophysiological alterations were observed in chronic inflammatory bowel disease patients who showed no clinical signs. While investigating extra-intestinal manifestations in inflammatory bowel disease patients, nerve conduction studies must be performed to identify electrophysiological changes and subclinical peripheral polyneuropathy, which can subsequently develop.

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.

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.

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.

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.

Madras motor neuron disease in Turkey.

We present a 19-year-old female patient complaining of hoarseness and eyelid drooping. The neurological examination and laboratory investigations including genetic, radiological and electrophysiological evaluations were consistent with a juvenile-onset, predominantly bulbar, motor neuron disease with sensorineural hearing loss. The syndrome fulfilled the diagnostic criteria of Madras Motor Neuron Disease (MMND). Very few cases with MMND have been reported to date, and the majority are from south-eastern Asia. This is the first case reported from Turkey and indicates that the disease is not only regional but may also occur on the basis of rare de novo mutations.

The utility of lumbar paraspinal mapping in the diagnosis of lumbar spinal stenosis.

OBJECTIVE: The aim of this prospective, blinded and controlled study is to evaluate the utility of lumbar paraspinal mapping in the diagnosis of lumbar spinal stenosis. DESIGN: The subjects were assessed and allocated into three groups according to clinical and radiologic features with a standardized assessment protocol. These three groups were clinical and radiologic lumbar spinal stenosis, radiologic lumbar spinal stenosis, and the control group. The measurements of magnetic resonance imaging studies were performed by a blinded radiologist. An electromyographer who was masked to patients' data performed all the nerve conduction tests, lower-limb needle electromyography, and lumbar paraspinal mapping. The relations of clinical, radiologic, and electrophysiologic findings were investigated. RESULTS: Sixty-two patients were enrolled in the study. Two patients were eliminated because electrophysiologic studies showed polyneuropathy. There were 28, 16, and 16 patients in clinical and radiologic lumbar spinal stenosis, radiologic lumbar spinal stenosis, and control groups, respectively. In the clinical and radiologic lumbar spinal stenosis group, the findings of limb needle electromyography were inconsistent with 50% acute and 46.4% chronic radiculopathy. However, the paraspinal mapping showed that there were fibrillation potentials and positive sharp waves in at least two levels in 92.8% of the patients in clinical and radiologic lumbar spinal stenosis. The mean total paraspinal mapping score was 33.64 ± 21.17, which was significantly higher than the radiologic lumbar spinal stenosis and control groups. In the radiologic lumbar spinal stenosis group, the findings of paraspinal mapping were normal in 93.8% of the patients. Paraspinal mapping technique was found to be better correlated to the clinical findings than magnetic resonance imaging in asymptomatic patients. In the control group, 6 of 14 patients had high total paraspinal mapping scores (range, 0-9). Those patients with higher paraspinal mapping scores in the control group were mostly diagnosed with acute monoradiculopathy caused by disc herniation. CONCLUSIONS: Paraspinal mapping technique is a sensitive method in the diagnosis of lumbar spinal stenosis and reflects physiology of nerve roots better than the limb electromyography.

Predictors of refractoriness in a Turkish status epilepticus data bank.

Refractory status epilepticus (RSE) is known to constitute approximately 10-50% of all cases of status epilepticus (SE) and is associated with significant morbidity and mortality. In the present study, data from a prospectively collected SE database were analyzed. Patients with RSE (defined as a SE episode requiring a second line of intravenous treatment following intravenous phenytoin) were compared with patients with nonrefractory SE (NRSE); 290 episodes of SE were identified, of which 108 (38%) were defined as RSE. Univariate analysis revealed that age, female gender, SE type, SE duration, and acute etiology were associated with refractoriness, whereas electroencephalographic patterns were not. Nonconvulsive SE, which is probably associated with delays in treatment initiation, was a predictor of RSE, although it was not retained as a predictor in multivariate analysis. In the latter analysis, female gender (odds ratio: 1.815, 95% CI: 1.053-3.126) and acute etiology (odds ratio: 0.619, 95% CI: 0.429-0.894) were shown to be the only significant independent predictors of refractoriness.

Determination of nerve conduction abnormalities in patients with impaired glucose tolerance.

Recent studies have shown that impaired glucose tolerance (IGT) is associated with dysfunction in the peripheral and autonomic nerves. The aim of this study was to determine the electrophysiological abnormalities of IGT. To determine electrophysiological abnormality in the large sensorimotor and sudomotor autonomic nerves with IGT patients, 43 patients and 34 healthy subjects have been studied. Subjective neuropathy symptoms, neurological examination and the electrophysiological findings were evaluated. When conduction of large somatic fibers only was evaluated, the ratio of electrophysiological abnormality was found to be 21%. In addition, where sympathetic skin response was evaluated the sudomotor autonomic abnormality ratio was 28% in upper extremities, 53% in lower extremities, and 16% in upper and lower extremities together. The percentages of abnormal electrophysiological parameters in different motor and sensory nerves were 39.5% in the peroneal motor nerve, 20.9% in the median motor and sural sensory nerves, 18.6% in the median sensory nerve, 16.3% in the tibial motor nerve, 14% in the ulnar sensory nerve, and 2.3% in the ulnar motor nerve. While distal motor latency was the most frequent abnormal parameter in the median and tibial motor nerves, the amplitude changes in the peroneal and ulnar motor nerves were also prominent. In sensory evaluation, the onset latency in the median-ulnar sensory nerves and the amplitude in the sural sensory nerve were found to be evident abnormalities.

Visual evoked potentials in differential diagnosis of multiple sclerosis and neurobehcet's disease.

Behcet's disease, a multisystemic vascular inflammatory disorder of unknown origin, is relatively rare and central nervous system involvement is seen in 5% of affected individuals. This form of the disease, called as neurobehcet's disease (NB), can be misdiagnosed as multiple sclerosis (MS), a demyelinating disorder of central nervous system, so their differential diagnosis is important. In this study, to identify the parameters of electrophysiological testing that might be useful in their differential diagnosis, we performed evoked potentials (EPs) and electroneuromyography (ENMG) on patients with MS and NB, and on normal volunteers. A total of 95 persons, 55 MS patients, 20 NB patients and 20 normal volunteers between ages 31 and 55, were studied electrophysiologically. Visual evoked potential (VEP), brainstem auditory evoked potential (BAEP), posterior tibial somatosensory evoked potential (SEP) and nerve conduction and needle electromyography studies were performed on all patients and volunteers. All parameters of EPs were compared among the groups. The results of the BAEP and SEP studies did not show statistically significant difference between NB and MS. However, the VEP study indicated that the amplitude values of cortical VEP potentials (P100) in the NB and MS groups were lower than those of the normal group (p < 0.01), and that the amplitudes in the NB group were lower than for the MS group (p < 0.05). Therefore, P100 amplitude measured from peak to peak seems to be more reliable and thus should be used in the differential diagnosis of MS and NB.