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.

Corneal nerve fiber involvement in chronic inflammatory demyelinating polyneuropathy.

BACKGROUND: Despite the primary myelin-related pathophysiology, small fiber neuropathy (SFN) and axonal degeneration are also considered to be involved and associated with disabling symptoms and impaired quality of life in chronic inflammatory demyelinating polyneuropathy (CIDP). Demonstration of SFN usually requires complex or invasive investigations. OBJECTS: In vivo corneal confocal microscopy (IVCCM) has evolved as a non-invasive, easily applied method for quantification of small fiber involvement in peripheral nerve disorders. We aimed to investigate the potential role of IVCCM in CIDP. METHODS: In this cross-sectional study, 15 patients with CIDP underwent assessment with clinical disability scales, neuropathic pain (NP) and autonomic symptom questionnaires, nerve conduction studies, and IVCCM. IVCCM parameters were analyzed and compared to those from 32 healthy controls. RESULTS: Corneal nerve fiber density (CNFD) and corneal nerve fiber length (CNFL) were significantly decreased in the CIDP group, compared to those in controls (p = 0.03 and p = 0.024, respectively). Langerhans cells and fiber tortuosity were increased in CIDP patients (p = 0.005 and p = 0.001, respectively). IVCCM parameters were significantly lower in patients with NP compared to those in patients without NP. CONCLUSION: IVCCM shows promise as a non-invasive complementary biomarker in the assessment of demyelinating polyneuropathies, providing insights into the potential pathophysiology of these non-length-dependent neuropathies.

Reference jitter values for the sternocleidomastoid muscle with concentric needle electrodes.

BACKGROUND: The aim of this study was to establish reference jitter values for the voluntary activated sternocleidomastoid (SCM) muscle using a concentric needle electrode (CNE). METHODS: The study included 39 healthy participants (20 female and 19 male) aged 18-77 y. Jitter was expressed as the mean consecutive difference (MCD) of 80-100 consecutive discharges. Filters were set at 1 and 10 kHz. The mean MCDs for all participants were pooled, and the mean value +2.5 SD was accepted as the upper limit for the mean MCD. The upper limit for individual MCD was calculated using +2.5 SD of the upper 10th percentile MCD for individual participants. RESULTS: Mean age of the participants was 45 ± 14.5 y. Mean MCD was 16.20 ± 2.23 µs (range: 12-21 µs), and the upper limit of normal for mean MCD was 21.8 µs. The mean value for 823 individual jitters was 23.3 ± 4.61 µs (range: 6.6-36.9 µs), and the upper limit of normal for each individual jitter was 34.6 µs. CONCLUSIONS: The present findings indicate that upper normal limit for mean MCD is 22 µs and for individual data it is 35 µs.

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).

Cutaneous silent period in myofascial pain syndrome.

INTRODUCTION: An increased response to painful stimuli without spontaneous pain suggests a role of central hyperexcitability of pain pathways in the pathogenesis of myofascial pain syndrome (MPS). In this study we aimed to test the hypothesis that spinal pain pathways are affected in MPS. We used cutaneous silent period (CSP) parameters to demonstrate the hyperexcitability of spinal pain pathways in MPS. METHODS: Twenty-nine patients diagnosed with MPS and 30 healthy volunteers were included in the study. The CSP recordings were performed in the right upper and left lower extremities. RESULTS: In both upper and lower extremities, patients had prolonged CSP latencies (P = 0.034 and P = 0.049 respectively) and shortened CSP durations (P = 0.009 and P = 0.008, respectively). DISCUSSION: Delayed and shortened CSP in MPS patients implies dysfunction in the inhibitory mechanism of the spinal/supraspinal pain pathways, suggesting central sensitization in the pathogenesis of MPS and supporting our research hypothesis. Muscle Nerve 57: E24-E28, 2018.

Ulnar nerve entrapment at elbow in obstructive sleep apnea patients: a randomized controlled trial.

PURPOSE: Obstructive sleep apnea (OSA) is a highly prevalent disease. For diagnostic and therapeutic purposes, OSA has been divided into several subgroups. Positional OSA (POSA), the most frequent subgroup (56 %), is described as overall apnea hypopnea index (AHI) ≥5 and supine AHI at least twice as high when compared to non-supine AHI. We aimed to investigate the frequency of ulnar nerve entrapment neuropathy at the elbow (UNEE) in OSA patients without clinical signs and symptoms of ulnar neuropathy and intended to find if sleeping position in OSA had an impact on UNEE development. METHODS: Fifty POSA, 48 non-positional OSA (NPOSA) patients, and 45 healthy controls without diabetes mellitus, hypothyroidism, rheumatic diseases, and cervical radiculopathy underwent nerve conduction studies. RESULTS: We found that UNEE was highly frequent in OSA patients (42.9 %) and significantly more frequent in moderate to severe POSA patients than mild POSA patients (65.4 vs. 33.3 %, p < 0.05). Furthermore, when compared to non-positional ones, UNEE was significantly more frequent in moderate to severe POSA patients (65.4 vs. 36.4 %, p < 0.05). CONCLUSIONS: Our results showed that the severity of OSA in positional patients was correlated with increased frequency of UNEE. OSA patients should be informed about the predisposition of UNEE and questioned for the symptoms in periodical controls. POSA patients should be alerted about the additional effect of sleeping position on UNEE and the necessity of OSA treatment should be emphasized.

Somatosensory evoked potentials as a screening tool for diagnosis of spinal pathologies in children with treatment refractory overactive bladder.

PURPOSE: To evaluate the usefulness of somatosensory evoked potential as a screening tool for spinal pathologies in patients with treatment refractory overactive bladder. METHODS: This prospective study was performed between January 2011 and January 2014. Children >5 years old with treatment refractory overactive bladder were enrolled after exclusion of anatomical and neurological causes of incontinence. All patients underwent urodynamic studies, spinal MRI, and somatosensory evoked potential (SEP). Sensitivity, specificity, PPV, and NPV were calculated for SEP. RESULTS: Thirty-one children (average age 8.3 ± 2.9 years) were included in the study. SEP was abnormal in 13 (41.9%), and MRI was abnormal in 8 (25.8%) patients. SEP was found to have a sensitivity of 87.5%, a specificity of 73.9%, positive predictive value of 53.85%, and negative predictive value (NPV) of 94.4%. CONCLUSION: In patients with treatment refractory OAB, SEP is an important tool for the screening of tethered cord/spinal pathologies. Our results suggest that a child with a normal SEP study in this group of patients may not require further investigation with MRI.

Medial plantar-to-radial amplitude ratio: does it have electrodiagnostic utility in distal sensory polyneuropathy?

PURPOSE OF THE STUDY: We proposed a new electrophysiological parameter medial plantar (MP)-to-radial amplitude ratio (MPRAR), similar to sural-to-radial amplitude ratio (SRAR), in the diagnosis of distal sensory polyneuropathy (DSP), based on the concept that distal nerves are affected more and earlier than proximal nerves in axonal neuropathies. We aimed to investigate the diagnostic sensitivity of this parameter in diabetic DSP, together with sensitivities of SRAR and MP nerve action potential (NAP) amplitude. MATERIALS AND METHODS: In 124 healthy controls and 87 diabetic patients with clinically defined DSP and normal sural responses, we prospectively performed sensory nerve conduction studies (NCS), and evaluated the MP NAP amplitude, MPRAR and SRAR values. We determined the lower limits of normal (LLN) of these parameters in the healthy controls and calculated their sensitivities and specificities in detecting DSP in diabetic patients. RESULTS: MP nerve amplitude and MPRAR values were significantly lower in the patient group, compared to controls. However, SRAR values did not differ significantly between the two groups. The LLN of MP NAP amplitude was found to be 4.1 µV. The cutoff values for SRAR and MPRAR were determined as 0.24 and 0.16, respectively. MPRAR was abnormal in 21.8% of patients. However, the most sensitive parameter in detection of DSP was MP NAP amplitude, which showed a sensitivity of 31% and a specificity of 100%. CONCLUSIONS: Although MPRAR is more sensitive than SRAR in detecting DSP, it does not provide additional diagnostic yield to the assessment of MP NCS alone in diabetic DSP patients with normal sural responses.

Exome sequencing reveals homozygous TRIM2 mutation in a patient with early onset CMT and bilateral vocal cord paralysis.

Charcot-Marie-Tooth disease is a heterogeneous group of inherited distal symmetric polyneuropathies associated with mutations in genes encoding components essential for normal functioning of the Schwann cell and axon. TRIM2, encoding a ligase that ubiquitinates the neurofilament light chain, was recently associated with early-onset neuropathy in a single patient. We report a TRIM2 homozygous missense mutation (c.2000A>C; p.D667A) in a patient with peripheral neuropathy and bilateral vocal cord paralysis, allowing for further delineation of the associated phenotypic spectrum.

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.

Expert opinion on the diagnostic odyssey and management of late-onset Pompe disease: a neurologist's perspective.

This consensus statement by a panel of neurology experts aimed to provide a practical and implementable guidance document to assist clinicians with the best clinical practice in terms of diagnosis, treatment, and monitoring of late-onset Pompe disease (LOPD). The participating experts consider the clinical suspicion of LOPD by the physician to be of utmost importance in the prevention of diagnostic and therapeutic delay in LOPD patients. A diagnostic algorithm is proposed to facilitate the diagnosis of LOPD in patients presenting with unexplained proximal/axial weakness (with or without respiratory symptoms) or restrictive respiratory insufficiency with hyperCKemia and/or exercise intolerance as the red flag symptoms/signs that raise the index of suspicion for LOPD diagnosis. The diagnosis is based on the subsequent use of dried blood spot (DBS) assay, and the DBS assay can be confirmed by acid alpha-glucosidase (GAA) tissue analysis in leukocytes, fibroblasts, or muscle fibers and/or genetic mutation analysis. Accordingly, experts consider increased awareness among physicians about potential presenting characteristics with a high index of suspicion for LOPD to be crucial to suspect and consider LOPD in the differential diagnosis, while strongly suggesting the use of a diagnostic algorithm combined with DBS assay and confirmatory tests in the timely diagnosis of LOPD and implementation of best practice patterns.

Physical and mental fatigue in myasthenia gravis and its correlation with other symptoms.

INTRODUCTION: Muscle weakness and easy fatigability are the clinical hallmarks of myasthenia gravis (MG). However, fatigue perception, which can be seen quite often in myasthenic patients, and its effect on the quality of life, irrespective of motor deficit, has not been elucidated yet. The aim is to evaluate the frequency of fatigue in myasthenic patients with nearly full muscle strength and the effect of fatigue on quality of life by assessing its correlation with other symptoms. METHODS: Fifty-three patients with ocular or mild generalized MG in remission or minimal manifestations completed the questionnaires measuring the severity of MG and quality of life (MG Composite Scale and MG-Activities of Daily Living Profile). Both patient group and control group (53 healthy volunteers)completed the scales assessing fatigue [Fatigue Assessment Scale (FAS) and Fatigue Impact Scale (FIS)], depression [Beck Depression Inventory (BDI)] and sleep (Epworth Sleepiness Scale). Disease severity was assessed using MG Foundation of America (MGFA) and MGFA Post-Intervention Status classifications. RESULTS: FAS, FIS physical and BDI scores were significantly higher in patients compared to the control group (p = 0.003, p = 0.001, and p = 0.003, respectively) and fatigue was associated with depression and daytime sleepiness. Inpatient group, depressive symptoms and daytime sleepiness were higher in females (p = 0.019 and p = 0.013). The mean values of FIS total and cognitive scores were higher in patients with generalized MG (p = 0.033 and p = 0.045). Fatigue scores correlated with motor signs. DISCUSSION: Fatigue can be seen in MG independently from muscle weakness and is an important symptom worsening the quality of life.

Accuracy and reliability of magnetic resonance imaging in the diagnosis of idiopathic intracranial hypertension.

PURPOSE: To determine the diagnostic utility of brain magnetic resonance imaging (MRI) findings in patients with idiopathic intracranial hypertension (IIH) and to investigate the significance of evaluating radiological findings together with neurological and ophthalmological data in the diagnosis of IIH. MATERIALS AND METHODS: All consecutive patients diagnosed with IIH in our tertiary neuro-ophthalmology center between January 1, 2018 and March 15, 2020, were included in the study. The clinical, radiological, and ophthalmological findings of IIH patients were compared with the control group with similar demographic characteristics. RESULTS: A total of 98 patients, 49 cases and 49 controls, were included in the study. Lateral ventricular index had the highest area under the curve (AUC) value (0.945) for prediction of disease group followed by sella height category (AUC = 0.915) and optic nerve tortuosity (AUC = 0.855) According to the multivariate model we developed, caudate index (OR = 0.572, 95% CI 0.329-0.996), lateral ventricle index (OR = 3.969, 95% CI 1.851-8.509) and bilateral optic nerve tortuosity (OR = 22,784, 95% CI 2.432-213.450) were significant predictors for disease group. CONCLUSION: Tortuosity in the optic nerve, lateral ventricular index and caudate index can be used as MRI parameters supporting the diagnosis of IIH in clinically suspicious cases. A holistic approach to the clinical and radiological findings of the cases in the diagnosis of IIH can prevent overdiagnosis and enable early correct diagnosis.

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.

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.

Impact of obstructive sleep apnea on neuromuscular transmission- a descriptive study.

Objective: Obstructive sleep apnea (OSA) is a sleep disorder accompanied by intermittent hypoxia. Neuromuscular transmission (NT) is known to be disturbed under chronic hypoxia. In this descriptive study, it has been aimed to test NT under intermittent hypoxia in OSA. Methods: Thirty-nine newly diagnosed OSA patients without any comorbidities or conditions that alter NT were included in the study. Jitter analysis was performed using a concentric needle electrode. Results: The mean jitter value of 39 OSA patients was 25.9 ± 3.7 µs. When compared to the mean reference jitter values, patients in the present study had significantly higher jitter (p < 0.001). Seven (17.9%) patients met the electrophysiological criteria for NT failure. Conclusion: The authors propose that intermittent hypoxia can be the trigger for NT failure in OSA. The interaction between increased oxidative stress and disturbed mitochondrial functions may also contribute.