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.

Occurrence and severity of myasthenic crisis in an unselected Turkish cohort of patients with myasthenia gravis.

Myasthenia gravis (MG) is a disorder of the neuromuscular junction that can deteriorate into myasthenic crisis, involving weakness of bulbar and respiratory muscles. In this study, we describe the clinical manifestations of myasthenic crisis, identify risk factors, and examine treatments and outcomes. All 95 patients with generalized MG treated at our center during the last 10 years were included in this retrospective study. We collected data from the patients' records, including clinical follow-ups, muscle antibodies, thymic status, and treatments. The characteristics of patients who did and did not experience myasthenic crisis were compared. Features of all myasthenic crises were also assessed. Twelve patients (13%) developed myasthenic crisis during the observation period. Men were more often affected at older ages. Seven patients experienced multiple myasthenic crises. Thymoma increased the risk of a crisis, whereas thymic hyperplasia decreased the risk. Myasthenic crises were more common in the summer months. No patients died during a myasthenic crisis. Risk factors for myasthenic crisis were thymoma, older age, MuSK antibodies, and previous crises. Individualized and active immunosuppressive treatment and optimal intensive care during crises provide a good outcome for patients with generalized MG.

Birth outcomes in pregnant women with epilepsy: A Nationwide multicenter study from Türkiye.

OBJECTIVE: The present study was aimed at investigating the effects of anti-seizure medications (ASMs), patient demographic characteristics, and the seizure type and frequency on the development of congenital malformations (CMs) in the infants of pregnant women with epilepsy (PWWE). METHODS: PWWE followed up at the neurology outpatient clinic of 21 centers between 2014 and 2019 were included in this prospective study. The follow-up of PWWE was conducted using structured, general pregnant follow-up forms prepared by the Pregnancy and Epilepsy Study Committee. The newborns were examined by a neonatologist after delivery and at 1 and 3 months postpartum. RESULTS: Of the infants of 759 PWWE, 7.2% had CMs, with 5.6% having major CMs. Polytherapy, monotherapy, and no medications were received by 168 (22.1%), 548 (72.2 %), and 43 (5.7 %) patients, respectively. CMs were detected at an incidence of 2.3% in infants of PWWE who did not receive medication, 5.7% in infants of PWWE who received monotherapy, and 13.7% in infants of PWWE who received polytherapy. The risk of malformation was 2.31-fold (95% confidence interval (CI): 1.48-4.61, p < .001) higher in infants of PWWE who received polytherapy. Levetiracetam was the most frequently used seizure medication as monotherapy, with the highest incidence of CMs occurring with valproic acid (VPA) use (8.5%) and the lowest with lamotrigine use (2.1%). The incidence of CMs was 5% at a carbamazepine dose <700 mg, 10% at a carbamazepine dose ≥700 mg, 5.5% at a VPA dose <750 mg, and 14.8% at a VPA dose ≥750 mg. Thus the risk of malformation increased 2.33 times (p = .041) in infants of PWWE receiving high-dose ASMs. SIGNIFICANCE: Birth outcomes of PWWE receiving and not receiving ASMs were evaluated. The risk of CMs occurrence was higher, particularly in infants of PWWE using VPA and receiving polytherapy. The incidence of CMs was found to be lower in infants of PWWE receiving lamotrigine.

The rare rs769301934 variant in NHLRC1 is a common cause of Lafora disease in Turkey.

Lafora disease (LD) is a severe form of progressive myoclonus epilepsy inherited in an autosomal recessive fashion. It is associated with biallelic pathogenic variations in EPM2A or NHLRC1, which encode laforin and malin, respectively. The disease usually starts with adolescent onset seizures followed by progressive dementia, refractory status epilepticus and eventually death within 10 years of onset. LD is generally accepted as having a homogenous clinical course with no considerable differences between EPM2A or NHLRC1 associated forms. Nevertheless, late-onset and slow progressing forms of the disease have also been reported. Herein, we have performed clinical and genetic analyses of 14 LD patients from 12 different families and identified 8 distinct biallelic variations in these patients. Five of these variations were novel and/or associated with the LD phenotype for the first time. Interestingly, almost half of the cases were homozygous for the rare rs769301934 (NM_198586.3(NHLRC1): c.436 G > A; p.(Asp146Asn)) allele in NHLRC1. A less severe phenotype with an onset at a later age may be the reason for the biased inflation of this variant, which is already present in the human gene pool and can hence arise in the homozygous form in populations with increased parental consanguinity.

Epilepsy in patients with familial hemiplegic migraine.

OBJECTIVE: The coexistence of epilepsy in familial hemiplegic migraine (FHM) has not been reviewed systematically. We investigated the associations of epilepsy in patients with FHM with CACNA1A, ATP1A2, SCN1A or PRRT2 mutations along with clinical and genetic data. MATERIALS AND METHODS: We performed a search in the PubMed bibliographic database and the Cochrane Library was screened for eligible studies, from April 1997 to December 2020. Additionally, Online Mendelian Inheritance in Man (OMIM) was searched for mutations in the CACNA1A, ATP1A2, SCN1A and PRRT2 genes. Brief reports, letters, and original articles about FHM and epilepsy were included in the review if their mutations and clinical course of diseases were identified. RESULTS: Of the included patients with FHM whose information could be accessed, there were 28 families and 195 individuals, 78 of whom had epilepsy; 30 patients had focal epilepsy and 30 patients had generalized epilepsy. All mutations except ATP1A2, which could not be evaluated due to insufficient data, revealed first epilepsy then HM. In 60 patients for whom the epilepsy prognosis was evaluated, only 3.5% of patients were drug-resistant, and the remainder had a self-limited course or responded to anti-epileptic drug treatment. CONCLUSION: Mutations in all three and possibly four FHM genes can cause epilepsy. Contrary to our expectations, the well-known epilepsy gene SCN1A mutations are not the leading cause; the highest number of cases associated with epilepsy belongs to the ATP1A2 mutation. Drug-resistant forms of epilepsy are rare in all FHM mutations, and this information is important for counseling patients.

Role of thymus on prognosis of myasthenia gravis in Turkish population.

OBJECTIVE: Myasthenia gravis (MG) is an autoimmune disease that may cause a disorder in transmission at the neuromuscular junction. Antibodies directed against acetylcholine receptors are responsible. The thymus is the place that that production of these antibodies mainly occurs. The thymus gland abnormalities and abnormal production of these antibodies are associated with MG. Consequently, thymectomy is a common treatment for MG. The nature of the disease makes it difficult to plan prospective, controlled trials; therefore, there is no current consensus among clinicians on a single algorithm of treatment, and the approach is frequently based on the observations and experiences of experts. The contributions to the literature largely consist of retrospective studies examining an approach to treatment and the effects of thymectomy on prognosis. In this retrospective study, evaluation of Turkish patients with myasthenia gravis was carried out for the importance of thymectomy and effects on prognosis. METHODS: In this study, 93 patients with myasthenia gravis whose followed up at Neuromuscular outpatient clinic between 1998-2018 were evaluated retrospectively. Type of disease, antibody status, treatment, thymectomy, thymus pathology and prognosis were assessed. RESULTS: Thymectomy had been a positive effect on the prognosis of the disease independent of the duration of disease and thymic pathology. The best results had been obtained with early thymectomy with short disease duration, younger age and patients with thymic hyperplasia. Success of therapy was limited with thymoma. With advanced age need for thymectomy was decreased. CONCLUSION: In the present study, evaluation of 93 patients with myasthenia gravis was done retrospectively and it was concluded that thymectomy had a positive effect on prognosis, especially in young patients when performed as early as possible. The most successful results were obtained in cases with thymic hyperplasia.

Optimum recording time of routine electroencephalogram for adults with epilepsy

Background/aim: This study aimed to reveal the optimum recording time of routine electroencephalogram (EEG) for adults with epilepsy. Materials and methods: In this clinical observational study we investigated features of paroxysms that emerged in EEGs recorded for 45 min in adults with epilepsy. Results: Paroxysms were detected in 38.14% of 97 patients. The probability of occurrence of paroxysm during the first 10 min was found to be statistically significantly low in comparison to the first 30 and 45 min (respectively P = 0.004, P = 0.0001). This probability was found to increase insignificantly when comparing the first 20 min with the first 30 min (P = 0.125), but it increased significantly in comparison to 45 min (P = 0.008). On the other hand, this probability was found to increase insignificantly when comparing the first 30 min with the first 45 min (P = 0.125). The cutoff point to specify the existence of interictal epileptiform discharges in the ROC analysis was found to be ≤39 min (95% CI: 0.958­1.000), and 90% of interictal epileptiform discharges were revealed during the first 30 min of EEG recording. Conclusion: The recording time of routine EEGs for adults with epilepsy should not be less 30 min.

Clinical, neuroradiological, and electroencephalographic findings of reflex epilepsies

Background/aim: Reflex seizures are defined as epilepsies with seizures induced by a specific afferent stimulus or patient activity alone or in combination with spontaneous seizures, and/or accompanied by photoparoxysmal response on electroencephalogram (EEG). The aim of this study is to review and analyze clinical, neuroradiological, and EEG findings in reflex epilepsies. Materials and methods: The records of 1598 follow-up patients out of 2237 patients who had been examined between July 1995 and August 2017 were analyzed retrospectively. Results: Eighty of 1598 patients had reflex epilepsy and 72 of those patients had seizures induced by visual stimuli. Considering the somatosensory stimuli, in one patient it was associated with eating while in 7 patients it was associated with hot water. The results of neurological examination were normal in 90% while cranial imaging was normal in 82.5% of the patients. Only 53 of 80 patients' EEGs revealed pathological EEG findings. Furthermore, in 43 patients, the most frequently prescribed drug was valproate. Conclusion: In this hospital-based study, reflex epilepsy frequency was 5% and cranial imaging was mostly found to be normal, as stated in the literature. However, patient histories revealed an unexpectedly high rate of head trauma before seizure onset and a family history of epilepsy.

A database for screening and registering late onset Pompe disease in Turkey.

The aim of this study was to search for the frequency of late onset Pompe disease (LOPD) among patients who had a myopathy with unknown diagnosis registered in the pre-diagnostic part of a novel registry for LOPD within a collaborative study of neurologists working throughout Turkey. Included in the study were 350 patients older than 18 years who have a myopathic syndrome without a proven diagnosis by serum creatine kinase (CK) levels, electrodiagnostic studies, and/or muscle pathology, and/or genetic tests for myopathies other than LOPD. Acid alpha glucosidase (GAA) in dried blood spot was measured in each patient at two different university laboratories. LOPD was confirmed by mutation analysis in patients with decreased GAA levels from either both or one of the laboratories. Pre-diagnostic data, recorded by 45 investigators from 32 centers on 350 patients revealed low GAA levels in a total of 21 patients; from both laboratories in 6 and from either one of the laboratories in 15. Among them, genetic testing proved LOPD in 3 of 6 patients and 1 of 15 patients with decreased GAA levels from both or one of the laboratories respectively. Registry was transferred to Turkish Neurological Association after completion of the study for possible future use and development. Our collaborative study enabled collection of a considerable amount of data on the registry in a short time. GAA levels by dried blood spot even from two different laboratories in the same patient may not prove LOPD. LOPD seemed to be rarer in Turkey than in Europe.

An association analysis at 2q36 reveals a new candidate susceptibility gene for juvenile absence epilepsy and/or absence seizures associated with generalized tonic-clonic seizures.

PURPOSE: To further evaluate the previously shown linkage of absence epilepsy (AE) to 2q36, both in human and WAG/Rij absence rat models, a 160-kb region at 2q36 containing eight genes with expressions in the brain was targeted in a case-control association study involving 205 Turkish patients with AE and 219 controls. METHODS: Haplotype block and case-control association analysis was carried out using HAPLOVIEW 4.0 and inhibin alpha subunit (INHA) gene analysis by DNA sequencing. KEY FINDINGS: An association was found between the G allele of rs7588807 located in the INHA gene and juvenile absence epilepsy (JAE) syndrome and patients having generalized tonic-clonic seizures (GTCS) with p-values of 0.003 and 0.0002, respectively (uncorrected for multiple comparisons). DNA sequence analysis of the INHA gene in 110 JAE/GTCS patients revealed three point mutations with possible damaging effects on inhibin function in three patients and the presence of a common ACTC haplotype (H1) with a possible dominant protective role conferred by the T allele of rs7588807 with respective p-values of 0.0005 and 0.0014. SIGNIFICANCE: The preceding findings suggest that INHA could be a novel candidate susceptibility gene involved in the pathogenesis of JAE or AE associated with GTCS.

Ross syndrome: Unilateral hyperhidrosis, Adie's tonic pupils and diffuse areflexia.

Ross syndrome is a rare disorder first described in 1958 with partial autonomic dysfunction. It has three basic components including unilateral or bilateral segmental anhidrosis, Adie's tonic pupils and areflexia or hyporeflexia of deep tendon reflexes. The most disturbing symptom in the patients is segmental compensatory hyperhidrosis and often the hypohidrosis or anhidrosis is not even noticed. While the pathogenesis of Ross syndrome is unclear, degenerative changes or damage to the peripheral autonomic nerve system or dorsal root ganglia have been suggested as possible causes. About 50 cases have been reported, usually by neurologists and ophthalmologists, and less often by dermatologists. We present a 26-year-old patient who displayed the classic triad of this syndrome, emphasizing that the presenting complaint may be hyperhidrosis and that multidisciplinary evaluation in neurology and ophthalmology is essential.

Electrodiagnosis of ulnar nerve entrapment at the elbow.

OBJECTIVE: To evaluate the different localizing electrodiagnostic techniques of ulnar nerve entrapment at the elbow (UNE), particularly, comparison of the sensitivities of long segment stimulation across the elbow, versus short segment stimulation. METHODS: Patients who were referred to the Neurophysiology Laboratory of Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey between 2000-2004 with a preliminary diagnosis of UNE were retrospectively evaluated. We compared the sensitivity of studying long segments (8-12 cm) versus short segments (3 cm) for the diagnosis of UNE in 93 limbs. RESULTS: The study group consisted of 55 females and 31 males. Slowing of the conduction velocity (<50 m/sn) across the elbow was recorded in 48.4% of the limbs with long segment studies, and 73% of the limbs with short segment studies. In 82% of cases, an amplitude drop of the compound muscle action potential (CMAP) was also recorded. A CMAP amplitude drop of 10-30% between the wrist and elbow was recorded in 35 limbs (37.6%), while a drop of more than 50% was only recorded in 5 limbs (5.4%). CONCLUSION: Short segment studies are sensitive for the electrodiagnosis of UNE, and although a CMAP amplitude drop is recorded in most patients, an amplitude drop consistent with a conduction block (>50%) is rare.