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.

Iatrogenic systemic botulism after intragastric botulinum neurotoxin injection: Case report.

BACKGROUND AND PURPOSE: The recent off-label use of botulinum neurotoxin (BoNT) for intragastric obesity treatment has led to 67 cases of systemic botulism in Türkiye, Germany, Austria and Switzerland. This case report highlights the potential risks and adverse effects associated with this treatment. CASE REPORT: A 36-year-old female presented to the emergency room with shortness of breath, fatigue, difficulty in eating and holding her head, constipation and double vision after receiving intragastric BoNT injection for obesity treatment. She had bilateral orbicularis oculi weakness, facial diplegia, weak tongue, masseter, neck and extremity muscles. Electromyography showed a presynaptic type neuromuscular junction disorder. The patient was admitted to the intensive care unit and administered botulinum heptavalent equine-derived antitoxin, but the medication had to be stopped due to a reaction. The patient was started on pyridostigmine for symptomatic treatment and was transferred to an inpatient clinic after minimal improvement. She was discharged after 7 days of follow-up. CONCLUSION: Clinicians should be cautious of the potential risks of intragastric BoNT injection for obesity treatment and consider systemic botulism as a potential adverse effect. Antitoxin treatment should be considered in clinically progressing patients despite negative botulinum toxin testing.

IVIg-induced headache: prospective study of a large cohort with neurological disorders.

BACKGROUND: Intravenous immune globulin (IVIg) is frequently used in some neurological diseases and is also the first-line therapy in Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, and multifocal motor neuropathy. We aimed to evaluate the frequency and characteristics of headaches, which is one of the most common side effects of IVIg treatment. METHODS: Patients who received IVIg treatment for neurological diseases were prospectively enrolled in 23 centers. Firstly, the characteristics of patients with and without IVIg-induced headaches were analyzed statistically. Then, patients with IVIg-induced headaches were classified into three subgroups determined by their history: no primary headache, tension-type headache (TTH), and migraine. RESULTS: A total of 464 patients (214 women) and 1548 IVIg infusions were enrolled between January and August 2022. The frequency of IVIg-related headaches was 27.37% (127/464). A binary logistic regression analysis performed with significant clinical features disclosed that female sex and fatigue as a side effect were statistically more common in the IVIg-induced headache group. IVIg-related headache duration was long and affected daily living activities more in patients with migraine compared to no primary headache and TTH groups (p = 0.01, respectively). CONCLUSION: Headache is more likely to occur in female patients receiving IVIg and those who develop fatigue as a side effect during the infusion. Clinicians' awareness of IVIg-related headache characteristics, especially in patients with migraine, may increase treatment compliance.

Assessment of the Clinical Use of Vestibular Evoked Myogenic Potentials and the Video Head Impulse Test in the Diagnosis of Early-Stage Parkinson's Disease.

OBJECTIVES: To explore the usefulness of vestibular tests including "vestibular evoked myogenic potentials" (VEMPs) and the video head impulse test (vHIT) in the early diagnosis of "idiopathic Parkinson's disease" (PD). MATERIALS AND METHODS: The study involved 80 participants including 40 patients (24 males, 16 females; age average 63.20 ± 7.94 years) with PD and 40 healthy individuals (18 males and 22 females; age average of 60.36 ± 7.68 years). The Modified Hoehn and Yahr (H&Y) scale was used to measure how Parkinson's symptoms progress and the level of disability. Patients with PD underwent cVEMPs, oVEMPs, and vHIT and the results were compared with those of 40 age-matched healthy control (HC) subjects. vHIT results and VEMP responses were registered in all patients and HCs. RESULTS: One-sided absent cVEMP responses were found in 6 (15%) patients with PD and 8 (20%) patients had bilaterally absent responses. Five (12.5%) patients had 1-sided absent oVEMP responses and it was bilateral in 6 (15%). Patients with PD had significantly shorter cVEMP P1, N1 latency, lower cVEMP amplitudes, and oVEMP amplitudes than the HC group. The cVEMP and oVEMP amplitude asymmetry ratio was significantly higher in the PD group (P < .05). Evaluation of vHIT results and vestibular-ocular reflex (VOR) gain between the groups revealed that anterior canal and posterior canal VOR gains results were remarkably lower in the PD group than in the HCs (P < .05). There was no difference in right and left lateral canal VOR gains between the groups (P > .05). CONCLUSION: The results of this study suggest that cVEMP and vHIT can be used to evaluate the vestibular system in patients with early-stage Parkinson's disease.

Dehiscence or thinning of bone overlying the superior semicircular canal in idiopathic intracranial hypertension.

STUDY DESIGN: Retrospective cohort. OBJECTIVES: The objective of the study is to evaluate a relationship between idiopathic intracranial hypertension (IIH) and superior semicircular canal dehiscence (SSCD) of bone overlying the superior semicircular canal (SSC). MATERIALS AND METHODS: A total of 57 (114 ears) individuals, 20 of whom were controls and 37 of whom were IIH, were included in the study. Individuals were evaluated with 0.8 mm slice thickness computed tomography (CT) images for SSC bony roof thickness and SSCD. Thickness of the bony roof over the SSC was graded from Grade 1 to Grade 4. Grade 3 was defined as pre-dehiscence and Grade 4 as dehiscence. RESULTS: Bony roof thickness was 1.25 mm in the control group and 0.76 mm in the IIH group. When bony roof thickness was compared between the groups, it was found to be significantly thinner in the IIH group (p = 0.012). In the IIH group, while dehiscence was detected in 25 of 74 ears, no dehiscence was detected in 49 ears. In the control group, while dehiscence was detected in 5 ears, no dehiscence was detected in 35 ears. The difference is statistically significant (p = 0.015). The correlation between bony roof thickness and cerebrospinal fluid (CSF) pressure in the IIH group was not statistically significant (p = 0.343; rho = 0.110). The correlation between bony roof thickness and age in the IIH group was not statistically significant (p = 0.082; rho = - 0.164). CONCLUSION: Increased CSF pressure in patients with IIH may cause chronic, progressive, and irreversible damage to the bone of the SSC and, according to our study, the rate of SSCD was found to be high in IIH patients.

The impact of myasthenia gravis on lower urinary tract functions.

AIM: To assess the functions of the lower urinary tract (LUT) in patients with myasthenia gravis (MG). MATERIALS AND METHODS: A total of 36 patients (18 males and 18 females) with MG and 29 healthy controls were enrolled. Participants completed a 3-day voiding diary and responded to questionnaires "Overactive Bladder Symptom Score" (OABSS) and "International Consultation on Incontinence-Short Form" (ICIQ-SF). All patients underwent uroflowmetry and ultrasonography (US). The data were compared based on the onset of disease and serological status. RESULTS: The most common urinary symptoms were nocturia (80.5%), incontinence (61%) and urgency (47%). OABSS was higher in patients than controls (P = .008). Duration of urinary symptoms was longer, and nocturia was more common in late-onset MG (LOMG) than in early-onset MG (EOMG; P = .029, P = .023). The duration of disease and urinary symptoms statistically increased in ACh-Ab (-) group compared with ACh-Ab (+) group (P = .003, P = .027). Night-time urination frequency significantly increased while daytime voided volume (VV) decreased in LOMG compared with EOMG (P = .003 and P = .01). Residual volume on the US was significantly higher in LOMG than that in EOMG (P = .004). The duration of disease was positively correlated with tQmax and daytime urination frequency (P = .013, r = .48; P = .016, r = .398). A negative association was found between duration of disease and daytime VV (P = .04, r = -.344). CONCLUSION: LUT dysfunction may manifest disease in MG, particularly in late-onset forms. The lack of ACh-Ab seemed to prolong the duration of disease and urinary disturbances.

Ophthalmologic manifestations in myasthenia gravis: presentation and prognosis.

We investigated the ophthalmologic manifestations and factors that influence outcomes in patients with myasthenia gravis (MG). We retrospectively analyzed the prevalence of neuro-ophthalmologic findings and clinical and outcome measures of 100 consecutive patients (53 males, 47 females), aged 55.7 ± 17.5 (range 15-85) years with an established diagnosis of MG. Forty-eight patients had purely ocular symptoms at the onset of disease (OMG) and 52 patients presented with generalized symptoms (GMG). Overall, 21 patients presented with extraocular muscle (EOM) weakness. Bilateral EOM weakness was seen in 12 patients, and unilateral EOM weakness was seen in nine patients. Diplopia responded partially to immunosuppressive treatments in 60% of patients with ophthalmoparesis. Twenty-five (52.1%) patients with ocular-onset MG converted to secondary GMG at a mean time of 14.5 months. Patients who developed secondary GMG were younger and had an earlier age of disease onset when compared with patients with pure OMG (p < 0.05). Patients with secondary GMG presented more frequently with ptosis and diplopia (72% vs. 28%) compared with patients with pure ocular MG who presented more frequently with isolated ptosis (66.7% vs. 33.3%) (p = 0.02). Remission and minimal manifestation status were achieved in 50 (79.3%) of all patients with a clinical follow-up ≥ 3 years. Poor outcome was associated with the presence of thymoma (p < 0.05). Myasthenic ophthalmoparesis is bilateral and heterogeneous and partly responds to treatment with immunotherapy. Younger patients with ptosis and diplopia at disease onset had an increased risk of secondary GMG. The presence of thymoma increases the risk for poor prognosis.

Amyotrophic lateral sclerosis with coexisting cancer: a single-center study.

This study investigated the occurrence of malignancy in a cohort of patients with amyotrophic lateral sclerosis (ALS). Forty-three consecutive ALS patients (mean age 61.3 years, 31 men/12 women) admitted between 2015 and 2019 were enrolled. Clinical, electrophysiologic and outcome features that differentiate cancer-associated ALS from classical ALS were investigated. ALS was associated with cancer in 5 (11.6%) patients. Two patients were diagnosed with non-small cell lung, one with endometrium, one with prostate and one with laryngeal carcinoma. One another patient was diagnosed with monoclonal gammopathy of unknown significance, but she did not develop cancer within 12-month follow-up duration. Two patients had a previous diagnosis of cancer before the diagnosis of ALS. In the remaining 3 patients, cancer was diagnosed at the same time or after the onset of ALS. There was no significant difference with respect to mean age of onset, sex, disease duration, clinical and electrophysiological features and outcome between patients with and without malignancy. None of the patients with cancer survived more than two years after the onset of ALS except one who was diagnosed with flail-leg syndrome before the diagnosis of non-small cell lung carcinoma. ALS is not accepted as a classical paraneoplastic neurological syndrome. Although the association of ALS and cancer seems coincidental, a careful investigation for an underlying cancer is important in patients with ALS. In our patient group with cancer-associated ALS, no distinguishing features were identified.

Novel variants broaden the phenotypic spectrum of PLEKHG5-associated neuropathies.

BACKGROUND AND PURPOSE: Pathogenic variants in PLEKHG5 have been reported to date to be causative in three unrelated families with autosomal recessive intermediate Charcot-Marie-Tooth disease (CMT) and in one consanguineous family with spinal muscular atrophy (SMA). PLEKHG5 is known to be expressed in the human peripheral nervous system, and previous studies have shown its function in axon terminal autophagy of synaptic vesicles, lending support to its underlying pathogenetic mechanism. Despite this, there is limited knowledge of the clinical and genetic spectrum of disease. METHODS: We leverage the diagnostic utility of exome and genome sequencing and describe novel biallelic variants in PLEKHG5 in 13 individuals from nine unrelated families originating from four different countries. We compare our phenotypic and genotypic findings with a comprehensive review of cases previously described in the literature. RESULTS: We found that patients presented with variable disease severity at different ages of onset (8-25 years). In our cases, weakness usually started proximally, progressing distally, and can be associated with intermediate slow conduction velocities and minor clinical sensory involvement. We report three novel nonsense and four novel missense pathogenic variants associated with these PLEKHG5-associated neuropathies, which are phenotypically spinal muscular atrophy (SMA) or intermediate Charcot-Marie-Tooth disease. CONCLUSIONS: PLEKHG5-associated neuropathies should be considered as an important differential in non-5q SMAs even in the presence of mild sensory impairment and a candidate causative gene for a wide range of hereditary neuropathies. We present this series of cases to further the understanding of the phenotypic and molecular spectrum of PLEKHG5-associated diseases.

CD4+ T Cells of Myasthenia Gravis Patients Are Characterized by Increased IL-21, IL-4, and IL-17A Productions and Higher Presence of PD-1 and ICOS.

Myasthenia gravis (MG) is an autoimmune disease mediated by autoantibodies predominantly against the acetylcholine receptor (AChR). Specific T cell subsets are required for long-term antibody responses, and cytokines secreted mainly from CD4+ T cells regulate B cell antibody production. The aim of this study was to assess the differences in the cytokine expressions of CD4+ T cells in MG patients with AChR antibodies (AChR-MG) and the effect of immunosuppressive (IS) therapy on cytokine activity and to test these findings also in MG patients without detectable antibodies (SN-MG). Clinically diagnosed AChR-MG and SN-MG patients were included. The AChR-MG patients were grouped as IS-positive and -negative and compared with age- and sex-matched healthy controls. Peripheral blood mononuclear cells were used for ex vivo intracellular cytokine production, and subsets of CD4+ T cells and circulating follicular helper T (cTfh) cells were detected phenotypically by the expression of the chemokine and the costimulatory receptors. Thymocytes obtained from patients who had thymectomy were also analyzed. IL-21, IL-4, IL-10, and IL-17A productions in CD4+ T cells were increased in AChR-MG compared to those in healthy controls. IS treatment enhanced IL-10 and reduced IFN-γ production in AChR-MG patients compared to those in IS-negative patients. Increased IL-21 and IL-4 productions were also demonstrated in SN-MG patients. Among CD4+ T cells, Th17 cells were increased in both disease subgroups. Treatment induced higher proportions of Th2 cells in AChR-MG patients. Both CXCR5+ and CXCR5- CD4+ T cells expressed higher programmed cell death protein 1 (PD-1) and inducible costimulatory (ICOS) in AChR-MG and SN-MG groups, mostly irrespective of the treatment. Based on chemokine receptors on CXCR5+PD-1+ in CD4+ T (cTfh) cells, in AChR-MG patients without treatment, the proportions of Tfh17 cells were higher than those in the treated group, whereas the Tfh1 cells were decreased compared with those in the controls. The relevance of CXCR5 and PD-1 in the pathogenesis of AChR-MG was also suggested by the increased presence of these molecules on mature CD4 single-positive thymocytes from the thymic samples. The study provides further evidence for the importance of IL-21, IL-17A, IL-4, and IL-10 in AChR-MG. Disease-related CD4+T cells are identified mainly as PD-1+ or ICOS+ with or without CXCR5, resembling cTfh cells in the circulation or probably in the thymus. AChR-MG and SN-MG seem to have some similar characteristics. IS treatment has distinctive effects on cytokine expression.

Guillain Barre Syndrome: A Single Center Experience.

OBJECTIVES: To investigate the clinical, electrophysiological and epidemiological features of the patients who were diagnosed as Guillain Barre Syndrome (GBS) in our clinic. METHODS: The clinical and demographical properties of 30 patients with GBS who were hospitalized in our neurology clinic between March 2013 and August 2017 were retrospectively examined in this study. Patients were divided into two groups according to the requirement of stay in the intensive care unit (ICU). RESULTS: Patients were between 18-71 years range with 46.9 and 19.61 mean age. Seven of 30 patients (23.3%) were female, and 23 of them (76.7%) were male. Males were more dominant in the ICU (-) group (81% and 62%). A recent infection was found in 86.7% of patients. Upper respiratory tract infection (URTI) was more common in ICU (+) group whereas lower respiratory tract infection (LRTI) and acute gastroenteritis (AGE) were more common in the ICU (-) patients (p=0.007). Lower limb weakness was more frequent in the ICU (+) group (p=0.011). ICU (+) patients were lack of diplopia and dysarthria. Ataxia and dysphagia were relatively frequent in the ICU (+) group. Electrophysiological examinations revealed demyelinating polyneuropathy (26.7%), acute axonal polyneuropathy (30.1%) and acute sensorial polyneuropathy (13.3%). Demyelinating polyneuropathy was more common in the ICU (-) group, whereas acute motor and sensorial polyneuropathy (AMSAN) was more frequent in the ICU (+) group. In this study, 26.7 % of study patients required mechanical ventilation, and mortality rate was 6.8 %. CONCLUSION: URTI in ICU (+), LRTI and AGE in ICU (-) patients might be major trigger factors of GBS. Ascending weakness, dysphagia and ataxia was more frequent in ICU (+) GBS patients. Demyelinating PNP was predominant in the ICU (-) group, whereas AMSAN was more frequent in the ICU (+) patients. Multicenter randomized studies would be more useful for highlining the epidemiology of GBS.

A Case Report of A Drop Foot Developed After Common Femoral Artery Cannulation for Venoarterial Extracorporeal Membrane Oxygenation.

The drop foot cases that are associated with developing neuropathies as a result of acute compartment syndrome or femoral artery ischemia after having cannulation for venoarterial extracorporeal membrane oxygenation (VA-ECMO) have been reported rarely in literature. In this case report, female patients who are 21 years old and developed drop foot depending on ECMO during the process of lung transplantation will be presented as both to be one of the rare neurological complications connected to ECMO and its possible causes will be analyzed.

Reduced bone resorption and increased bone mineral density in women with restless legs syndrome.

OBJECTIVE: To investigate bone resorption and formation markers as well as bone mineral density in women with restless legs syndrome (RLS). METHODS: This was a prospective cross-sectional case-control study involving drug-naive women with RLS and age- and body mass index (BMI)-matched female controls. Routine blood analyses, markers of bone formation, procollagen 1 n-terminal peptide, bone resorption, c-telopeptide of type 1 collagen (CTX), sclerostin, and bone mineral density (BMD) were compared between the 2 groups. Pregnant or breastfeeding women and individuals with comorbidities other than iron deficiency, type 2 diabetes mellitus, or hypertension were excluded. RESULTS: A significant increase in lumbar BMD was found among 78 women with RLS as compared to 78 age- and BMI-matched controls (p = 0.001). The proportion of patients with osteopenia as defined by a lumbar T score was significantly lower among patients with RLS (p = 0.040). CTX and sclerostin were significantly lower in patients with RLS (p = 0.006 and p = 0.011, respectively), as were the levels of 25-hydroxy vitamin D3, calcemia, and free T3 (p = 0.017, p = 0.017, and p = 0.002, respectively). CONCLUSIONS: Despite lower 25-hydroxy vitamin D3, patients with RLS had lower bone resorption markers, higher lumbar BMD, and lower frequency of lumbar osteopenia. As patients with RLS make movements night and day to decrease the severity of their symptoms, they unconsciously perform exercise, which may potentially explain the better bone profile among patients with RLS than in controls.