Clinical course and outcome of Covid-19 in patients with myasthenia gravis.

OBJECTIVES: To analyze the prognosis and outcomes of COVID-19 in patients with MG and to determine factors associated with COVID-19 severity in patients with MG. METHODS: Information concerning COVID-19 occurrence in patients with MG was collected in this single-center observational study. Univariate and multivariate analyses were used to identify factors associated with severe Covid-19. RESULTS: Two hundred seventy-five of the 386 records of MG were included in this study. Eighty-two (29.8%) patients had concurrent COVID-19 . The patients' mean age was 50.3 ± 1.6 years, and the mean duration of MG was 6.7 ± 5.4 years. MG was diagnosed after COVID-19 in five cases. Covid-19 was mild in 45 patients (54.9%), moderate in 23 (28.1%), and severe in 14 (17.07%), while mortality occurred in four of the severe cases (4.9%). Three of the exitus patients were receiving rituximab therapy. Pre-Covid MG Activity of Daily Living (MG-ADL) severity scores were significantly high in severe cases. A history of myasthenic crisis was also higher in severe cases. Similarly, univariate and multivariate analyses revealed an association between severe COVID-19 and myasthenic crisis history and high pre-Covid MG-ADL. The type of MG treatment had no independent effect on COVID-19 severity. CONCLUSION: The vast majority of the MG patients made a good recovery from Covid-19. The risk of severe COVID-19 is high in patients with high MG-ADL severity scores and a history of myasthenic crisis.

Lack of Association between Pulse Steroid Therapy and Bone Mineral Density in Patients with Multiple Sclerosis.

Multiple sclerosis (MS) has been associated with reduced bone mineral density (BMD). The purpose of this study was to determine the possible factors affecting BMD in patients with MS. We included consecutive 155 patients with MS and 90 age- and sex-matched control subjects. Patients with MS exhibited significantly lower T-scores and Z-scores in the femoral neck and trochanter compared to the controls. Ninety-four (61%) patients had reduced bone mass in either the lumbar spine or the femoral neck; of these, 64 (41.3%) had osteopenia and 30 (19.4%) had osteoporosis. The main factors affecting BMD were disability, duration of MS, and smoking. There was a negative relationship between femoral BMD and EDSS and disease duration. No association with lumbar BMD was determined. There were no correlations between BMD at any anatomic region and cumulative corticosteroid dose. BMD is significantly lower in patients with MS than in healthy controls. Reduced BMD in MS is mainly associated with disability and duration of the disease. Short courses of high dose steroid therapy did not result in an obvious negative impact on BMD in the lumbar spine and femoral neck in patients with MS.

Basilar artery occlusion in migraine-like headache: a possible triggering effect of sumatriptan.

Headache is a common symptom at the onset of acute ischemic cerebrovascular disease. Simultaneous development of migraine-like headache and stroke in the same patient makes it difficult to differentiate between migraine-induced stroke and migraine-like headache attributed to ischemic stroke. We report a case of a 34-year-old woman with no previous migraine history who presented with migraine-like headache, thought to be a first attack of migraine, and who developed brainstem infarction shortly after triptan administration. Magnetic resonance imaging revealed an acute pontine infarction, and CT angiography revealed occlusion of the basilar artery. A detailed etiological evaluation revealed no risk factor for ischemic stroke. We believe that the migraine-like headache was the first symptom of cerebral ischemia and that sumatriptan accelerated the development of the infarction. This case report emphasizes the importance of accurate diagnosis of migraine before using triptans. Secondary causes of migraine-like headache should be excluded, especially in patients with migraine-like headache for the first time.

Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase (TIMP-1) in patients with relapsing-remitting multiple sclerosis treated with interferon beta.

OBJECTIVES: Matrix metalloproteinases (MMPs), particularly MMP-9, facilitate T-cell migration into the central nervous system. They play a key role in the disruption of the blood-brain barrier (BBB) and thus in the pathogenesis of multiple sclerosis. Interferon beta's (IFNbeta) ability to alter the balance between MMP-9 and MMP-9s natural inhibitor, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), may play a role in stabilizing the BBB. The aim of this study, was to evaluate serum MMP-9 and TIMP-1 and cerebrospinal fluid (CSF) TIMP-1 levels in patients with relapsing-remitting multiple sclerosis (RRMS) treated with IFNbeta-1a. PATIENTS AND METHODS: Blood and CSF samples from 14 patients with RRMS before and 6 months after IFNbeta therapy and 14 age and sex-matched controls were obtained. Levels of MMP-9 and TIMP-1 were measured using ELISA. RESULTS: Before treatment, patients with MS had higher levels of serum MMP-9 and a higher MMP-9/TIMP-1 ratio than the controls. Although serum levels of TIMP-1 were lower in RRMS patients than in the controls, the differences did not reach statistical significance. CSF levels of TIMP-1 were significantly lower in RRMS patients. In the sixth month of IFNbeta therapy serum MMP-9 and the MMP-9/TIMP-1 ratio were significantly decreased, whereas the changes in serum TIMP-1 were not statistically significant. There was a significant increase in CSF TIMP-1 levels in the sixth month of IFNbeta therapy. CONCLUSIONS: Our result shows that RRMS patients have an impaired MMP-9 and TIMP-1 balance, and that 6 months of IFNbeta therapy is beneficial in restoring this balance.

The efficacy and safety of dipyrone (Novalgin) tablets in the treatment of acute migraine attacks: a double-blind, cross-over, randomized, placebo-controlled, multi-center study.

Dipyrone, an effective analgesic drug, is widely used in the management of headache. However, few studies have evaluated its efficacy and safety in migraine. We aimed to assess the efficacy and safety of 1 g dipyrone (Novalgin, two 500 mg tablets) on pain and related symptoms in acute migraine attacks with or without aura in a double-blind, cross-over, randomized, placebo-controlled, multi-center study design. Seventy-three migraine with or without aura patients, diagnosed according to the IHS criteria, were randomized to receive dipyrone (for 2 attacks) and placebo (for 1 attack). Pain intensity was measured on a four-point verbal pain scale before and 1, 2, 4 and 24 hours after drug intake. Significant improvement of pain was achieved with dipyrone compared to placebo at all time points measured. Both patient and physician evaluations were significantly in favor of dipyrone. Side effects were few and trivial in both groups. We conclude that dipyrone is an effective, safe and cost-effective option in acute migraine management.

Temperament and character profiles of patients with tension-type headache and migraine.

The aim of this present study was to evaluate the temperament and character profiles of persons with tension-type headache (TTH) and migraine, and to compare the results with those of healthy controls. The study population consisted of 81 patients with TTH (60 female, 21 male) and 56 patients with migraine (34 female, 17 male) aged 18-50 years, according to the criteria of the International Headache Society with age and gender - matched healthy control subjects (54 female, 28 male). All participants were instructed to complete a self-administered 240-item temperament and character inventory (TCI) questionnaire and Beck Depression Inventory (BDI). The TCI assesses four dimensions of temperament, namely, novelty seeking (NS), harm avoidance (HA), reward dependence (RD), and persistence (P), and three dimensions of character, being self-directedness (SD), cooperativeness (C) and self-transcendence (ST). According to the TCI biosocial model, the temperament dimension HA is suggested to indicate central serotonergic turnover, which is further correlated with depressive state. It was found that mean BDI scores were significantly higher in patients with TTH and migraine than in those of the controls. The BDI scores were positively correlated with HA scores (r = 0.295, P < 0.001) and negatively correlated with SD (r = -0.386, P < 0.001) and C scores (r = -0.164, P= 0.016). Multivariate analysis showed that BDI scores had significant covariation for HA, SD and C. Despite using the BDI score as a covariate, TTH patients had higher HA scores (P = 0.01) than did the control subjects. No significant differences were found between the groups regarding main NS, RD, P, SD, C and ST scores. Based on the main results of this study, it is suggested that higher serotonergic activity related to HA scores in TTH patients and their relationship with depressive symptomatology supports the role of central serotonergic involvement in TTH.

Validity and reliability of the Turkish Migraine Disability Assessment (MIDAS) questionnaire.

OBJECTIVES: The aim of this study is to assess the comprehensibility, internal consistency, patient-physician reliability, test-retest reliability, and validity of Turkish version of Migraine Disability Assessment (MIDAS) questionnaire in patients with headache. BACKGROUND: MIDAS questionnaire has been developed by Stewart et al and shown to be reliable and valid to determine the degree of disability caused by migraine. DESIGN AND METHODS: This study was designed as a national multicenter study to demonstrate the reliability and validity of Turkish version of MIDAS questionnaire. Patients applying to 17 Neurology Clinics in Turkey were evaluated at the baseline (visit 1), week 4 (visit 2), and week 12 (visit 3) visits in terms of disease severity and comprehensibility, internal consistency, test-retest reliability, and validity of MIDAS. Since the severity of the disease has been found to change significantly at visit 2 compared to visit 1, test-retest reliability was assessed using the MIDAS scores of a subgroup of patients whose disease severity remained unchanged (up to +/-3 days difference in the number of days with headache between visits 1 and 2). RESULTS: A total of 306 patients (86.2% female, mean age: 35.0 +/- 9.8 years) were enrolled into the study. A total of 65.7%, 77.5%, 82.0% of patients reported that "they had fully understood the MIDAS questionnaire" in visits 1, 2, and 3, respectively. A highly positive correlation was found between physician and patient and the applied total MIDAS scores in all three visits (Spearman correlation coefficients were R= 0.87, 0.83, and 0.90, respectively, P <.001). Internal consistency of MIDAS was assessed using Cronbach's alpha and was found at acceptable (>0.7) or excellent (>0.8) levels in both patient and physician applied MIDAS scores, respectively. Total MIDAS score showed good test-retest reliability (R= 0.68). Both the number of days with headache and the total MIDAS scores were positively correlated at all visits with correlation coefficients between 0.47 and 0.63. There was also a moderate degree of correlation (R= 0.54) between the total MIDAS score at week 12 and the number of days with headache at visit 2 + visit 3, which quantify headache-related disability over a 3-month period similar to MIDAS questionnaire. CONCLUSION: These findings demonstrated that the Turkish translation is equivalent to the English version of MIDAS in terms of internal consistency, test-retest reliability, and validity. Physicians can reliably use the Turkish translation of the MIDAS questionnaire in defining the severity of illness and its treatment strategy when applied as a self-administered report by migraine patients themselves.

Individual risk factors for carpal tunnel syndrome: an evaluation of body mass index, wrist index and hand anthropometric measurements.

In this study we aimed to identify the role of the body mass index (BMI), wrist index and hand anthropometric measures as risk factors for carpal tunnel syndrome (CTS) in both genders. Based on clinical and electrophysiologic diagnostic criteria, 154 female and 44 male CTS patients, as well as 150 female and 44 male age-matched control subjects, were selected. BMI, wrist index, hand shape index, digit index and hand length/height ratio were compared between the CTS patients and the control subjects for each gender separately. Mean BMI was found to be a significant risk factor for CTS in both genders. The wrist index was found to be higher in female (P < 0.001) and in male (P = 0.034) CTS groups than in the respective control groups. Logistic regression analysis revealed the wrist index to be an independent risk factor in females, but not in males. Shape and digit indices were significantly higher in female CTS patients than in corresponding control subjects, and regression analysis showed the shape and digit indices to be independent risk factors for CTS. In the male CTS group, the shape and digit indices did not significantly differ from their controls. Differences in the hand length/height ratio were not statistically significant in female and male CTS patients compared to their controls and it was not found to be an independent risk factor for CTS. Our study confirmed BMI as an independent risk factor for CTS in both genders. Hand and wrist anthropometrics were found to be independent risk factors for CTS in females, but not in males.

[Temperament and character profile of patients with chronic tension-type headache]. / Kronik Gerilim Tipi Bas Agrili Hastalarda Mizaç ve Karakter Profili.

OBJECTIVE: To examine the personality profiles of patients with chronic tension-type headache (CTTH) and controls using the Temperament and Character Inventory (TCI), and to determine whether the data acquired were related to the depressive status of patients. METHOD: Forty-eight patients with CTTH and 50 age, gender and education level matched, healthy, headache-free control subjects were selected for the study. The Turkish versions of TCI and Beck Depression Inventory (BDI) were applied to all participants. In the TCI, novelty seeking (NS), harm avoidance (HA), reward dependence (RD) and persistence (P) are the 4 dimensions of temperament; self-directedness (SD), cooperativeness (C) and self-transcendence (ST) are 3 dimensions of character. RESULTS: The BDI scores were positively correlated with HA scores (r=0.486, p<0.001) and negatively correlated with SD (r=-0.412, p<0.001) and C scores (r=-0.212, p=0.016). Higher HA scores and lower SD scores were found in CTTH patients when compared to the controls. After using the adjusted TCI scores (after being partialled out for the effect of BDI scores), while similar results of higher HA scores relative to healthy controls were found, SD scores did not differ statistically between the two groups. NS, RD, P, C and ST scores did not differ significantly between the two groups, using either adjusted or unadjusted TCI scores. CONCLUSION: The study of personality suggests strong effect of depressive status on SD scores in CTTH patients. Higher HA scores in CTTH patients support the role of serotonergic involvement in the pathophysiology of CTTH.

Guillain-Barré syndrome during treatment with interferon alpha for hepatitis B.

We describe a patient who developed acute demyelinating polyneuropathy on the sixth week of interferon (IFN)alpha therapy for chronic hepatitis B (HBV) infection. A 23-year-old man with chronic HBV infection had acute onset of demyelinating polyneuropathy shortly after completing a standard 6-week course of therapy with IFNalpha 2a. Clinical findings, electrodiagnostic studies and elevated cerebrospinal fluid protein levels without cells supported the diagnosis of Guillain-Barré syndrome (GBS). Other potential causes of GBS were ruled out. It remains unknown whether IFNalpha or the HBV infection itself was the cause of GBS, but it is evident that IFNalpha could not have prevented the development of GBS in our patient. We suggest that coexistent HBV infection and IFNalpha therapy may play a role in triggering an autoimmune response to peripheral nerve myelin.

MTHFR C677T polymorphism and its relation to ischemic stroke in the Black Sea Turkish population.

The MTHFR C677T mutation has been shown to be associated with venous thrombosis. The role of this mutation in ischemic stroke is unclear. We investigated whether the MTHFR mutation is a risk factor for patients with ischemic stroke in the Black Sea Turkish population or not. We analyzed 30 patients (19 male, 11 female) [median age: 50 years (range: 28-78)] with ischemic stroke who had no known predisposition factors for stroke and 242 (182 male, 60 female) healthy controls [median age: 42 years (range: 18-65)]. Detection of the MTHFR C677T mutation was performed by using commercially available allele-specific PCR-ELISA kits. Prevalence of the MTHFR C677T genotype was 49.1% (CT, 45.8%; TT, 3.3%) in controls and 50% (CT, 43.3%; TT, 6.6%) in patients [OR: 1.03, 95% CI (0.45-2.35]). The prevalence of homozygous gene mutation for MTHFR was higher among patients with stroke than control subjects, but this difference was not statistically significant. The MTHFR gene mutation is not a risk factor for ischemic stroke formation in patients from the Black Sea region in Turkey.

Ocular myasthenia gravis associated with x-linked recessive spinal and bulbar muscular atrophy.

We describe a 34-year-old patient who was admitted with episodic diplopia, ptosis, and swallowing difficulties of 6 months duration. He also had some muscle cramps aggravated by exercise since the age of 20. Bilateral ptosis of the eyelids, normal gaze, rare fasciculations of the tongue, easy fatigability of ocular and bilateral proximal limb muscles, atrophy of the testes, and gynecomastia were found on neurologic examination. Repetitive nerve stimulation studies and jitter measurement disclosed the defect of neuromuscular junction transmission. Acetylcholine receptor binding antibody was not detected. Acetylcholine esterase inhibitors relieved these episodic symptoms. A genetic study that showed an expansion of cytosine-adenine-guanine (CAG) repeat in the first exon of the androgen receptor (AR) confirmed the diagnosis of X-linked recessive spinal and bulbar muscular atrophy (X-SBMA). Thus, this case shows a rare association of ocular myasthenia gravis with X-SBMA.

Large volume donor plasmapheresis in inherited thrombophilia implicated in arterial thrombosis.

BACKGROUND: Life-threatening complications following apheresis are rare, and include venous thrombosis. Arterial thrombosis following apheresis has not been reported. CASE REPORT: A 48 year old donor had cerebral infarction following large volume plasma donation. The outcome was fatal. He was found to be heterozygous for both methylene tetrahydrofolate reductase (MTHFR) 677C-T mutation and Prothrombin 20210G-A allele. CONCLUSION: This case suggests that large volume plasma donation may trigger arterial thrombotic events in inherited thrombophilia. Therefore, the effects of plasmapheresis on coagulation system should be studied thoroughly.

Central nervous system involvement in autoimmune polyglandular syndrome.

We present a 33 year-old man, admitted because of transient deterioration of visual acuity. Magnetic resonance imaging showed diffuse central nervous system (CNS) demyelination, which largely resolved spontaneously within 4 months. The patient fulfilled the diagnostic criteria of APS type III, having autoimmune thyroiditis and alopecia universalis. In this patient, autoimmune activation against CNS antigens is thought to be the cause of reversible CNS demyelination.

X-linked spinal and bulbar muscular atrophy without proximal atrophy.

We report on a case of genetically proven X-linked spinal and bulbar muscular atrophy (X-SBMA) with prominent distal muscle atrophy and without proximal muscle involvement. The patient was a 35-year-old man who had a history of slow progressive hand and distal leg muscle weakness and wasting for 10 years. Motor nerve conduction velocities were normal with reduced compound muscle action potential amplitudes of hand and foot muscles. Sensory action potential amplitudes were small. Needle EMG revealed a chronic partial denervation with reduced interference in hand and distal leg muscles but with normal heading in all tested proximal muscles. Genetic studied showed an expansion of CAG repeat in the first exon of the androgen receptor gene, which suggests diagnosis of X-SBMA. The importance of genetic studies in this patient with unusual clinical presentation is emphasized.

Evaluation of plasma endothelin-1 levels in patients with cerebral infarction.

Endothelin-1 (ET-1) is a vasoconstrictor peptide derived from endothelium. Many authors have shown that ischemic stroke is associated with elevated plasma ET-1 levels. Also, the present findings related to plasma ET-1 levels with clinical status, size of the infarction, location of the infarction, and prognosis of the cerebral infarction were contradictory. In this study, plasma ET-1 levels in 30 patients with cerebral infarction within 72 hours after the onset of focal neurologic deficit and at their seventh day postinfarction were measured by a microplate enzyme immunoassay. Thirty sex- and age-matched healthy subjects were accepted as a control group. The mean plasma ET-1 concentrations in patients on admission, in patients at day 7, and in control subjects were 1.93 +/- 1.79, 1.03 +/- 1.02, and 0.65 +/- 0.32 fmol/mL, respectively. The mean plasma ET-1 level of patients on admission was found to be significantly higher than in patients at day 7 and in control subjects (p < 0.05). No significant difference in ET-1 levels was observed between the patients at day 7 and control subjects. Furthermore, there was no correlation between plasma ET-1 concentration and size of infarction, location of infarction, degree of clinical neurologic deficit, or prognosis of cerebral infarction. It was concluded that plasma ET-1 levels shortly after ischemic stroke were increased, which may be associated with the acute-phase reaction of cerebral infarction and may have deleterious effects on development of neuronal injury.