Demographic and clinical characteristics of our patients diagnosed with laryngeal dystonia.

PURPOSE: Laryngeal dystonia (LD) is a focal dystonia affecting laryngeal musculature with no known etiology or cure. The present study evaluated the sociodemographic and clinical features of patients diagnosed with LD. MATERIALS AND METHODS: All patients diagnosed with LD at our University Hospital's Ear, Nose, and Throat Department between January 2017 and July 2023 were retrospectively analyzed. The study included 43 patients. RESULTS: Out of the 43 patients, 19 (44%) were male. At the time of diagnosis, the mean age of the patients was 35.1 years (ranging from 17 to 65 years). The mean elapsed time between the first symptom onset and the first diagnosis was 49.2 months (min. 4 months, max. 240 months). Of the participants, 94% had adductor-type LD. None of the patients had a family history of LD. Of the patients, 9 (20%) experienced a life-altering event or trauma just before the onset of symptoms. All patients who consumed alcohol reported symptom relief with alcohol intake. A total of 67.6% of patients stated that their symptoms were triggered by stress. All of our patients received at least one Botulinum toxin injection, with an average of 2.75 dosages per patient. CONCLUSION: The gender distribution was approximately equitable between males and females. There was a tendency for men to receive a diagnosis earlier than women following the manifestation of symptoms. A significant number of patients associate the emergence of their symptoms with a stressful event or traumatic experience. This study represents the initial investigation into the sociodemographic characteristics of patients within the Turkish population.

Real-life outcomes for oral disease-modifying treatments of relapsing-remitting multiple sclerosis patients: Adherence and adverse event profiles from Marmara University.

BACKGROUND: Disease-modifying treatments (DMT) are used to prevent future relapses and disability. High long-term adherence to treatment is important to achieve disease control. This study aims to investigate and compare adherence, adverse event (AE) profiles, and frequencies, main reasons for treatment discontinuation under Teriflunomide (TERI), Dimethyl Fumarate (DMF), and Fingolimod (FNG) for relapsing-remitting MS (RRMS) patients. This study is designed to explore patient-reported experiences in real-life settings. METHODS: Patients who were older than 18 years with a definite diagnosis of RRMS and no history of stem-cell transplantation were included. Outpatient clinic data files at the Neurology Department of Marmara University from June 2012 to June 2019 were examined retrospectively. RESULTS: One hundred and ninety MS patients were enrolled. 118 FNG, 51 DMF, 44 TERI treatment cycles were recorded. Time sincedisease onset, time since diagnosis, and treatment duration were significantly longer for FNG (p = 0.012, p = 0.004, p < 0.001). 72.8% of all the treatment cycles were continued. There was no significant difference in treatment continuity between the 3 DMT groups. The most common reasons for treatment discontinuation in order of frequency were adverse events, the progression of the disease, and the persistence of relapses. No significant difference was found for treatment discontinuation reasons. 32% of the patients reported at least one AE. 28% FNG, 49 % DMF, and 27.3% TERI using patients reported AEs. AEs were much more frequently reported for DMF (p = 0.015). The most common adverse events for each DMT were alopecia (n = 6, 13.6%) for TERI, flushing for DMF (n = 20, 39.2%), and persistent lymphopenia for FNG (n = 9, 7.6%). No severe or life-threatening AE was reported for DMF, one patient experienced pancreatitis under TERI, and 11 (9.3%) patients using FNG had to stop treatment due to serious or life-threatening AEs including cardiac adverse events, opportunistic infections, and dysplasia. DISCUSSION: Overall treatment discontinuation because of AEs is as low as 10.3% in this study. However, AEs are still the main reason for treatment drop-out.

Use of follow-on fingolimod for multiple sclerosis: Analysis of effectiveness and patient reported outcomes in a real-world clinical setting.

BACKGROUND: Follow-on disease modifying therapies (FO-DMTs) do not always require Phase III studies. There are concerns that cheaper FO-DMTs are only used to reduce healthcare costs. However, the well-being of people with MS (pwMS) should be a priority. We aimed to evaluate the efficacy, safety and treatment satisfaction of one of the FO- Fingolimod (FTY) used in Turkey with the approval of Turkish Ministry of Health. METHODS: PwMS under FTY were recruited from 13 centers and real-world data and answers of satisfaction and adherence statements of pwMS on FTY treatment were analyzed. RESULTS: Data of 239 pwMS were obtained. The duration of FTY treatment was 2.5 ± 0.8 (1-4) years in pwMS who were included in the study and whose treatment continued for at least one year. Significant decreases in annual relapse rate (p < 0.001), Expanded Disability Status Scale (p < 0.001) and neuroimaging findings (p < 0.001) were observed. While 64% of the patients were satisfied and 71.5% were found to adherent with this FO-FTY. CONCLUSION: This multicenter retrospective study found that the efficacy, safety and treatment adherence of a prescribed FO-FTY were consistent with the results of real-world studies. Studies including real-world data may provide guidance to address issues related to FO-FTY use.

Assessment of the Effect of Subthalamic Deep Brain Stimulation on Sleep Quality of Parkinson's Disease Patients.

AIM: To investigate the effects of subthalamic deep brain stimulation (STN DBS) therapy on sleep quality of Parkinson?s Disease (PD) patients and the relationship between sleep, motor symptoms, depression, and adverse effects of dopamine replacement therapies. MATERIAL AND METHODS: A total of 26 PD patients have been included and assessed using various tools both 1 week before and 8 months after the STN DBS therapy. The data collection tools were the Unified Parkinson?s Disease Rating Scale (UPDRS), Beck Depression Inventory (BDI), Montreal Cognitive Assessment (MoCA), Parkinson?s Disease Questionnaire (PDQ-39), Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS) and Polysomnography. RESULTS: PSQI, ISI, and ESS scores were found to have significantly improved after the STN DBS therapy (p=0.002, p=0.006, p < 0.001, respectively), as were the scores obtained from several PSQI sub-scales, that is, sleep duration, sleep disturbance and daytime dysfunction (p=0.023, p=0.005, p=0.032, respectively). Additionally, Wake Times After Sleep Onset (WASO) (p=0.047) and Rapid Eye Movement (REM) sleep latency values (p=0.005) were found to have decreased after the STN DBS treatment, whereas REM sleep durations (p=0,028) and REM sleep percentages (p=0.007) were found to have increased, after the STN DBS therapy. No correlation was found between the ESS scores and Levodopa Equivalent Dosage (LED) or between the scores obtained from the sleep scales and the scores obtained from the UPDRS and BDI. There was also no correlation between sleep scores and other PD-related factors. CONCLUSION: The findings of this study indicated that STN DBS therapy positively affected the PD patients? sleep. This result was attributed to the neuromodulatory effects of the STN DBS independent of the motor symptoms, depression levels, and LED decrease.

Risk assessment of obstructive sleep apnea syndrome and other sleep disorders in multiple sclerosis patients.

BACKGROUND: The aim of the present study was to determine the possible risk of OSAS in patients with MS through the STOP-BANG questionnaire, and to confirm the pre-diagnosis of OSAS by recording polysomnographic investigation in individuals with high risk. In addition, the relationship between OSAS risk and fatigue, sleepiness, depression, and disability status will be examined. METHODS: Totally 97 patients with multiple sclerosis including 36 males and 61 females with an age average of 39.92 ± 9.11 years. All participants completed the following questionnaires: STOP-Bang, Fatigue Severity Scale (FSS), Epworth sleepiness scale (ESS), Beck Depression Inventory (BDI); disability status of the participants was assessed by Expanded Disability Status Scale (EDSS). Polysomnographic sleep record was applied to the patients with high risk of OSAS according to STOP-BANG test scores. RESULTS: The STOP_BANG questionnaire revealed that 24.7% of the patients were screened as high risk for OSA. Approximately 11.3% of the patients were detected positive for OSAS based on PSG recording. Comparison of MS patients with high risk of OSA with others suggested a significant difference in terms of the age (p = 0.01). ESS positive scores were significantly correlated with positive STOP BANG outcomes (p < 0.001). ESS positive scores were negatively correlated with positive PSG outcomes. CONCLUSION: The prevalence of OSAS in MS patients based on questionnaire and PSG was found consistent with literature. Similar to the general population, increasing age was found as a risk factor for OSAS in patients with MS. STOP-BANG test may not be an adequate test to diagnose OSAS, especially in MS patients with high fatigue scores.

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.

Restless Legs Syndrome/Willis-Ekbom Disease in Multiple Sclerosis Patients with Spinal Cord Lesions.

INTRODUCTION: Spinal cord lesions in Multiple Sclerosis (MS) patients are associated with a higher risk of restless legs syndrome (RLS). In this study, we investigated the prevalence of RLS, sleep quality, presence and severity of depression, and the relationship of these parameters with cervical cord lesions in patients with RRMS. METHODS: This study was conducted in the outpatient multiple sclerosis clinic of Marmara University Hospital between October 2013 - February 2014, including 93 patients with the diagnosis of MS. After signing informed consent, demographic data, comorbidities and actual medication of the patients were collected. All patients completed the surveys including Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS) and Beck Depression Inventory (BDI). Prevalence of HBS, sleep quality and depression severity were compared between those with and without cervical cord lesions. Furthermore, the relationship between RLS and sleep quality, depression and expanded disability status scale (EDSS) was assessed. RESULTS: From overall patients, 72% were women (n=67) and 28% (n=26) were men. From all subjects, 32% (n=30) fulfilled IRLSSG diagnostic criteria. Fifty-seven percent of the patients (n=53) had pathological spinal cord lesions. Patients with RLS had significantly higher prevalence of pathological spinal cord lesions compared to patients without RLS (p=0.04). Sleep quality was found to be poor in both patients with cervical cord lesions and patients with RLS and this was statistically significant (p=0.031, p=0.0001). CONCLUSIONS: In summary, the possibility of RLS development in RRMS patients increases with the presence of lesions in spinal cord. Sleep quality was found to be poor in both patients with cervical cord lesions and patients with RLS. As RLS is a potentially treatable condition, increased awareness of diagnosis of RLS in MS patients may be important for early treatment and improve the comfort of the patient.

Multicenter study of levodopa carbidopa intestinal gel in Parkinson's disease: the Turkish experience

Background/aim: Our purpose was to determine the efficacy of levodopa carbidopa intestinal gel (LCIG) in a series of Turkish patients with Parkinson's disease (PD). Materials and methods: We had telephone calls with 54 patients from 11 neurology centers who were on LCIG treatment, and 44 patients or their caregivers were included in an eight-item survey between September 2015 and June 2016. The reliability and validity of the survey were evaluated with intraclass correlation coefficients for every question separately. Results: Average age of the patients were 63.48 and the duration of PD was 12.79 years. Average LCIG treatment period was 15.63 months. Percentages of the patients who reported they were 'better' after LCIG treatment were as follows: 80% for time spent off, 55% for dyskinesia, 65% for tremor, 85% for gait disorder, 50% for pain, 50% for sleep disorders, 42.5% for depression, 32.5% for incontinence, and 70% for activities of daily living. Cronbach's alpha was 0.795 and the intraclass correlation coefficient was reliable for the items. Conclusion: As detected by a survey performed by telephone calls with good interrater reliability, patients with PD improve with LCIG treatment in many aspects of the disease.

Acquired modification of sphingosine-1-phosphate lyase activity is not related to adrenal insufficiency.

BACKGROUND: Congenital sphingosine-1-phosphate (S1P) lyase deficiency due to biallelic mutations in SGPL1 gene has recently been described in association with primary adrenal insufficiency and steroid-resistant nephrotic syndrome. S1P lyase, on the other hand, is therapeutically inhibited by fingolimod which is an oral drug for relapsing multiple sclerosis (MS). Effects of this treatment on adrenal function has not yet been evaluated. We aimed to test adrenal function of MS patients receiving long-term fingolimod treatment. METHODS: Nineteen patients (14 women) with MS receiving oral fingolimod (Gilenya®, Novartis) therapy were included. Median age was 34.2 years (range; 21.3-44.6 years). Median duration of fingolimod treatment was 32 months (range; 6-52 months) at a dose of 0.5 mg/day. Basal and ACTH-stimulated adrenal steroid measurements were evaluated simultaneously employing LC-MS/MS based steroid panel. Basal steroid concentrations were also compared to that of sex- and age-matched healthy subjects. Cortisol and 11-deoxycortisol, 11-deoxycorticosterone and dehydroepiandrosterone were used to assess glucocorticoid, mineralocorticoid and sex steroid producing pathways, respectively. RESULTS: Basal ACTH concentrations of the patients were 20.8 pg/mL (6.8-37.8 pg/mL) (normal range; 5-65 pg/mL). There was no significant difference in the basal concentrations of cortisol, 11-deoxycortisol, 11-deoxycorticosterone and dehydroepiandrosterone between patients and controls (p = 0.11, 0.058, 0.74, 0.15; respectively). All patients showed adequate cortisol response to 250 mcg IV ACTH stimulation (243 ng/mL, range; 197-362 ng/mL). There was no significant correlation between duration of fingolimod treatment and basal or ACTH-stimulated cortisol or change in cortisol concentrations during ACTH stimulation test (p = 0.57, 0.66 and 0.21, respectively). CONCLUSION: Modification and inhibition of S1P lyase activity by the long-term therapeutic use of fingolimod is not associated with adrenal insufficiency in adult patients with MS. This suggests that S1P lyase has potentially a critical role on adrenal development rather than the function of a fully mature adrenal gland.

Deep brain stimulation as treatment for dystonic storm in pantothenate kinase-associated neurodegeneration syndrome: case report of a patient with homozygous C.628 2 T > G mutation of the PANK2 gene.

Pantothenate kinase-associated neurodegeneration (PKAN) syndrome is an autosomal-recessive neurodegenerative disease that causes progressive generalized dystonia. Currently, the disorder remains pharmacologically intractable. Herein we report the first case in which deep brain stimulation helped to relieve dystonic storm in a patient with PKAN syndrome who had homozygous c.628 2 T > G mutation of the PANK2 gene. A 10-year-old boy with PKAN disease presented with dystonic storm and was admitted to the emergency department. Examination revealed generalized dystonia and impaired breathing due to involvement of the respiratory muscles. The patient underwent surgery for bilateral globus pallidus internus deep brain stimulation. The patient showed marked response to treatment.

Clinical and cognitive profiles of patients with both Parkinson's disease and essential tremor.

Although Parkinson's disease (PD) and essential tremor (ET) are distinct clinical disorders, their coexistence can sometimes cause diagnostic problems. In this study, we conducted detailed investigations of patients with both ET and PD (ET-PD) and compared their clinical and cognitive profiles with those of patients with only ET or only PD. This study examined three groups of patients: the first group had ET-PD concomitantly (n = 9); the second group had only ET (n = 9); the third group had only PD (n = 10). The groups were compared in terms of demographic characteristics, clinical features, and cognitive functions. With the exception of positive family histories, which were more common in ET-PD than in PD patients, we found no differences among the groups with respect to demographic characteristics (p = 0.044). PD-only patients had more akinetic-rigid type Parkinsonism (p = 0.016), and their levodopa response was better than that of ET-PD patients (p = 0.017). Patients with ET-PD obtained significantly lower scores than those with pure ET on several cognitive tests, suggesting a prominent frontal-type cognitive dysfunction. In conclusion ET-PD patients differed from PD patients, showing more frequent familial tremor histories and lower levodopa responsiveness. This patient population also demonstrated more severe cognitive impairments than pure-ET patients. This result suggests that ET-PD patients are a subset of ET patients with more widespread neurodegeneration, which may indicate the presence of a syndrome that includes overlap between ET and PD.

Motor and non-motor symptoms in Turkish patients with Parkinson's disease affecting family caregiver burden and quality of life.

Parkinson's disease (PD) decreases the quality of life (QoL) of both caregivers and patients by increasing stress and burden, and it has a negative impact on their psychological state. In the present study, the authors examined the impact of PD-patient motor and non-motor clinical symptoms on the psychological health, burden, and QoL of Turkish caregivers. The study included 50 patients with PD and their caregivers. Patients' disease severity and disability, motor and non-motor symptoms, disease complications, sleep disturbances, anxiety, and depressive symptoms were assessed with various scales. Data were analyzed by multiple linear-regression models to identify variables associated with caregiver burden, psychological status, and QoL. Anxiety and depressive symptoms exhibited by the patients significantly affected the psychological state of the caregivers. Caregiver burden was increased by disease severity; the patient's degree of disability, anxiety, and depressive symptoms; and excessive daytime sleepiness. Caregiver QoL was significantly affected by the presence of dyskinesia, sialorrhea, and anxiety symptoms in patients with PD. These findings indicate that caregiving for patients with PD, particularly those in later stages, with psychiatric symptoms, affects caregiver psychological status, QoL, and caregiver burden. These results can be used to develop treatment approaches to improve caregivers' psychological status and QoL and decrease caregiver burden.

The effects of rasagiline on cognitive deficits in Parkinson's disease patients without dementia: a randomized, double-blind, placebo-controlled, multicenter study.

Cognitive impairment can occur at all stages of Parkinson's disease. Rasagiline is a selective monoamine oxidase type-B inhibitor that enhances central dopaminergic transmission. Dopamine is thought to be involved in certain cognitive processes such as working memory. We assessed the effects of rasagiline on cognitive deficits in cognitively impaired, nondemented patients with Parkinson's disease. This was a randomized, double-blind, placebo-controlled prospective study. Patients with Parkinson's disease receiving stable dopaminergic treatment were assigned to receive rasagiline 1 mg/day or placebo for 3 months. Patients were eligible if they had impairment in 2 of 4 cognitive domains (attention, executive functions, memory, visuospatial functions) in the screening neuropsychological tests, yet did not fulfill criteria for Parkinson's disease dementia. Fifty-five patients were randomized; 48 patients completed the study. Patients in the rasagiline group showed significant improvement in digit span-backward compared with the placebo group (P = .04), with trends favoring rasagiline in digit span total and digit-ordering tests. Verbal fluency total score showed a significant difference in favor of rasagiline (P = .038), with trends favoring rasagiline in semantic fluency test and Stroop spontaneous corrections. The composite cognitive domain Z scores revealed a significant difference in favor of rasagiline compared with placebo in the attentional Z score (P < .005). There were no significant differences between the 2 groups in the other cognitive tests or cognitive domain Z scores. The monoamine oxidase type-B inhibitor rasagiline may exert beneficial effects on certain aspects of attention and executive functions in nondemented patients with Parkinson's disease with cognitive impairment.

Speech-induced primary lingual dystonia: a rare focal dystonia.

Lingual dystonia, a type of focal dystonia that may be primary or secondary, is related to brain damage, neuroleptic use, neurodegenerative, metabolic, and neurodevelopmental disorders, varicella infection, and so on. However, primary lingual dystonia induced by speaking is a rare type of focal dystonia that is usually idiopathic in origin and is characterized by increased tonus of the tongue, which causes protrusion only during speaking. This report describes a 55-year-old male patient with lingual dystonia during speech. One interesting clinical feature of this case was that the speech disturbance improved while the patient vocalized a praise-like hymn in a manner that resembled singing.

Psychotic depression: a peculiar presentation for multiple sclerosis.

Multiple sclerosis (MS) is frequently associated with a number of different psychiatric syndromes. Solely psychiatric syndrome may be the first clinical presentation of multiple sclerosis. We report a patient whose first attack was psychotic depression. The present case emphasizes that psychiatric symptoms can occur at any time during the course of the disease and, moreover, may be the presenting feature.

Leukoencephalopathy with brain stem and spinal cord involvement and high lactate: a genetically proven case with distinct MRI findings.

Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a recently described disorder with autosomal recessive mode of inheritance. Lately, mutations in the DARS2 gene, which encodes mitochondrial aspartyl-tRNA synthetase, have been found as the underlying defect. We report a 19-year-old male patient with cerebellar, pyramidal and dorsal column dysfunctions and specific magnetic resonance imaging (MRI) and characteristic magnetic resonance spectroscopy (MRS) abnormalities. The patient was compound-heterozygous for two mutations in DARS2. MRI showed selective involvement of cerebral and cerebellar white matter and superior and inferior cerebellar peduncles, without contrast enhancement. The U-fibers were spared. The sensory and the pyramidal tracts were affected over their entire length. Involvement of the intraparenchymal trajectories of the trigeminal nerves and mesencephalic trigeminal tracts was demonstrated. In the spinal cord, signal abnormalities were identified in the dorsal columns and the lateral corticospinal tracts. Proton-MRS of the frontal and cerebellar white matter showed elevated lactate, reduced N-acetylaspartate, increased myoinositol and mildly elevated choline. In LBSL, distinct MRI findings should lead to the diagnosis, which can be confirmed by the analysis of the disease gene DARS2.

The clinical utility of 99mTc-HMPAO SPECT in Fahr's disease.

Fahr's disease is a rare neurodegenerative syndrome, characterized by massive symmetrical intracerebral calcifications of the basal ganglia, dentate nuclei of the cerebellum, and the adjacent parenchyma. Computerized tomography (CT) is considerably more sensitive to detect these intracranial calcifications than other imaging modalities. The clinical, CT scan, and 99(m)Tc-D,L-hexamethylpropylene amine oxime (99(m)Tc-HMPAO) brain perfusion single-photon emission computerized tomography (SPECT) findings in a 42-year-old woman with Fahr's disease are reported, and the clinical utility of 99(m)Tc-HMPAO SPECT findings in Fahr's disease is discussed in this article. In conclusion, 99(m)Tc-HMPAO brain perfusion SPECT seems to be useful in the clinical approach to Fahr's disease, and may provide more specific and clinically relevant information when compared with anatomical imaging.