The Impact of Subthalamic Deep Brain Stimulation on Apathy in Parkinson's Disease Patients.

AIM: To investigate the impact of subthalamic deep brain stimulation (STN DBS) on apathy and the possible relationship between apathy, depression, and levodopa equivalent dosage (LED) in Parkinson's Disease (PD) patients. MATERIAL AND METHODS: A total of 26 patients have been evaluated via the Unified Parkinson Disease Rating Scale (UPDRS), Beck Depression Inventory (Beck D), and Beck Anxiety Inventory (Beck A), Montreal Cognitive Assessment (MoCA), Parkinson Disease Questionnaire (PDQ-39) just before and 6 months after DBS. RESULTS: Apathy scores (AES) showed a slight decrease from 54.00 ± 10.30 to 52.69 ± 8.88 without any statistical significance (p=0.502) after DBS therapy. No correlation was detected between the post-treatment changes in apathy and UPDRS scores, Beck D, Beck A. Although the direction of the correlation between changes in AES scores and LED values was negative, the results did not reach statistical significance. CONCLUSION: STN DBS therapy does not have a negative effect on apathy in PD Patients. Despite the satisfactory motor improvement, conservative dopaminergic dose reduction after surgery seems to be the main point to prevent apathy increase in PD patients after STN DBS.

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.

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.

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.

Reversible valproate-induced choreiform movements.

Valproate is an anticonvulsive drug whose mechanism of action is based on GABAergic systems. One of the infrequent adverse effects of valproate is choreiform movements. In our study, we report a patient having head trauma history with partial and secondary generalized seizures taking 1500 mg/day valproate. During the second month of the therapy, generalized chorea was observed. Since other aetiologic causes of chorea were excluded, acutely occurring chorea in the patient was thought to be related with valproate usage because of persistence of choreiform movements for days without any fluctuation. Valproate was stopped slowly and lamotrigine was added at a dose of 400 mg/day. Within a two-month period after cessation of the valproate, choreiform movements had disappeared. We thought that the history of head trauma and another antiepileptic drug usage were the risk factors for the occurrence of valproate-induced choreiform movements.

The clinical profile of nonmotor fluctuations in Parkinson's disease patients.

OBJECTIVE: Recently described nonmotor fluctuations may cause disability in Parkinson's disease patients. These fluctuations are generally grouped as sensory, autonomic and psychiatric. The clinical spectrum and frequency of these fluctuating symptoms are not well-described. METHODS: We studied the relationship of nonmotor fluctuations with motor symptoms and determined the influence of age at disease onset, duration of disease, dosage and duration of levodopa treatment in the appearance of nonmotor fluctuations. RESULTS: Statistical analysis showed a relationship of disease-related parameters with sensory and autonomic fluctuations but psychiatric fluctuations were only found to be associated with the duration of levodopa usage. The nonmotor fluctuations included in the study were observed during "on" periods as well as "off' periods. CONCLUSION: Nonmotor fluctuations had variable presentations. Moreover, their co-appearance with different types of motor fluctuations may be linked to the effect of other neurotransmitter systems acting synchronously with dopamine. Risk factors for sensory and autonomic fluctuations in patients with Parkinson's disease were early age of disease onset, longer duration and higher dose of levodopa use. Psychiatric fluctuations were only associated with higher doses of levodopa.