The Impact of Subthalamic Deep Brain Stimulation on Restless Legs Syndrome in Parkinson's Disease.

INTRODUCTION: The study aimed at evaluating the effect of subthalamic deep brain stimulation (DBS-STN) on restless legs syndrome (RLS) in Parkinson's disease (PD) patients. MATERIALS AND METHODS: We assessed the presence of RLS before and 6 and 12 months after surgery in 36 patients. Differences between patients with RLS, without RLS, and with remission of RLS in terms of sleep measures (interview and validated questionnaires) and nonmotor symptoms (NMS). Polysomnography (PSG) was performed in 24 patients. Simple and multiple regression models were used to identify potential predictors of RLS outcome after DBS-STN. RESULTS: Before DBS-STN 14 of the 36 patients (39%) were diagnosed with RLS. DBS-STN resulted in the resolution of RLS in 43% (n = 6) and the emergence of RLS in 2 (9%) patients. During the study, 20 patients remained without RLS and the patients with unremitting RLS (n = 8) experienced alleviation of symptoms. At baseline patients with RLS had higher Non-Motor Symptoms Scale (NMSS) total and sleep domain, Unified Parkinson's Disease Rating Scale (UPDRS) part IV and lower Parkinson's Disease Sleep Scale (PDSS) scores. There were no differences between the groups without and with RLS in terms of PSG recordings. CONCLUSION: DBS-STN provided relief of symptoms in most of the patients with PD and RLS. We found that RLS was associated with worse subjective sleep quality, more severe NMS, and complications of levodopa therapy. DBS-STN may have direct impact on RLS rather than related indirectly through post-surgery change in medications.

Radiation therapy in patients with implanted deep brain stimulation.

BACKGROUND: As deep brain stimulation (DBS) and radiation therapy (RT) have become established treatments for movement disorders and malignancies respectively, patients being treated with both simultaneously are becoming more frequent. OBJECTIVES: Literature regarding the safety of RT in patients with implanted DBS is scarce, and there are no clear guidelines on how to manage them. METHODS: We present a follow-up of two Parkinson's Disease (PD) patients with DBS undergoing RT in the context of previous literature. RESULTS: No adverse events nor malfunctioning of the DBS system were observed. This was in line with previous reports. CONCLUSIONS: Since there are no clear safety guidelines for RT in DBS patients, it is important to document experience in this field. A combined approach involving multidisciplinary discussions between neurosurgeons, radiotherapists, clinical oncologists and neurologists is recommended.

Prevalence and predictors of post-stroke spasticity and its impact on daily living and quality of life.

BACKGROUND AND AIMS: The present study aimed to assess the frequency of spasticity in a single-centre cohort of stroke patients in a one-year follow-up, its predictors, and its impact on the activities of daily living (ADL) and health-related quality of life (HRQoL). MATERIAL AND METHODS: A group of 121 consecutive patients with hemiparesis (aged 73 ± 11 years) was selected for further observation, out of 381 Stroke Department patients during one year. At three follow-up assessments three, six and 12 months after stroke, muscle tone and muscle weakness were rated using Modified Ashworth Scale (MAS) and Medical Research Council (MRC); Activities of Daily Living (ADL) and Health Related Quality of Life (HRQoL) were evaluated using the Barthel Index (BI), Modified Rankin Scale (mRS) and an SF-36 questionnaire. RESULTS: Fifty five of 121 (45%) patients after three months had developed spasticity (MAS ≥ 1), and in 19 of the 121 (15%) this spasticity was severe. After one year, 33/94 (35%) patients showed spasticity, and in 19/94 (20%) it was severe. Baseline muscle weakness (MRC), stroke severity as measured by the National Institutes of Health Stroke Scale (NIHSS), and greater disability (BI), were the most significant predictors of persistent post-stroke spasticity. Patients with spasticity had worse HRQoL in terms of their physical functioning, role limitations, physical pain, and vitality. CONCLUSION: Spasticity, which affects a significant proportion of stroke survivors, was present in 35% of our patients at 12 months after stroke. It has a major impact on both ADL and HRQoL. Severe disability and muscle weakness are the most important predictors of persistent post-stroke spasticity.

The impact of subthalamic deep brain stimulation on polysomnographic sleep pattern in patients with Parkinson's disease - Preliminary report.

AIM OF THE STUDY: We present the preliminary results of the study focused on the impact of subthalamic deep brain stimulation (DBS-STN) on sleep and other non-motor symptoms (NMS). MATERIALS AND METHODS: Ten patients with advanced PD, underwent two-night polysomnography (PSG) mean 1.1 week before surgery and 6.2 months post DBS programming. NMS were assessed with a set of scales before surgery and 6 months and 12 months following DBS programming. RESULTS: Contrary to previous studies, we noted deterioration of sleep pattern in the follow-up PSG. We found a decrease in total sleep time, duration of the stage N2, with prolongation of stage N1 and wakefulness after sleep onset. We did not detect any impact of DBS-STN on subjective severity of restless legs syndrome. REM - sleep behavior disorder, however reported was not observed in any patient during PSG evaluations. We also found statistically significant correlations between severity of sleep disturbances and quality of life, as well as, between severity of motor symptoms and worse objective sleep quality. CONCLUSIONS: We found that DBS-STN improved quality of life, subjective quality of sleep and sleepiness, however, contrary to the previous studies the objective parameters of sleep worsened after the surgery.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) - A Polish family with novel SACS mutations.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare hereditary ataxia, characterized by the triad of early-onset cerebellar ataxia, peripheral sensorimotor neuropathy and lower limb spasticity. Although ARSACS is increasingly reported worldwide, we present the first Polish family with a comprehensive clinical and neuropsychological assessment, harboring two novel mutations in the SACS gene. Our results demonstrate the variability in cognitive and behavioral profiles in ARSACS, which is in line with other heredodegenerative ataxias. One should be aware of ARSACS in cases of autosomally recessive inherited ataxias without common mutations.

Long-Term Follow-Up with Video of a Patient with Deafness-Dystonia Syndrome Treated with DBS-GPi.

BACKGROUND: The prevalence of deafness-dystonia syndrome (DDS) is relatively low. To our knowledge, only 2 cases of this syndrome treated with deep brain stimulation (DBS) have been reported. OBJECTIVES: We present a patient with DDS of unknown cause, refractory to medical treatment, who has been successfully treated with DBS of the internal globus pallidus (DBS-GPi) and followed up for 4 years. METHODS: A 21-year-old male, with progressive bilateral sensorineural hearing loss since the age of 3, developed dystonic movements at the age of 12. The patient presented with progressive segmental craniocervical dystonia with jaw-opening, tongue protrusion, retrocollis and gradual overflow including upper limb dystonia. Pharmacological therapy was ineffective. At the age of 17, the patient's condition deteriorated with the risk of developing a dystonic state. RESULTS: DBS-GPi implantation resulted in a striking improvement. The Burke-Marsden-Fahn Dystonia Rating Scale (BMFDRS) score improved from 75 points before the surgery to 10 points at 3 months after DBS-GPi implantation. Neurological examination at the age of 21 showed mild dystonic movements, mainly oromandibular dystonia (BMFDRS: 15 points). The clinical phenotype of our patient was consistent with Mohr-Tranebjaerg syndrome (MTS). We performed genetic analysis of the TIMM8A gene (the only gene in which mutations are known to cause MTS), but the result was negative; however, other potentially new mutations have to be considered. CONCLUSIONS: Based on our case with the longest reported follow-up of 4 years and 2 earlier reports, we advise to consider DBS-GPi in patients with DDS with unsatisfactory effect of pharmacological treatment.

The role of neuroimaging in the diagnosis of the atypical parkinsonian syndromes in clinical practice.

Atypical parkinsonian disorders (APD) are a heterogenous group of neurodegenerative diseases such as: progressive supranuclear palsy (PSP), multiple system atrophy (MSA), cortico-basal degeneration (CBD) and dementia with Lewy bodies (DLB). In all of them core symptoms of parkinsonian syndrome are accompanied by many additional clinical features not typical for idiopathic Parkinson's disease (PD) like rapid progression, gaze palsy, apraxia, ataxia, early cognitive decline, dysautonomia and usually poor response to levodopa therapy. In the absence of reliably validated biomarkers the diagnosis is still challenging and mainly based on clinical criteria. However, robust data emerging from routine magnetic resonance imaging (MRI) as well as from many advanced MRI techniques such as: diffusion weighted imaging (DWI) and diffusion tensor imaging (DTI), magnetic resonance spectroscopy (MRS), voxel-based morphometry (VBM), susceptibility-weighted imaging (SWI) may help in differential diagnosis. The main aim of this review is to summarize briefly the most important and acknowledged radiological findings of conventional MRI due to its availability in standard clinical settings. Nevertheless, we present shortly other methods of structural (like TCS - transcranial sonography) and functional imaging (like SPECT - single photon emission computed tomography or PET - positron emission tomography) as well as some selected advanced MRI techniques and their potential future applications in supportive role in distinguishing APD.

Self-awareness of executive dysfunction in Huntington's disease: comparison with Parkinson's disease and cervical dystonia.

This study assessed self-awareness of executive deficits in patients with Huntington's disease (HD) in comparison to patients with Parkinson's disease (PD) and with cervical dystonia (CD). Eighty-nine patient-proxy pairs participated in the study (23 with HD, 25 with advanced PD, 21 with mild PD and 20 with CD). Executive function was assessed with the Stroop test and the Dysexecutive Questionnaire. Insight into executive impairment in HD is mildly affected, when compared to PD and CD.

Morbidity and severity of COVID-19 in patients with Parkinson's disease treated with amantadine - A multicenter, retrospective, observational study.

BACKGROUND: After more than 2 years of the pandemic, effective treatment for COVID-19 is still under research. In recent months, publications hypothesized amantadine's potential beneficial effect on SARS-CoV-2 infection. OBJECTIVE: To compare the groups of Parkinson's Disease (PD) patients who were administered amantadine chronically and those who did not take this medication in the context of the incidence and severity of COVID-19 infection. METHODS: An observational, retrospective, multicenter cohort study was conducted among consecutive patients with idiopathic PD. The structured questionnaires were completed during the patient's follow-up visits at the Outpatient Clinic or during hospitalization. The questionnaire included the following informations: patient's age, duration of PD, Hoehn-Yahr (H-Y) stage, comorbidities, medications, COVID-19 confirmed by reverse transcription polymerase chain reaction (RT-PCR) swab test for SARS-CoV-2 with specified symptoms and their severity (home or hospital treatment). The vaccination status was verified as well. RESULTS: Five hundred fifty-two (n = 552) patients participated in the study - 329 men (60%). The mean H-Y stage was 2.44 (range: 1-4) and the mean duration of PD was 9.6 years (range: 1-34). One hundred four subjects (19%) had confirmed COVID-19 infection. Subjects over 50 years of age had a significantly lower incidence of COVID-19 (17% vs 38%, p = 0.0001) with difference also in mean H-Y stage (2.27 vs 2.49; p = 0.011) and disease duration (8.4 vs 9.9 years, p = 0.007). There were no differences between patients with and without co-morbidities. In the whole analyzed group 219 (40%) subjects were treated with amantadine. Comparing COVID-19 positive and negative patients, amantadine was used by 48/104 (46%) and 171/448 (38%) respectively. 22% of patients on amantadine vs. 17% of patients without amantadine developed COVID-19. These differences were not significant. There were no differences in morbidity and severity of COVID-19 between amantadine users and non-users as well. CONCLUSIONS: COVID-19 was less common in older (>50) with longer duration and more advanced patients. Amantadine did not affect the risk of developing COVID-19 or the severity of infection.

Poor insight into memory impairment in patients with Huntington disease.

BACKGROUND AND PURPOSE: Patients suffering from Huntington disease (HD) have been shown to present with poor self-awareness of a variety of symptoms. The study aimed to assess the self-awareness of memory impairment in HD in comparison to advanced Parkinson disease (PD), mild PD and cervical dystonia. MATERIAL AND METHODS: Self-awareness was tested in 23 patients with HD by comparing patient and caregiver ratings in reference to clinical control groups (25 patients with advanced PD, 21 with mild PD and 20 with cervical dystonia). Self-awareness was tested using the Self Rating Scale of Memory Functions, which was administered to both the patients and the caregivers. Neuropsychological assessment addressed general cognitive status (Mini-Mental State Examination), verbal learning (Auditory Verbal Learning Test, 15-word list) and mood (Montgomery-Asberg Depression Rating Scale). RESULTS: Patients with HD significantly underestimated their memory dysfunction. Underestimation of memory deficit correlated with disease duration and disease severity in HD. CONCLUSIONS: Huntington disease patients underestimate memory dysfunction. These results add to the previous reports on poor insight in HD in other domains and suggest that anosognosia in HD, albeit usually rather mild, may be a generalized phenomenon.

A Patient with Corticobasal Syndrome and Progressive Non-Fluent Aphasia (CBS-PNFA), with Variants in ATP7B, SETX, SORL1, and FOXP1 Genes.

Our aim was to analyze the phenotypic-genetic correlations in a patient diagnosed with early onset corticobasal syndrome with progressive non-fluent aphasia (CBS-PNFA), characterized by predominant apraxia of speech, accompanied by prominent right-sided upper-limb limb-kinetic apraxia, alien limb phenomenon, synkinesis, myoclonus, mild cortical sensory loss, and right-sided hemispatial neglect. Whole-exome sequencing (WES) identified rare single heterozygous variants in ATP7B (c.3207C>A), SORL1 (c.352G>A), SETX (c.2385_2387delAAA), and FOXP1 (c.1762G>A) genes. The functional analysis revealed that the deletion in the SETX gene changed the splicing pattern, which was accompanied by lower SETX mRNA levels in the patient's fibroblasts, suggesting loss-of-function as the underlying mechanism. In addition, the patient's fibroblasts demonstrated altered mitochondrial architecture with decreased connectivity, compared to the control individuals. This is the first association of the CBS-PNFA phenotype with the most common ATP7B pathogenic variant p.H1069Q, previously linked to Wilson's disease, and early onset Parkinson's disease. This study expands the complex clinical spectrum related to variants in well-known disease genes, such as ATP7B, SORL1, SETX, and FOXP1, corroborating the hypothesis of oligogenic inheritance. To date, the FOXP1 gene has been linked exclusively to neurodevelopmental speech disorders, while our study highlights its possible relevance for adult-onset progressive apraxia of speech, which guarantees further study.

Worldwide Survey of Clinician Practice on use of Adjunctive Therapies Following Botulinum Toxin Injection for Spasticity.

OBJECTIVE: Non-pharmacological adjunctive therapies can be used alongside botulinum toxin injection to enhance its efficacy. The objective of this global study was to determine the current practice and perception among clinicians of the use of adjunctive therapies after botulinum toxin injections for the treatment of limb spasticity. METHODS: A questionnaire with 22 questions on clinical practice demographics, self-reported use and clinician opinion on barriers to the use of complementary therapies, and priorities for future research was translated into 7 languages and distributed worldwide through national and international professional associations concerning (neuro)rehabilitation. RESULTS: A total of 527 clinicians from 52 countries responded to the survey. Most commonly used physical interventions were: active exercise programmes at home (81%), stretching programmes at home (81%), and splinting (70%), followed by active movement exercises (65%) and within 30 min of botulinum toxin injection and constraint induced movement therapy (63%). The main barriers reported by clinicians to provision of these interventions were clinicians' lack of time, limited financial resources, and lack of evidence. Future research should focus primarily on immediate active movement exercises and passive stretching. CONCLUSION: Worldwide, clinicians often recommend adjunctive therapies after a botulinum toxin injection to reduce spasticity. The most commonly used physical interventions among clinicians were active exercises at home, stretching at home, and splinting. Lack of evidence, time and financial constraints were identified as barriers to providing these interventions.

Self-awareness of motor dysfunction in patients with Huntington's disease in comparison to Parkinson's disease and cervical dystonia.

Individuals suffering from Huntington's disease (HD) have been shown to present with poor self-awareness of a variety of symptoms. The aim of this study was to better assess the self-awareness of motor symptoms and activities of daily living (ADL) impairment in HD, in comparison to Parkinson's disease (PD) and cervical dystonia (CD). In particular, the anosognosia/anosodiaphoria of involuntary movements has been investigated. Self-awareness was tested in 23 patients with HD by comparing patient and caregiver ratings in reference to clinical control groups (25 PD with dyskinesias, PDdys; 21 PD without dyskinesias, PDndys; and 20 with CD). Patients were assessed neurologically by relevant rating scales. Self-awareness was tested using a scale based on 15 films demonstrating 3 types of motor symptoms (chorea/dyskinesias, parkinsonism, torticollis) as well as the Self-Assessment Parkinson's Disease Disability Scale. General cognitive status, verbal learning, cognitive control, and mood were also analyzed. Our results indicate that self-awareness of choreic movements was affected more severely in HD than in PDdys, despite comparable cognitive status. Patient-proxy agreement on ADL impairment was roughly similar in all clinical groups. The results are discussed in the context of orbitofrontal-limbic pathology as a potential trigger of anosognosia/anosodiaphoria in individuals with HD.

Assessing self-awareness of dyskinesias in Parkinson's disease through movie materials.

The aim of our study was to determine self-awareness of dyskinesias and other core motor symptoms in Parkinson's disease (PD) through the use of movie presentations. A scale based on 10 movies (five depicting dyskinesias and five showing core symptoms) and the Self-Assessment Parkinson's Disease Disability Scale were administered to 21 patients (all with a Mini-Mental State Examination - MMSE score ≥ 25). Neurological assessment included the Unified Parkinson's Disease Rating Scale and the Hoehn-Yahr and Schwab-England scales. In addition, the MMSE, Beck Depression Inventory and Stroop task were administered. Overall, patient and caregiver ratings of dyskinesias and core PD symptoms were consistent. Two patients (9%) completely denied dyskinesias, while four patients (19%) significantly underestimated their dyskinesias. Our results confirm that poor self-awareness of symptoms in PD may be selective and that denial of dyskinesias affects only a minority of patients with normal cognitive status (MMSE ≥ 25). Most patients are aware of the presence of dyskinesias. Poor self-awareness of dyskinesias is associated with longer disease duration.

Prevalence of spasticity following stroke and its impact on quality of life with emphasis on disability in activities of daily living. Systematic review.

Spasticity is characterized by a velocity-dependent increase in muscle tone related to disturbed sensory-motor control of muscle tone following upper motor neuron damage. Spasticity and its clinical implications are still poorly described. There is no consensus concerning the number of patients developing spasticity or the relationship between spasticity and motor disabilities after stroke. Surprisingly, only a few studies have addressed the prevalence of spasticity following stroke. The present paper aims to review recent studies on prevalence of spasticity, its risk factors and on quality of life with emphasis on disability in activities of daily living and to relate collected data to situation in Poland.

Cognitive and behavioral profile of Perry syndrome in two families.

OBJECTIVE: Perry syndrome (PS) is a rare neurodegenerative disorder with autosomal dominant inheritance caused by point mutations in DCTN1 and characterized by parkinsonism, hypoventilation, weight loss, and psychiatric symptoms. Even though behavioral manifestation is a main feature of PS, detailed neuropsychological assessment was not performed in this cohort. In this study, the neuropsychological profile of individuals from one Polish and one Colombian family are presented. METHODS: Detailed clinical and neuropsychological data were obtained from Polish and Colombian families. Clinical and neuropsychological examinations on the proband from the Polish family were performed 6 times over 11 years. Each of 3 individuals from the Colombian family received a clinical and neuropsychological assessment. RESULTS: The neurologic examination showed severe parkinsonism, levodopa-induced motor fluctuations, and dyskinesias in all cases. Respiratory insufficiency was observed in 2 patients and weight loss in 1 individual. Neuropsychological assessment revealed predominant deterioration of working memory and learning capacity in the Polish patient. He also demonstrated compulsive behaviors, such as excessive shopping and eating, but only in the "on" phase. In the Colombian family, attentional deficits were present in 2 out of 3 cases. Out of 4 reported cases apathy and depressed mood were present in 2 individuals. Two cases demonstrated impulsivity and one had episodes of hypomania. CONCLUSIONS: Both of these families revealed relatively similar neurologic and neuropsychological profiles. The Polish patient's behavioral and neuropsychological profile was mostly compatible with a behavioral variant of frontotemporal dementia. Of note, not only depression and apathy, but also impulsivity can occur in PS.

The impact of subthalamic deep brain stimulation on sleep and other non-motor symptoms in Parkinson's disease.

INTRODUCTION: The non-motor symptoms have a major impact on quality of life in patients with Parkinson Disease (PD). We present results of the study on the impact of subthalamic deep brain stimulation (DBS-STN) on sleep and other non-motor symptoms in PD patients. MATERIALS AND METHODS: Thirty-six patients with advanced PD were included into the study. Twenty four were evaluated with two-night polysomnography (PSG) before surgery and at 6 months after DBS programming. The whole group (n = 36) was assessed using motor, non-motor symptoms (sleep disturbances in particular) and quality of life measures (QoL), before surgery, 6 and 12 months after DBS programming. RESULTS: DBS-STN resulted in the significant deterioration of objective sleep parameters, as assessed by PSG, mostly in terms of total sleep time, sleep efficiency, duration of N1 and N2 sleep, wakefulness after sleep onset and sleep latency. At the same time, improvement in the subjective sleep measures, other non-motor symptoms (particularly fatigue, cardiovascular, gastrointestinal, and sexual symptoms) and QoL was identified. The subjective improvement of sleep, other non-motor symptoms and QoL was most prominent in the first 6 months after DBS-STN, diminished slightly (being still better than before surgery) after 12 months, in parallel to mood deterioration. CONCLUSION: DBS-STN resulted in the subjective sleep quality improvement with worsening of objective (PSG) sleep parameters after 6 months. After 12 months all sleep clinical outcome measures were still better than before surgery, albeit worse when compared to the first follow-up visit. Subjective sleep quality correlated positively with mood.

Polyneuropathy in levodopa-treated Parkinson's patients.

Recently published studies show that the prevalence of polyneuropathy (PNP) is higher in patients with Parkinson's disease (PD) than in age-matched controls. Its pathogenesis, however is a matter of controversy. The major hypothesis is the toxicity of high concentrations of homocysteine (Hcy) possibly related to levodopa (LD) therapy. The aim of the present study was to determine the prevalence of PNP, independent of other etiologies, and to determine the relationship to demographic and clinical factors in LD-treated Parkinson's patients. A total of 102 patients (51 patients with PD and 51 sex- and age-matched healthy controls) were enrolled in the study. The presence of any risk factors for PNP, ascertained from the history and laboratory tests, was an exclusion criterion. The Toronto Clinical Scoring System (TCSS) was used for clinical assessment of PNP. The objective assessment was based on electroneurography (ENG) studies in which motor nerves (peroneal and tibial nerves) as well as sensory nerves (sural and superficial peroneal nerves) were bilaterally examined. The severity of the disease was determined using the UPDRS scale (Unified Parkinson's Disease Rating Scale) and the Hoehn-Yahr (H-Y) scale. In the PD group, the clinical and neurophysiological indicators of PNP, manifested as a symmetrical and predominantly sensory axonal neuropathy, were more frequent then in the control group and observed in 43.1% vs. 13.7% and 15.7% vs. 2% of subjects respectively. The presence of PNP correlated with age and the severity of PD. Patients with PD and PNP had a higher level of Hcy as compared to PD patients without PNP, however the difference was not statistically significant. The frequency of PNP in PD patients is higher than in controls. The characteristics and discrepancy between the number of patients with clinical and ENG detected PNP may suggest the small fiber neuropathy (SFN) as the dominant form of neuropathy in PD patients.