Reflexive and voluntary saccadic eye movements as biomarker of Huntington's Disease.

INTRODUCTION: Subtle abnormalities in the preclinical stage of Huntington's Disease (HD) can be detected using saccadic eye movement assessment reflecting disease progression. This study was aimed to evaluate abnormalities in saccade parameters in asymptomatic carriers and symptomatic HD patients at various stages of HD. MATERIAL AND METHODS: The study enrolled 104 participants, including 14 asymptomatic carriers of HTT mutations, 44 symptomatic HD patients, and 46 control subjects. HD severity was measured using the Unified Huntington's Disease Rating Scale Total Motor Score (UHDRS-TMS) and Total Functional Capacity Scale (TFC). The evaluation of rapid eye movements (reflexive saccades, anti-saccades, memory-guided saccades) was carried out using 'Saccadometer Research'. RESULTS: Measures of reflexive and volitional saccades did not differ between the asymptomatic carriers and controls. Significant latency prolongation and increased physiological variability of latency times, as well as higher error rates among HD patients, were found in all saccade tasks (p < 0.001) compared to the controls. Abnormalities in saccade parameters were more pronounced in the advanced stages of the disease. Latency of saccades and error rate of volitional saccades correlated with the UHDRS-TMS and TFC scores. CONCLUSIONS: The saccade parameters in asymptomatic HD carriers with a long time to disease development were similar to those in the control group. Saccade abnormalities appeared in symptomatic patients at the beginning of the disease, and correlated with HD severity.

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.

Mitochondrial DNA levels in Huntington disease leukocytes and dermal fibroblasts.

Huntington disease (HD) is an inherited neurodegenerative disorder caused by mutations in the huntingtin gene. Involvement of mitochondrial dysfunctions in, and especially influence of the level of mitochondrial DNA (mtDNA) on, development of this disease is unclear. Here, samples of blood from 84 HD patients and 79 controls, and dermal fibroblasts from 10 HD patients and 9 controls were analysed for mtDNA levels. Although the type of mitochondrial haplogroup had no influence on the mtDNA level, and there was no correlation between mtDNA level in leukocytes in HD patients and various parameters of HD severity, some considerable differences between HD patients and controls were identified. The average mtDNA/nDNA relative copy number was significantly higher in leukocytes, but lower in fibroblasts, of symptomatic HD patients relative to the control group. Moreover, HD women displayed higher mtDNA levels in leukocytes than HD men. Because this is the largest population analysed to date, these results might contribute to explanation of discrepancies between previously published studies concerning levels of mtDNA in cells of HD patients. We suggest that the size of the investigated population and type of cells from which DNA is isolated could significantly affect results of mtDNA copy number estimation in HD. Hence, these parameters should be taken into consideration in studies on mtDNA in HD, and perhaps also in other diseases where mitochondrial dysfunction occurs.

Pharmacokinetics of levodopa in patients with Parkinson disease and motor fluctuations depending on the presence of Helicobacter pylori infection.

BACKGROUND: According to recent investigations, the eradication of Helicobacter pylori (H. pylori) may influence levodopa (LD) pharmacokinetics (PK) and improve the motor function of infected patients with Parkinson disease (PD). The aim of this study was to compare PK of LD and its metabolite 3-O-methyldopa (3-OMD), between H. pylori-positive (HP+) and -negative (HP-) patients with PD and motor fluctuations. MATERIALS AND METHODS: Patients with the clinical diagnosis of PD, under stable LD therapy, reporting daily motor fluctuations and who had no history of previous eradication treatment were screened for the H. pylori infection with an antigen stool test. Two groups of patients-bacteria-infected and noninfected-matched demographically and clinically, were selected for the examination of PK values. Blood samples were collected after morning oral LD dose. Noncompartmental PK parameters were computed from the LD and 3-OMD plasma concentration-time data. RESULTS: Interindividual variability was seen in LD absorption curve in both groups. There were no clinically significant differences in PK parameters of LD and 3-OMD. Changes of small magnitude but with possible clinical impact were found according to tmax and Cmax that tended to be lower in HP- patients and AUC0-t that was larger in the HP+ group. The Cmax value of 3-OMD was almost identical in both groups. The HP- group had smaller AUC0-∞t of 3-OMD. CONCLUSIONS: The H. pylori infection in PD patients with motor fluctuations, despite not significantly influencing PK parameters of LD and 3-OMD, may still have important clinical implications.

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.

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.

Huntington's disease from the patient, caregiver and physician's perspectives: three sides of the same coin?

The aim of this study was to identify determinants of functional disability, patient's quality of life (QoL) and caregivers' burden in Huntington's disease (HD). Eighty HD patients participated in the study. Motor and behavioral disturbances as well as cognitive impairment were assessed using motor, behavioral and cognitive parts of the Unified Huntington Disease Rating Scale (UHDRS); Hamilton Depression Rating Scale was used to assess depression. Disability, health-related QoL and the impact of the disease on the caregivers were assessed using the following methods: UHDRS Functional Assessment Score, SF-36 Scale and Caregiver Burden Inventory. Multiple regression analysis showed that motor disturbances, cognitive impairment, apathy and disease duration were the independent predictors of disability. Depression and cognitive disturbances were the determinants of patient's QoL, while motor disturbances and depression were the predictors of the caregiver burden. Patient's disability and QoL as well as caregivers' burden should be taken into consideration while planning treatment strategy and the results of the present study show that the predictors of those treatment targets are different.

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.

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.

Self-awareness of memory function in Parkinson's disease in relation to mood and symptom severity.

OBJECTIVES: In clinical practice, discrepancies are observed between self and proxy reports of various aspects of Parkinson's disease (PD). This study aimed at assessing self-awareness of memory function in PD both by comparing patients' and caregivers' questionnaire ratings of the patients' memory and by correlating subjective ratings with verbal learning results. METHOD: Forty-five patient-proxy pairs participated in the study. Self-Rating Scale of Memory Functions was used as a questionnaire subjective measure. Auditory Verbal Learning Test (AVLT) was applied to assess verbal memory, Stroop test to assess cognitive control and Mini-Mental State Examination (MMSE) for global cognitive assessment. RESULTS: Patient self-reports did not diverge appreciably from proxy reports when global scores were considered, but patient-proxy consistency was low for individual items with the exception of those referring to verbal recall. Both patient and proxy ratings were moderately correlated with the objective measures. Patient-proxy discrepancies were associated with lower verbal learning, poor cognitive control and more severe PD symptomatology. Moreover, depression was associated with patients' overestimation of symptoms. CONCLUSION: Self-awareness of memory function is relatively well preserved in PD, but is negatively affected by depressive symptoms. Patient-proxy discrepancies increase also with disease severity, degree of memory problems and cognitive control deficits. Caregivers seem to be unaware of the specificity of memory problems in PD and report only some of them, mainly those related to verbal recall.

Psychogenic axial myoclonus: report on two cases.

Axial myoclonus (AM) is characterized by sudden muscle jerks involving axial and proximal muscles. It includes propriospinal myoclonus (PSM) which consists of trunk flexion or extension jerking with activity arising in axial muscles and spreading to caudal and rostral muscles at low velocity along propriospinal pathways. We report on two patients displaying flexion AM jerks in the absence of structural lesion of the central nervous system or electrophysiological evidence of organic origin. A conversion disorder was diagnosed. The jerks disappeared after psychoeducation with the patients remaining symptom free in 6-year long follow-up. The diagnoses of psychogenic axial (propriospinal-like) myoclonus were established. The literature on psychogenic axial (propriospinal-like myoclonus) is limited to a case report. Our cases demonstrate a good response to psychotropic medication and psychoeducation and fulfill the psychogenic movement disorder criteria. The phenomenology of psychogenic abnormal movements is diverse and PSM-like clinical picture may be a novel presentation.

[Abdominal dystonia in a patient with schizophrenia: a case report]. / Dystonia miesni brzucha u pacjentki cierpiacej na schizofrenie: opis przypadku.

The case of 31-year-old woman suffering from schizophrenia with movement disorder is described. The patient had a 7-year history of schizophrenia. In course of the psychiatric treatment the patient presented dystonic movements within abdominal muscles. The dystonic movements were of mixed character, including voluntary and involuntary ones what might have suggested their psychogenic origin. Subsequent to the exclusion of the neurological origin of the movement disorder and poor response to antipsychotic treatment, clozapine was introduced resulting in full remission of positive symptoms and functional improvement with a diminished intensity of the involuntary movements. Psychogenic movement disorders are uncommon in schizophrenic patients. Movement disorders may occur as an adverse reaction to antipsychotic treatment, especially with typical ones. However, the abdominal muscles dystonia is an uncommon manifestation of dystonia of idiopathic, drug-induced or psychogenic origin. In such cases, a liaison between the neurologist and psychiatrist is advocated and the therapeutic process using antipsychotic treatment is necessary.