Huntington's disease with comorbid myasthenia gravis: a case report.

BACKGROUND:   In the literature, several reports are describing the coexistence of Huntington's disease (HD) or myasthenia gravis (MG) with other neurodegenerative and autoimmune disorders. Herein, we report a rare case of HD in a 66-year-old male with MG. Description of the case:  The diagnosis of MG was established by acetylcholine receptor antibodies testing and compatible clinical presentation. The diagnosis of HD was based on clinical features, family history, and DNA testing. Several immunologic mechanisms have been proposed regarding the pathogenesis of HD and MG, respectively. Sharing a common autoimmune aspect could be an uncertain but potential association between the two disorders. CONCLUSION:   The probability of HD and MG occurring in the same patient is extremely small. While a number of neurological and autoimmune disorders have been reported with HD and MG, this is the first described coexistence of these two entities. HIPPOKRATIA 2019, 23(1): 28-29.

Investigation of the motor system in two siblings with Canavan's disease: a combined transcranial magnetic stimulation (TMS) - diffusion tensor imaging (DTI) study.

Canavan's disease (CD) is a hereditary leukodystrophy caused by mutations in the aspartoacylase gene (ASPA), leading to spongiform degeneration of the white matter and severe impairment of psychomotor development. We present the cases of two non-Jewish sisters with CD that have a milder and protracted clinical course compared to typical CD. MRI imaging revealed bilateral high-signal-intensity areas in the thalami and the internal capsule and MR spectroscopy showed typical findings for CD (a marked increase in N-acetylaspartate (NAA) levels). FA values of the right and left corticospinal tracts at the level of the posterior limb of the internal capsule, and the centrum semiovale were found to be significantly reduced compared to healthy controls. From a neurophysiological point of view, the peripheral motor system was normal. In contrast, cortical stimulation at maximal intensity failed to elicit facilitated or resting MEPs and silent periods (SPs) in upper and lower limbs, providing evidence for significant upper motor pathway dysfunction.

Central motor pathways in tropical spastic paraparesis: a combined transcranial magnetic stimulation and diffusion tensor imaging study.

BACKGROUND: Previous transcranial magnetic stimulation (TMS) studies in patients with tropical spastic paraparesis (TSP) have focused on central motor conduction time measurements while other TMS parameters remained unexplored. From a neuroradiological point of view, pyramidal tract involvement with magnetic resonance imaging and diffusion tensor imaging (DTI) has been rarely reported in TSP.  Accordingly, the present study investigated the mean threshold (MT) and silent period (SP) as well as DTI measurements in TSP. CASE DESCRIPTION: A 35-year-old female patient presented with a 15-year history of spastic paraparesis with minimal upper-limb involvement. Serum and cerebrospinal fluid samples were positive for HTLV-I. TMS was performed with a figure-of-eight coil (recording, abductor hallucis and first dorsal interosseous muscles). Thr was measured at 1 % steps. SPs were elicited at 5 % increments from 0 to 100 % maximum stimulus intensity (SI), and data were used to construct a stimulus/response (S/R) curve of SI vs SP. The resulting S/R curves were fitted to a Boltzmann equation and statistically compared to control data. Voxel-based DTI analysis was performed with SPM 99. Corticospinal tractography was based on diffusion tensor data. The TMS examination disclosed that MT was significantly increased (54.5 ± 6.36 % vs 41.08 ± 7.85 % in a group of 82 controls, p=0.019). The patient's SP S/R curve had significantly reduced Max values compared to 13 age-matched controls (160.4 ± 0.91 ms vs 228.36 ± 38.69 ms, p <0.001). Fractional anisotropy was decreased in a cluster of voxels corresponding to the area of the pyramidal tract (0.388 ± 0.015 vs 0.506 ± 0.02 in 20 age-matched controls, p <0.001). CONCLUSION: The described results provide novel neurophysiological and imaging evidence for central motor pathways malfunctioning in TSP. HIPPOKRATIA 2017, 21(4): 191-193.

MMSE and MoCA in Parkinson's disease and dementia with Lewy bodies: a multicenter 1-year follow-up study.

The Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) are the most commonly used scales to test cognitive impairment in Lewy body disease (LBD), but there is no consensus on which is best suited to assess cognition in clinical practice and most sensitive to cognitive decline. Retrospective cohort study of 265 LBD patients [Parkinson's disease (PD) without dementia (PDnD, N = 197), PD with dementia (PDD, N = 40), and dementia with Lewy bodies (DLB, N = 28)] from an international consortium who completed both the MMSE and MoCA at baseline and 1-year follow-up (N = 153). Percentage of relative standard deviation (RSD%) at baseline was the measure of inter-individual variance, and estimation of change (Cohen's d) over time was calculated. RSD% for the MoCA (21 %) was greater than for the MMSE (13 %) (p = 0.03) in the whole group. This difference was significant only in PDnD (11 vs. 5 %, p < 0.01), but not in PDD (30 vs. 19 %, p = 0.37) or DLB (15 vs. 14 %, p = 0.78). In contrast, the 1-year estimation of change did not differ between the two tests in any of the groups (Cohen's effect <0.20 in each group). MMSE and MoCA are equal in measuring the rate of cognitive changes over time in LBD. However, in PDnD, the MoCA is a better measure of cognitive status as it lacks both ceiling and floor effects.

The genetic background of Parkinson's disease: current progress and future prospects.

Almost two decades of genetic research in Parkinson's disease (PD) have remarkably increased our knowledge regarding the genetic basis of PD with numerous genes and genetic loci having been found to cause familial PD or affect the risk for PD. Approximately 5-10% of PD patients have monogenic forms of the disease, exhibiting a classical Mendelian type of inheritance, however, the majority PD cases are sporadic, probably caused by a combination of genetic and environmental risk factors. Nowadays, six genes, alpha synuclein, LRRK2, VPS35, Parkin, PINK1 and DJ-1, have definitely been associated with an autosomal dominant or recessive PD mode of inheritance. The advent of genome-wide association studies (GWAS) and the implementation of new technologies, like next generation sequencing (NGS) and exome sequencing has undoubtedly greatly aided the identification on novel risk variants for sporadic PD. In this review, we will summarize the current progress and future prospects in the field of PD genetics.

Self-reported autonomic symptoms in Parkinson's disease: properties of the SCOPA-AUT scale.

BACKGROUND AND AIM: Autonomic symptoms in Parkinson's disease (PD) are very common and contribute to the severity of patient's disability. We evaluated the occurrence of autonomic symptoms in Greek patients with PD utilizing the Scales for Outcomes in Parkinson's Disease-Autonomic questionnaire (SCOPA-AUT), a specific 23-item self-completed questionnaire for the assessment of autonomic dysfunction in patients with PD. SUBJECTS AND METHODS: One hundred and sixty-one PD patients and forty matched controls were enrolled in the study. Clinical assessment was performed with the Hoehn and Yahr scale. Patients completed a demographic questionnaire, the Non-Motor Symptoms Questionnaire (NMSQuest), the Parkinson's Disease Questionnaire (PDQ-39) and the SCOPA-AUT scale which was properly translated into Greek and validated for the study. RESULTS: SCOPA-AUT scale showed a good reliability profile and  correlated well with other measures for non-motor symptoms and health-related quality measures in PD patients. PD patients scored higher than controls in the total SCOPA -AUT score (mean score 11.9 versus 6.4). Patients reported problems in many items of the SCOPA-AUT, but the most common autonomic symptoms emerged in the Urinary and the Gastrointestinal domains. Especially sialorrhea, constipation, straining for defecation, incontinence and nocturia differentiated patients from controls. Furthermore, mean total SCOPA-AUT score correlated with duration and severity of the disease. CONCLUSION: Autonomic symptoms in PD are too important to remain undetected. By incorporating into everyday practice the use of suitable and reliable questionnaires, physicians will be able to adequately detect and manage these symptoms. Hippokratia 2016, 20(2):115-120.

Evaluation of non-motor symptoms in Parkinson's Disease: An underestimated necessity.

BACKGROUND AND AIM: Νon-motor symptoms in Parkinson's disease (PD) are very common and contribute to the severity of patient's disability. We evaluated the frequency of nonmotor symptoms in patients with PD and we explored the influence of disease characteristics on the presence of these symptoms. PATIENTS AND METHODS: One hundred sixty six patients and sixty six matched controls were enrolled in the study. The Non-Motor Symptoms Questionnaire (NMSQuest), a 30-item self-completed questionnaire, was used for the evaluation of nonmotor symptoms. RESULTS: Non-motor symptoms were more common in PD patients than controls. Mean ± SD NMSQuest score was 6.76 ± 4.22 in PD patients and 5.44 ± 4.45 in controls (p=0.035). The more common non-motor symptoms in PD patients were urinary urgency (54.3%), nocturia (51.8%), constipation (45.7%) and sadness (42.1%). There was a correlation between NMSQuest score and severity of the disease. CONCLUSION: Non-motor symptoms in PD are too important to remain undetected. By incorporating into every day practice the use of suitable, reliable questionnaires, we will be able to facilitate detection and management of these symptoms.

Sympathetic skin response in Parkinson's disease before and after mental stress.

OBJECTIVES: This study aims to evaluate sympathetic sudomotor activity in Parkinson's disease (PD) by means of the sympathetic skin response (SSR) and explore its possible changes due to mental stress. METHODS: Sudomotor function was evaluated using SSR in 29 patients with PD (Hoehn and Yahr stage I-IV) without any clinical evidence of autonomic dysfunction. Twenty-seven healthy matched controls were also evaluated. SSR was elicited by electrical stimulation of the right median nerve and simultaneously recorded on the palms of both hands. Arithmetic mental stress was evoked by means of the WAIS-R arithmetic subscale. Latency and amplitude of SSR were evaluated before and after arithmetic mental stress. RESULTS: The SSR was obtained in all patients and controls. There were no significant differences in its mean latency and amplitude between patients and controls. SSR parameters were significantly correlated with disease duration, UPDRS score, and disease stage. There were also significant correlations with rigidity and bradykinesia, but not with tremor. Mental stress had no effect on SSR parameters in any group. CONCLUSIONS: SSR parameters in PD without autonomic dysfunction were comparable to matched controls. Although PD patients are sensitive to mental stress, the arithmetic task had no effect on SSR parameters. Consequently, SSR as a method of evaluation of sympathetic sudomotor function is not sufficient for exploration of subclinical autonomic dysfunction in PD, but should be combined with other tests of autonomous nervous system.

Pharmacological treatment and the prospect of pharmacogenetics in Parkinson's disease.

Parkinson disease (PD) is a progressive movement disorder marked by tremor, rigidity, bradykinesia and postural instability. Levodopa (l-dopa), usually combined with a peripheral dopa decarboxylase inhibitor, has been proved to provide the best symptomatic benefit for PD. However, its long-term efficacy is limited because of motor complications and drug-induced dyskinesia. Dopamine agonists, catechol-O-methyltransferase inhibitors and monoamine oxidase-B inhibitors are anti-parkinsonian (anti-PD) drugs that have been found to further improve the potency of l-dopa and prevent the onset of motor complications. However, as PD is a progressive disorder, all the drugs used for its therapy, manifest reduced efficacy and adverse effects with time. Research on the field of pharmacogenetics has pointed out that the genetic variability of each individual determines to a large extent the inter-individual variability in response to anti-PD drugs. Clinicogenetic trials show that drug efficacy or toxicity or susceptibility to side effects are features governed by genetic principles. This article is a review of the present pharmacological treatment of PD and current pharmacogenetic data for PD.

[Immune factors or depression? Fatigue correlates in Parkinson's disease]. / Factores inmunes o depresión? La fatiga relacionada con la enfermedad de Parkinson.

INTRODUCTION: Fatigue is a frequent symptom in Parkinson disease (PD), but its pathogenesis remains obscure. Fatigue may be influenced by depression and motor disability, but immunological factors have been also implicated. The purpose of the study was to assess fatigue in PD patients in relation to depression and various immunological factors. SUBJECTS AND METHODS: Forty PD patients and 26 normal matched controls were studied. Fatigue was assessed by the Fatigue Severity Scale (FSS). The Beck Depression Inventory (BDI) was employed for depression screening. The following immunological factors were estimated: a) T- and B-lymphocytes, T-lymphocyte subsets (helper/suppressor cells) as well as natural killer cells (NK); b) circulating levels of interleukins IL-1alpha, IL-1beta, IL-6, IL-1 receptor antagonist (IL-1Ra) and tumor necrosis factor-alpha. RESULTS: FSS mean score was higher in PD patients compared to controls (p < 0.01). Significant differences between patients and controls were found in the following immunological parameters. In PD patients: a) mean percentage of NK cells was higher, p < 0.01); b) IL-1beta levels were significantly increased (p < 0.01) and IL-1Ra levels were decreased (p < 0.001). FSS correlated significantly to BDI (p < 0.008). Circulating Il-1Ra levels correlated to fatigue severity (p < 0.01), but after exclusion of depressed PD subjects this correlation significance level dropped to p = 0.055. CONCLUSIONS: Our results indicate that fatigue is a common non motor symptom in PD. Immunological differences between PD patients and controls were observed in percentages of NK cells, IL-1beta and IL-1Ra blood levels. Fatigue correlated to depression and IL-Ra levels. However after exclusion of depressed subjects IL-1Ra levels showed only a tendency to significance, leaving depression as the principle correlate of fatigue.

¿Factores inmunes o depresión? La fatiga relacionada con la enfermedad de Parkinson / Immune factors or depression? Fatigue correlates in parkinson’s disease

La fatiga es un síntoma frecuente en la enfermedad de Parkinson (EP), pero su patogénesis permanecesin aclarar. El propósito de este estudio fue evaluar la fatiga de pacientes con EP en relación con los factores inmunológicos.Sujetos y métodos. Se estudiaron 40 pacientes con EP y 26 sujetos control. La fatiga se evaluó con la Fatigue SeverityScale (FSS). Se empleó el Beck Depression Inventory (BDI) para examinar la depresión. Como factores inmunológicos se estudiaron los linfocitos T y B, subclases de linfocitos T (helper y supressor), así como las células natural killer (NK), y los nivelessanguíneos de interleucinas IL-1alfa, IL-1beta, IL-6, el antagonista del receptor de IL-1 (IL-1Ra) y el factor de necrosis tumoral alfa. Resultados. Se encontró significación estadística (p < 0,01) entre los niveles sanguíneos de IL-1Ra y la gravedad de la fatiga, pero tras excluir los pacientes con depresión y EP, el nivel de significación disminuyó a p = 0,055. Conclusiones.Se hallaron diferencias inmunológicas en los niveles sanguíneos de pacientes con EP y sujetos control en los porcentajes de células NK, IL-1beta e IL-1Ra. La fatiga correlacionaba con la depresión y los niveles de IL-1Ra. Sin embargo, tras la exclusión de los pacientes con depresión, los niveles de IL-1Ra mostraron sólo una tendencia hacia la significación, y situarona la depresión como el principal factor correlacionado con la fatiga

Fatigue is a frequent symptom in Parkinson disease (PD), but its pathogenesis remains obscure.Fatigue may be influenced by depression and motor disability, but immunological factors have been also implicated. The purpose of the study was to assess fatigue in PD patients in relation to depression and various immunological factors.Subjects and methods. Forty PD patients and 26 normal matched controls were studied. Fatigue was assessed by the Fatigue Severity Scale (FSS). The Beck Depression Inventory (BDI) was employed for depression screening. The following immunological factors were estimated: a) T-and B-lymphocytes, T-lymphocyte subset(helper/suppressor cells) as well as natural killer cells (NK); b) circulating levels of interleukins IL-1alpha, IL-1beta, IL-6, IL-1 receptor antagonist (IL-1Ra) andtumor necrosis factor-alpha. Results. FSS mean score was higher in PD patients compared to controls (p < 0.01). Significant differences between patients and controls were found in the following immunological parameters. In PD patients: a) mean percentage of NK cells was higher, p < 0.01); b) IL-1beta levels were significantly increased (p < 0.01) and IL-1Ra levels weredecreased (p < 0.001). FSS correlated significantly to BDI (p < 0.008). Circulating Il-1Ra levels correlated to fatigue severity (p < 0.01), but after exclusion of depressed PD subjects this correlation significance level dropped to p = 0.055. Conclusions.Our results indicate that fatigue is a common non motor symptom in PD. Immunological differences between PD patients and controls were observed in percentages of NK cells, IL-1beta and IL-1Ra blood levels. Fatigue correlated to depression and IL-Ra levels. However after exclusion of depressed subjects IL-1Ra levels showed only a tendency to significance, leaving depression as the principle correlate of fatigue

The G2019S LRRK2 mutation is uncommon amongst Greek patients with sporadic Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting approximately 2% of the population >60 years of age. Although, the etiology of PD is still unknown, the genetic background of the disease has been documented. Recently, a mutation in the LRRK2 gene, G2019S, was associated with 3-41% and 1-2% of familial and sporadic PD, respectively suggesting a pivotal role of LRRK2 in PD. In this report, we examine the association of the G2019S mutation with sporadic late-onset PD, in an independent cohort of Greek patients and controls.

Auditory event-related potentials in Parkinson's disease in relation to cognitive ability.

Auditory event-related potentials were evaluated in 45 nondemented patients with mild to moderate Parkinson's disease and 40 matched normal controls. All patients were neuropsychologically assessed by means of the Raven Colored Progressive Matrices, four subtests of the Wechsler Memory Scale (Digit Span Forward, Logical Memory, Visual Memory, Associate Learning), and the Wisconsin Card-sorting Test. The P300 component of the auditory event-related potentials was significantly prolonged in the patients with Parkinson's disease. Correlations between P300 latency and neuropsychological measures showed significant associations with lower performance on the Raven Colored Progressive Matrices and the Wisconsin Card-sorting Test. Our results indicate that for patients with mild to moderate Parkinson's disease subtle changes in cognitive abilities may be reflected as P300 prolongation.

Clinical features of parkinsonian patients with the alpha-synuclein (G209A) mutation.

The motor and neuropsychological abnormalities in eight Greek patients with Parkinson's disease (PD) carrying the alpha-synuclein gene mutation (G209A) were studied. These patients (five men, three women) belonged to six different families. Their symptoms started between 32-50 years of age (mean +/- SD, 39.7 +/- 7.6 years) and they had a mean disease duration of 5.4 +/- 2.1 years (range, 2-9 years) at the time of examination. Rigidity and bradykinesia predominated both at disease onset as well as in the later stages and rest tremor was relatively uncommon. Neuropsychological assessment showed that one patient was mildly demented while another had impairment in memory, visuoconstructive abilities, and executive function. Depression was present in only one patient. Our findings indicate that genetic forms of parkinsonism share common motor and cognitive characteristics with sporadic PD but raise the possibility that greater cognitive impairment and the relative rarity of tremor may be distinctive features worthy of further investigation.

Quality of life in Parkinson's disease: Greek translation and validation of the Parkinson's disease questionnaire (PDQ-39).

The Parkinson's disease questionnaire (PDQ-39) is a well-validated British scale for the assessment of health-related quality of life (HQoL) in Parkinson's disease (PD). The PDQ-39 has been translated into Greek and it was applied to 119 Greek PD patients. These patients were classified in stages according to the Hoehn and Yahr (HY) scale and their motor disability was assessed by means of the Unified Parkinson's disease rating scale (UPDRS) as well as the Schwab and England activities of daily living scale (ADL). The Beck depression inventory (BDI) was applied for the evaluation of depression. The translated version of PDQ-39, designated PDQ-39GrV, was validated as follows: (1) Cronbach's alpha coefficient and item-total Spearman's rank-order correlations were calculated in order to estimate the internal consistency of PDQ-39GrV scales. (2) Validity of the PDQ-39GrV was examined in terms of agreement with the clinical assessment parameters (stage, UPDRS. ADL and BDI scores). (3) Sixty one PD patients were re-evaluated 3-7 days later in order to check test-retest reliability. The results showed the following: (1) The PDQ-39GrV demonstrated very good internal consistency (alpha 0.71-0.94). Item-total correlations were statistically significant (r: 0.52-0.93). Test-retest measurements correlated significantly (p = 0.001). (2) Clinically obtained motor parameters correlated well with PDQ-39GrV scales influenced by physical aspects of the disease, while emotionally and socially influenced ones correlated with depression. Our findings indicate that PDQ-39 GrV is a reliable, easy to administer scale for the assessment of HQoL in Greek PD patients.

Concurrent validity of the Test of Nonverbal Intelligence in Parkinson's disease patients.

The Test of Nonverbal Intelligence (TONI-2; L. Brown, R. J. Sherbenou, & S. Johnsen, 1990) and Raven's Colored Progressive Matrices (RCPM; J. C. Raven, 1965) are defined as language-free measures of cognitive ability. The purpose of the present study was to investigate the relation between the RCPM and the TONI-2 for samples of patients with Parkinson's disease (n = 75) and controls (n = 47). A regression equation was computed to evaluate the relation of the RCPM scores to the TONI-2 quotient. Regression equation results indicate that there is a significant overlapping linear variance between the two measures in both patients and controls.

Seizures as a presenting feature of late onset metachromatic leukodystrophy.

OBJECTIVES: We describe 2 patients with epilepsy as an early manifestation of late onset metachromatic leukodystrophy (MLD). METHODS AND RESULTS: The first patient presented with epileptic seizures at the age of 34 years while neurological and cognitive abnormalities appeared later. MRI findings were compatible with leukodystrophy and low levels of arylsulphatase-A activity confirmed MLD. The second patient developed epileptic seizures and behavioral disturbances at the age of 19 years. She remained stable and seizure free for 8 years. Afterwards she developed uncontrolled epileptic seizures and status epilepticus as well as neurological and cognitive impairment. Leukodystrophy was diagnosed by MRI findings and low levels of arylsulphatase-A activity were compatible with MLD. CONCLUSION: Our 2 cases postulate that epileptic seizures may be an early and prominent manifestation of late onset MLD.