Non-motor Findings Research Articles

Evaluation of the visual system with visual evoked potential and optical coherence tomography in patients with idiopathic Parkinson's disease and withmultiple system atrophy.

In addition to motor findings, non-motor findings including alterations in visual acuity, decrease in blink reflex, and pupil reactivity cause the impaired quality of life in idiopathic Parkinson's disease (PD) and multiple system atrophy (MSA). Our study aimed to examine possible latency and amplitude changes in pattern visual evoked potentials (pVEP) along with retinal and macular changes in optical coherence tomography (OCT) in PD and MSA groups. We also intended to investigate whether any OCT parameters could be a biomarker for Parkinson's or MSA. Our study included 50 patients with PD, 15 with MSA, and 50 healthy control subjects. All patients in the study underwent neurological and ophthalmological examination and investigations of OCT to measure the retinal and macular thickness and pVEP to assess visual pathways. When PD, MSA, and control groups were compared, a significant difference was found in all retinal thickness values in average, nasal, and superior retinal nerve fiber thickness (pRNFL), and in all macular thickness values except nasal outer and inferior outer quadrants and in ganglion cell complex (GCC) thicknesses (p < 0.05). Moreover, a significant difference was found in N75, P100, and N145 latencies and N75-P100 amplitude (p < 0.05). The thickness of both pRNFL, inner and outer macular quadrants, was thinner in the MSA group than in PD but GCC thickness was thinner in PD group. The present study compared pVEP and OCT parameters in PD and MSA groups. It was concluded that pVEP and OCT examinations were of importance in that they were easily accessible, affordable, noninvasive biomarkers that might be used in early periods and progression of the disease and in follow-up.

Behavioral characterization in MPTP/p mouse model of Parkinson's disease.

We evaluated the practicability of using the rarely utilized C57BL/6N mouse as a Parkinson's disease model established via the acute MPTP/probenecid (MPTP/p) protocol. We confirmed dopaminergic degeneration in terms of decreased expression levels of tyrosine hydroxylase in the substantia nigra and striatum of MPTP/p-lesioned mice. In addition, acute MPTP/p-lesioned mice demonstrated initial motor dysfunctions followed by spontaneous recovery. Interestingly, these MPTP/p-lesioned mice exhibited anxiolytic and antidepressive behaviors upon recovery from these motor deficits. Additionally, increased expression of norepinephrine transporters in several brain regions, including the hippocampus, medial prefrontal cortex, and striatum, and an elevated rate of adult neurogenesis (in terms of increased numbers of doublecortin-positive neuroblasts) in the hippocampus were observed after recovery from motor dysfunctions. We suggest that the emotional alterations observed under these experimental conditions may be associated with enhanced adult neurogenesis, increased levels of norepinephrine transporters, and/or a possible interplay between these two factors. Consequently, this acute MPTP/p model adequately satisfies the criteria for the validity of a Parkinson's disease model regarding dopaminergic loss and motor impairment. However, the non-motor findings may offer novel evidence against the practicability of utilizing the acute MPTP/p-lesioned mice for modeling the emotional aberrations found in Parkinson's disease patients.

Amyotrophic Lateral Sclerosis Is Accompanied by Protein Derangements in the Olfactory Bulb-Tract Axis

Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by progressive muscle paralysis due to the degeneration of upper and lower motor neurons. Recent studies point out an involvement of the non-motor axis during disease progression. Despite smell impairment being considered a potential non-motor finding in ALS, the pathobiochemistry at the olfactory level remains unknown. Here, we applied an olfactory quantitative proteotyping approach to analyze the magnitude of the olfactory bulb (OB) proteostatic imbalance in ALS subjects (n = 12) with respect to controls (n = 8). Around 3% of the quantified OB proteome was differentially expressed, pinpointing aberrant protein expression involved in vesicle-mediated transport, macroautophagy, axon development and gliogenesis in ALS subjects. The overproduction of olfactory marker protein (OMP) points out an imbalance in the olfactory signal transduction in ALS. Accompanying the specific overexpression of glial fibrillary acidic protein (GFAP) and Bcl-xL in the olfactory tract (OT), a tangled disruption of signaling routes was evidenced across the OB–OT axis in ALS. In particular, the OB survival signaling dynamics clearly differ between ALS and frontotemporal lobar degeneration (FTLD), two faces of TDP-43 proteinopathy. To the best of our knowledge, this is the first report on high-throughput molecular characterization of the olfactory proteostasis in ALS.

Deep brain stimulation withdrawal syndrome: Case report

Background: In the treatment of advanced Parkinson's disease, our follow-up information about DBS treatment, which is effective on both motor and non-motor findings, is gradually increasing. In recent years, we have learned about the side effects of apathy and suicide related to the rapid discontinuation of dopaminergic treatments after DBS. As case reports, cases with DBS withdrawal syndrome with severe deterioration in motor findings after sudden discontinuation in DBS treatment and non-response to oral treatment were reported.

Parkinson's Disease Profile – A 17-Year Patient Analysis

Objective: Idiopathic Parkinson's disease (IPD) is a progressive degenerative disease, which increases over the age of 65 years and causes disability in advanced stages. The main pathology is the degeneration of the basal ganglia, especially the substantia nigra. In the clinic, motor and non-motor findings (NMF) are seen, and treatment approach is symptomatic. Factors that increase the risk in Parkinson's disease are male gender, old age, white race, environmental conditions, trauma, vascular diseases, family history, and genetic mutations. In this study, idiopathic Parkinson's patients who came to our movement disorders outpatient clinic in the last 17 years were evaluated retrospectively. We aimed to determine the IPD profile in our region through demographic and clinical findings and treatments used and compare the results with the literature. Methods: We evaluated 1150 patients admitted to the neurology department of movement disorders outpatient clinic due to parkinsonism. Five hundred seventy-eight patients with IPD were included in the study. Demographic data such as age, sex, place of birth, place of residence (rural/urban), comorbidities, family history, and habits were recorded. Results: A total of 63.5% of the patients were male. The mean age of the patients was 68.51(SD ± 10.35) years old for males and 68.37(SD ± 11.22) years old for females, 62.61(SD ± 11.31) for males and 62.55(SD ± 12.46) for females. 66.4% of the patients had the first clinical finding as tremor, while 55.4% had the tremor as the leading complaint. It was seen that 57% of the patients had NMF. It was observed that 52.8% of the patients did not have dementia. As the clinical stage progressed, it was determined that there was a significant increase in dementia rate. Hypertension (HT) (M/F%:35,2/47,2 p=0.01) and thyroid diseases (M/F%:2.3/10.3 p=0,00) were more frequent in female patients than in male patients. Impulsive-compulsive behaviors (ICBs) which are treatment-related problems were more common in males than in females (M/F%:17.8/8.5 p=0,00). Conclusion: The results were found to be similar to the literature. In this study, we have noticed the neglected, incomplete, or inadequately questioned parameters in routine-intensive outpatient conditions. Taking these results into consideration, we had the opportunity to correct our shortcomings in our future studies.

Cognitive and brain micro-structural correlates of alexithymia in essential tremor patients

Essential tremor (ET) is the most common movement disorder which has both motor and non-motor findings such as neuropsychiatic symptoms. Alexithymia is defined as inability to identify and describe emotions experienced by one's self or others. In our study, we aimed to evaluate the neurocognitive and brain micro-structural correlates of alexithymia in ET. 40 ET patients (mean age = 53.05 ± 19.74 years), were included. Fahn-Tolosa-Marin Tremor Rating Scale, Toronto Alexithymia Scale (TAS), Beck Depression Inventory, Beck Anxiety Inventory and detailed neurocognitive evaluation were applied to all patients. The patients were divided into three groups based on their TAS scores: no alexithymia, probable alexithymia, definite alexithymia. Diffusion Tensor Imaging (DTI) was performed in all patients. The mean TAS score was 50.05 ± 10.06. Depressive symptoms and anxiety levels were higher in definite alexithymia (p < 0.001, p < 0.01). Partial correlation controlling for age, gender and educational level between alexithymia scores and each cognitive test showed significant association between similarities (p < 0.001) and phonemic verbal fluency (p = 0.04). Left orbitofrontal cortex average diffusion coefficient (ADC) value (p = 0.05), left anterior cingulate cortex fractional anisotropy (FA) value (p = 0.04), right cuneus FA value (p = 0.04), left amygdala ADC value (p = 0.01) and left insula ADC value (p = 0.02) were differed between groups. TAS and DTImetrics were not found to be independently associated with the level of anxiety (p < 0.001) and depressive symptoms (p < 0.01). As a conclusion, impairments in executive function and complex attention were correlated with higher levels of alexithymia in ET. Many micro-structural alterations were determined to be correlated with alexithymia levels.

Beyond the Typical Syndrome: Understanding Non-motor Features in Niemann-Pick Type C Disease.

Niemann-Pick type C (NPC) is a rare autosomal recessive disorder characterized by storage of unesterified glycolipids and cholesterol in lysosome. NPC's clinical presentation is highly heterogeneous, depending on the time of onset. It encompasses visceral, neurological, and/or psychiatric manifestations. As the motor findings are so important and devastating in this disease, there is a lack of description about non-motor symptoms, even though they play important role in quality of life of NPC patients. We described the most common non-motor findings in NPC like cognitive dysfunction, neuroimaging, psychiatric symptoms, sleep disorders, seizures, hearing problems, respiratory and other systemic features, bladder and fecal dysfunction, hypersalivation, and malnutrition. In this review, we highlighted the importance of these undervalued symptoms and their management. Specific measures of all aforementioned clinical features may work as relevant biomarkers in order to evaluate successful therapies in future clinical trials.

Evidence of central involvement in essential tremor: a detailed study of auditory pathway physiology.

Essential tremor (ET) is a common tremor disorder that is likely neurodegenerative. The pathophysiology of ET involves the cerebellum and its connections in the brainstem and thalamus. Hearing dysfunction has been shown to be a non-motor finding in ET patients. A limited number of studies have suggested that cochlear pathology is the cause, but studies have not evaluated the integrity of the primary auditory pathway in ET. The main aim of this study is to investigate the integrity of the auditory pathway via auditory brainstem response (ABR) and auditory middle latency response (AMLR), thereby allowing us to evaluate the auditory pathway from the 8th cranial nerve to the cerebral cortex. Sixteen ET patients and sixteen age- and gender-matched controls (64 ears) were evaluated. In the ABR study, we detected prolongation of wave V peak latencies (ms) in ET (p = 0.02). In the AMLR study, P0 (p = 0.03), Pa (p = 0.008), Na (p = 0.03), and Nb (p = 0.01) waves differed between the two groups. Eleven ET patients and four control subjects had abnormal electrophysiological findings (ABR or AMLR or both) (68.8% vs. 25%, p = 0.01). Tremor duration was greater in ET patients with abnormal electrophysiological findings (p = 0.01). Finally, we observed prolongation of latencies after the ABR III wave, indicating that abnormalities exist within the superior olivary complex. For the first time, our research provides evidence that ET-related pathology is present at the subcortical and cortical levels of the auditory pathway.

Factors Predicting Falls in Parkinson’s Disease: Investigation of Motor, Non-motor Findings and Different Dual Task Activities

Factors Predicting Falls in Parkinson’s Disease: Investigation of Motor, Non-motor Findings and Different Dual Task Activities

Factors Predicting Falls in Parkinson’s Disease: Investigation of Motor, Non-motor Findings and Different Dual Task Activities

Factors Predicting Falls in Parkinson’s Disease: Investigation of Motor, Non-motor Findings and Different Dual Task Activities

Comparison of the Olfactory Bulb Volume and the Olfactory Tract Length Between Patients Diagnosed with Essential Tremor and Healthy Controls: Findings in Favor of Neurodegeneration.

PurposeEssential tremor (ET) is the most common movement disorder. In recent years, an increasing number of studies have shown that this disease also has a variety of non-motor findings and may be of a neurodegenerative nature. This study aimed to evaluate the olfactory bulb volume (OBV) and the olfactory tract length (OTL) and to demonstrate possible neurodegeneration in ET patients using magnetic resonance imaging (MRI).MethodsThe study included 30 ET patients (mean age=29.53±11.82 years) and 30 healthy controls (mean age=30.00±11.68 years). In the cranial MRI examination of both groups, the right, left and total OBV values ​​were measured in mm3 and the right and left OTL values ​​were calculated manually in mm.ResultsThere was no significant difference between the patient and control groups in the measured OBV values, but the OTL value of the patient group was statistically significantly lower than the control group.ConclusionOur study showed that the olfactory system might be involved in ET cases. We think that olfactory dysfunction, one of the non-motor symptoms in ET, can be clearly elucidated through both anatomical and functional studies, to be conducted with larger patient groups.

Relation of Apathy to Motor and Non-motor Findings in Parkinson’s Disease

Relation of Apathy to Motor and Non-motor Findings in Parkinson’s Disease

Genetic fine-mapping of the Iowan SNCA gene triplication in a patient with Parkinson\u2019s disease

The “Iowa kindred,” a large Iowan family with autosomal-dominant Parkinson’s disease, has been followed clinically since the 1920s at the Mayo Clinic. In 2003, the genetic cause was determined to be a 1.7 Mb triplication of the alpha-synuclein genomic locus. Affected individuals present with an early-onset, severe parkinsonism-dementia syndrome. Here, we present a descendant of the Iowa kindred with novel, disease-associated non-motor findings of reduced heart rate variability, complete anosmia, and a rare skin condition called colloid milium. At autopsy, key neuropathological findings were compatible with diffuse Lewy body disease. Using high-resolution comparative genomic hybridization (CGH) array analysis to fine-map the genomic breakpoints, we observed two independent recombination events of the SNCA locus that resulted in a genomic triplication of twelve genes, including SNCA, and the disruption of two genes, HERC6 and CCSER1, at the genomic breakpoints. In conclusion, we provide further evidence that the mere two-fold overexpression of alpha-synuclein leads to a fulminant alpha-synucleinopathy with rapid progression and severe clinical and neuropathological features.

Parkinsonism in elderly rheumatoid arthritis patients.

The incidences of extrapyramidal symptoms and Parkinson's disease were reported to be increased in patients with rheumatoid arthritis (RA). In this study we aimed to explore the frequency of the symptoms of Parkinsonism among RA patients older than 60 years. 30 (6 males, 24 females) consecutive RA patients, followed at a rheumatology outpatient clinic, who were 60 years of age or older; 23 patients who were diagnosed as PD and 50 sex and age matched healthy controls were included to the study. All participants were examined for the motor and non-motor findings of Parkinsonism including bradykinesia, rigidity, tremor, postural abnormality, upper limb sway abnormality, gait impairment, decrease in facial expression, seborrhea, slowing of speech and impairment in the self care. When the RA, PD cases and healthy control group were compared for bradykinesia, rigidity, tremor, posture, upper limb sway, gait impairment, facial expression, seborrhea, speech and self care; highly significant differences were seen for all parameters. Two out of the 30 RA cases (6,7%) were diagnosed as Parkinson's disease. The signs of Parkinsonism and Parkinson's disease were found more frequent in elderly RA cases as compared to healthy controls.

New triggers and non-motor findings in a family with rapid-onset dystonia-parkinsonism

BackgroundA woman from Italy presented with dystonic leg symptoms at the age of 59. Rapid-onset dystonia-parkinsonism (RDP) was not suspected until 3 affected children (2 male, 1 female) with presentations consistent with the disorder were recognized. MethodsThe mother and four of her children (3 with and 1 without dystonia) were evaluated with an extensive battery including standardized history questionnaire and rating scales. In addition, all four children had cognitive testing and three of the four children had psychiatric interviews. ResultsIn this family, a T613M mutation in the ATP1A3 gene was confirmed, the most common mutation present in patients with RDP. The proband's limb dystonia was atypical of RDP, symptoms of the others affected included dysarthria, asymmetric limb dystonia, and dysphagia more consistent with RDP. The two sons developed dystonia-parkinsonism in adolescence after consuming large amounts of alcohol. All 3 of those with psychiatric interviews reached diagnosable thresholds for mood disorder (bipolar or dysthymia) and some form of anxiety disorder. ConclusionsThe phenotype and age of onset is broader than previously reported in RDP, suggesting that it could be under-reported. Prior to this study, neuropsychologic symptoms associated with RDP were under-appreciated. Those patients who are at risk or suspected of having RDP should be cautioned to avoid excessive alcohol intake. Further study is needed to assess if the cognitive and psychiatric features are part of a broader RDP phenotype and this may have implications for future research into genetic susceptibility for psychiatric disease.

Premotor Symptoms and Early Diagnosis of Parkinson's Disease

ABSTRACTParkinson's disease is a disorder characterized by the motor findings of bradykinesia, rest tremor, cogwheel rigidity, and postural instability. As the disease progresses, most patients develop numerous nonmotor signs and symptoms, many of which play a major role in reducing quality of life. What is becoming increasingly clear is that nonmotor findings, including hyposmia, sleep disorders, autonomic abnormalities, cognitive changes, and neurobehavioral changes, often precede the motor findings.

The Spectrum of Parkinsonian Manifestations Associated With Glucocerebrosidase Mutations

Mutations in the glucocerebrosidase gene (GBA) result in Gaucher disease and can be associated with a phenotype characterized by adult-onset progressive neurologic deterioration and parkinsonism. To define the clinical and neurologic spectrum of parkinsonian manifestations associated with GBA mutations. Design, Setting, and Patients A prospective case series of 10 patients (7 men and 3 women) with parkinsonism and GBA mutations evaluated at the National Institutes of Health Clinical Center. The GBA genotypes were identified by means of DNA sequencing. Tests evaluating neurologic, motor, cognitive, ocular, and olfactory functions were performed and the results were analyzed by a single team. Genotyping identified GBA mutations N370S, L444P, and c.84dupG and recombinant alleles. The mean age at onset of parkinsonian manifestations was 49 years (range, 39-65 years), disease duration was 7.8 years (range, 1.2-16.0 years), and Unified Parkinson Disease Rating Scale part III score was 26.3 (range, 13-38). Half of the patients reported cognitive changes later in the disease course. Six patients were diagnosed as having Parkinson disease, 3 as having Lewy body dementia, and 1 as having a "Parkinson plus" syndrome. The most frequent nonmotor finding was olfactory dysfunction. Atypical manifestations included myoclonus, electroencephalographic abnormalities, and seizures. In the homozygous and heterozygous states, GBA mutations are associated with a spectrum of parkinsonian phenotypes ranging from Parkinson disease, mostly of the akinetic type, to a less common phenotype characteristic of Lewy body dementia.