Gender differences in motor and non-motor symptoms in early Parkinson disease.

ABSTRACT: Gender differences in motor and non-motor symptoms in Parkinson disease (PD) are still controversial. This study aimed to investigate gender differences in clinical characteristics in patients with early PD.This study included 415 PD patients (201 men and 214 women) with modified Hoehn-Yahr stage 1 to 3 and a disease duration of ≤5 years. Demographic information was obtained by interviews, and motor and non-motor PD symptoms were evaluated with appropriate scales.Women with PD had a shorter duration of formal education than men with PD. No significant differences were found in other demographic variables. Women with PD had significantly lower scores in Unified Parkinson Disease Rating Scale part III and postural tremor compared to men with PD, which was significant after controlling for formal education. No significant gender-related differences were found in scores related to other motor symptoms. Concerning non-motor symptoms, men with PD had higher scores of sexual function on the Non-Motor Symptoms Scale, which means sexual dysfunction was more severe or occurred more frequently in men with PD. Women with PD had significantly higher scores of sleep disturbance in the Pittsburgh Sleep Quality Index, which was not significant after adjustment for multiple comparison.The present study suggests that women with PD had milder motor symptoms compared to men with PD, and gender differences in sexual function can be observed as non-motor symptoms.

A French survey on the lockdown consequences of COVID-19 pandemic in Parkinson's disease. The ERCOPARK study.

BACKGROUND: In 2020 the coronavirus disease 19 (COVID-19) pandemic imposed a total and sudden lockdown. We aimed to investigate the consequences of the first COVID-19 lockdown (mid-March - mid-April 2020) on motor and non-motor symptoms (NMS) in a cohort of French people with Parkinson's disease (PwP). METHODS: PwP were enrolled either by an on-line survey sent from the national France Parkinson association (FP) to reach the French community of PwP or as part of outpatients' telemedicine visits followed by an hospital-based Parkinson Expert Center (PEC). All patients were evaluated using the same standardized questionnaire assessing motor and NMS (including a list of most disabling, new or worsened symptoms and Patient's Global Impression-Improvement scales [PGI-I]) psycho-social queries and quality of life. RESULTS: 2653 PwP were included: 441 (16.6%) in the PEC group and 2122 (83.4%) in the community-based group. Physiotherapy was interrupted among 88.6% of the patients. 40.9% referred a clinical modification of their symptoms. Based on the questionnaire, pain (9.3%), rigidity (9.1%) and tremor (8.5%) were the three most frequently new or worsened reported symptoms. Based on the PGI-I, the motor symptoms were the most affected domain, followed by pain and psychic state. PwP in community-based group tended to have more frequent worsening for motor symptoms, motor complications, pain and confusion than those of the PEC group. CONCLUSIONS: The first COVID-19 lockdown had a negative impact on motor and NMS of PwP. Efforts should be allocated to avoid interruption of care, including physiotherapy and physical activities and implement telemedicine. .

Demographic characteristics and delayed neurological sequelae risk factors in carbon monoxide poisoning.

AIM: Carbon monoxide (CO) is a colorless, odorless gas and tasteless. CO poisoning (COP) is one of the most frequently encountered inhalation poisonings. The most common cause of morbidity in COP is delayed neurological sequelae (DNS). DNS is the occurrence of neuropsychiatric findings within 2-240 days after discharge of patients with COP and there are no definitive diagnostic criteria. The aim of our study is; to determine the risk factors and incidence of DNS. METHOD: Our study is a retrospective, observational study. Patients with the diagnosis of COP in the emergency department between 2015 and 2016 were included in the study. Patients age, gender, findings in the initial physical examination (PE) and neurological examination (NE), blood carboxyhemoglobin (COHb) level, relation between hyperbaric oxygen (HBO) treatment and DNS were assessed. RESULTS: Total of 72 patients were included in the study. Mean age was 33.43 ±â€¯20.89. It was determined that pathological findings in the initial NE are a significant predictive factor for DNS (Odds ratio 18.600, p:0.004). Significant relation between NE and HBO treatment was present (p:00.1). There was no statistically significant relationship between initial COHb level and receiving HBO treatment (p:0.9). Median COHb level of patients with DNS was 30 (min:10, max: 43), median COHb level of patients without DNS was 25 (min:10, max:44) and there was no statistically significant relationship between the two groups according to COHb levels (p:0.7). CONCLUSION: Pathological findings in the initial neurological examination had a predictive value for delayed neurological sequelae in patients with carbon monoxide poisoning.

Motor asymmetry over time in Parkinson's disease.

BACKGROUND: Motor symptoms in Parkinson's disease (PD) patients are usually asymmetric at onset. The literature on change in asymmetry over time has mixed results, with some studies suggesting a retained asymmetry and others suggesting a progression towards symmetry. The aim of this study was to assess change in asymmetry over time. METHODS: Charts of 109 consecutive patients who had been followed in a movement disorders clinic for routine PD care were retrospectively reviewed. All patients had been treated for PD symptoms and had been seen during at least 2 annual time points over 5 years. Interval absolute differences in Unified PD rating scale (UPDRS) scores for bradykinesia, rigidity, and tremor between the right and left sides were calculated for annual time points. RESULTS: Neither bradykinesia, rigidity, nor tremor became more symmetric over a 5-year period; there was not a statistically significant change in asymmetry at any annual time point for these motor symptoms. CONCLUSIONS: The lack of observed change in UPDRS score difference suggests that motor symptoms in PD patients remain asymmetric. This is important to consider clinically when predicting the natural course of PD and considering alternative diagnoses to PD. These results may also be important in developing hypotheses for disease progression.

Impaired topographic organization in cognitively unimpaired drug-naïve patients with rigidity-dominant Parkinson's disease.

BACKGROUND: Resting-state functional magnetic resonance imaging (fMRI) and graph theory approaches have been combined to investigate the topographic organization in Parkinson's disease (PD). METHOD: Twenty cognitively unimpaired drug-naïve patients with rigidity-dominant PD (PDAR) and 20 age-, sex-, and education-matched healthy controls were included. Small-world profile and topographic properties (clustering coefficient (Cp), characteristic path length (Lp), local efficiency (Eloc), global efficiency (Eglob), nodal efficiency (Enod), nodal degree (NDeg), and nodal betweenness (NBet)) were measured and compared between two groups, with age, gender and education as covariates. Correlation analyses between topographic features and the unified PD rating scale part-III (UPDRS-III) scores, cognitive scores were performed. RESULTS: PDAR patients presented the small-world property, and abnormalities at the nodal level (Enod, NDeg, and NBet) but not at the global level (Cp, Lp, Eloc, and Eglob). Our results revealed lower nodal centralities mainly in the occipital lobe and areas of the limbic system (including amygdala nucleus), and higher nodal centralities in distributed frontal and temporal regions. Notably, the decreased nodal efficiency of occipital regions (including the calcarine area, lingual area and superior occipital gyrus (SOG)) was negatively correlated with UPDRS-III scores. And the nodal efficiency of the calcarine area was positively correlated with visuospatial scores. CONCLUSION: Our results may provide insights into the underlying pathophysiology of PDAR and aid the development of potential biomarkers of the disease progression and cognitive decline in PDAR patients.

Axial rigidity is related to the risk of falls in patients with Parkinson's disease.

BACKGROUND: Rigidity is a cardinal symptom of Parkinson's disease (PD) and is often clinically assessed by passively flexing and extending a patient's limb. Objective measurements had been employed to examine rigidity in PD subjects, including wrist, elbow or knee. OBJECTIVE: This study aimed to investigate the relationship between an objective measurement of trunk rigidity and risk of falls in patients with mild to moderate PD. METHODS: An isokinetic dynamometer Biodex System 3 was employed to assess trunk rigidity in 36 patients with mild to moderate PD at a University Department in a cross-sectional study. Risk of falls was measured by the Get Up & Go test (GU&G). Disease severity (Hoehn and Yahr staging score and the Unified Parkinson's Disease Rating Scale III), disease duration and functional status (Schwab & England activities of daily living scale) were also evaluated. RESULTS: Significant correlations between trunk extensors rigidity at 45°/s and 60°/s and risk of falls were obtained. A correlation between trunk extensors tone at 30°/s and the GU&G test almost reached significant almost reached statistical significance (r = 0.306; p = 0,066). Significant correlations between trunk flexors-extensors tone and clinical status, disease duration and functional status at 30°/s, 45°/s and 60°/s were also obtained. CONCLUSION: The results from this study suggest that the axial rigidity is related to the risk of falls in patients with mild to moderate PD. Further studies are needed with quantitative devices for axial rigidity assessment to determine the relationship between trunk rigidity in PD patients with higher disease severity and risk of falls.

Glycine receptor antibodies in PERM and related syndromes: characteristics, clinical features and outcomes.

The clinical associations of glycine receptor antibodies have not yet been described fully. We identified prospectively 52 antibody-positive patients and collated their clinical features, investigations and immunotherapy responses. Serum glycine receptor antibody endpoint titres ranged from 1:20 to 1:60 000. In 11 paired samples, serum levels were higher than (n = 10) or equal to (n = 1) cerebrospinal fluid levels; there was intrathecal synthesis of glycine receptor antibodies in each of the six pairs available for detailed study. Four patients also had high glutamic acid decarboxylase antibodies (>1000 U/ml), and one had high voltage-gated potassium channel-complex antibody (2442 pM). Seven patients with very low titres (<1:50) and unknown or alternative diagnoses were excluded from further study. Three of the remaining 45 patients had newly-identified thymomas and one had a lymphoma. Thirty-three patients were classified as progressive encephalomyelitis with rigidity and myoclonus, and two as stiff person syndrome; five had a limbic encephalitis or epileptic encephalopathy, two had brainstem features mainly, two had demyelinating optic neuropathies and one had an unclear diagnosis. Four patients (9%) died during the acute disease, but most showed marked improvement with immunotherapies. At most recent follow-up, (2-7 years, median 3 years, since first antibody detection), the median modified Rankin scale scores (excluding the four deaths) decreased from 5 at maximal severity to 1 (P < 0.0001), but relapses have occurred in five patients and a proportion are on reducing steroids or other maintenance immunotherapies as well as symptomatic treatments. The glycine receptor antibodies activated complement on glycine receptor-transfected human embryonic kidney cells at room temperature, and caused internalization and lysosomal degradation of the glycine receptors at 37°C. Immunoglobulin G antibodies bound to rodent spinal cord and brainstem co-localizing with monoclonal antibodies to glycine receptor-α1. Ten glycine receptor antibody positive samples were also identified in a retrospective cohort of 56 patients with stiff person syndrome and related syndromes. Glycine receptor antibodies are strongly associated with spinal and brainstem disorders, and the majority of patients have progressive encephalomyelitis with rigidity and myoclonus. The antibodies demonstrate in vitro evidence of pathogenicity and the patients respond well to immunotherapies, contrasting with earlier studies of this syndrome, which indicated a poor prognosis. The presence of glycine receptor antibodies should help to identify a disease that responds to immunotherapies, but these treatments may need to be sustained, relapses can occur and maintenance immunosuppression may be required.

Paliperidone palmitate versus oral risperidone and risperidone long-acting injection in patients with recently diagnosed schizophrenia: a tolerability and efficacy comparison.

Early in the course of illness, patients with schizophrenia may be particularly susceptible to adverse events (AEs). In this post-hoc, subgroup analysis of a 13-week, double-blind, double-dummy, multicenter study, patients recently diagnosed with schizophrenia (≤ 5 years) were administered once-monthly flexible-dose paliperidone palmitate (PP) (n=161; initiation doses, 150 mg eq day 1 and 100 mg eq day 8) [PP doses can be expressed as milligram equivalents (mg eq) of paliperidone or as milligrams (mg) of PP. 150 mg eq paliperidone=234 mg PP; 100 mg eq paliperidone=156 mg PP. In the USA, dosing tends to be expressed in mg] or oral risperidone [during initiation of risperidone long-acting injection (RLAI) days 1-28] and biweekly flexible-dose RLAI (n=173; initial injection day 8). Assessments were performed at baseline and days 4, 15, 22, 36, 64, and 92. Because of RLAI's release profile, data through day 22 correspond to oral risperidone in the RLAI arm. During this period, the AE profile and onset of efficacy of PP and oral risperidone were similar. The overall AE rates at week 13 for PP and RLAI were 54.7 and 50.3%, respectively, for any AE; 11.2 and 8.1% for extrapyramidal symptom-related AEs; and 2.5 and 2.3% for prolactin-related AEs. No significant differences in the mean weight change, most metabolic parameters, or mean efficacy measures were observed at end point. In patients with recently diagnosed schizophrenia, the tolerability and efficacy of PP and RLAI were generally similar over 13 weeks.

Cognitive impairment in early-stage non-demented Parkinson's disease patients.

OBJECTIVES: In Parkinson's disease (PD), Parkinson's disease dementia (PDD) and Parkinson's disease-mild cognitive impairment (PD-MCI) are common. PD-MCI is a risk factor for developing PDD. Knowledge of cognition in early-stages PD is essential in understanding and predicting the dementia process. MATERIALS AND METHODS: We describe the cognitive profile in early-stage PD patients with no prior clinical suspicion of cognitive impairment, depression or psychiatric disturbances, and investigate possible features distinguishing patients with cognitive deficits, defining a PD-MCI risk-profile. Single Photon Emission Computerized Tomography (SPECT) DaT-scan and neurological examination confirmed the diagnosis. Mini-mental state examination-, Addenbrooke's Cognitive Examination, Unified Parkinson's Disease Rating Scale scoring, Hoehn &Yahr/Activity of Daily Living staging and a neuropsychological test battery were applied. Mild cognitive impairment patients were identified according to modified criteria by Troster necessarily omitting subjective cognitive complaints. 80 patients, mean age 61.0 years (SD 6.6), mean duration of disease 3.4 years (SD 1.2) were included. 76 patients were neuropsychologically tested. RESULTS: 26 (34%) patients fulfilled modified PD-MCI criteria, 18 (69%) of these showed episodic memory deficits, 14 (54%) executive dysfunction, 13 (50%) language/praxis deficits, 12 (46%) visuospatial/constructional deficits and 9 (35%) attention/working memory deficits. Cognitive impairment was associated with higher Unified Parkinson's Disease Rating scale (UPDRS)-, bradykinesia- and rigidity scores and more symmetric distribution of symptoms, but not tremor scores. Patients with cognitive impairment were less educated. Other demographic and clinical variables were comparable. CONCLUSIONS: 34% of early-stage PD patients without prior clinical suspicion of cognitive impairment exhibit cognitive impairment, which is associated to disease severity, especially bradykinesia, rigidity, axial symptoms and less asymmetry of motor symptoms, even at early disease stages and when cognitive symptoms are mild.

Frequency and clinical correlates of retrocollis in Parkinson's disease.

PURPOSE: To investigate the incidence of retrocollis and to determine its clinical correlates in patients with idiopathic Parkinson's disease (PD). METHODS: Seventy-four patients with PD at Hoehn and Yahr stage 5 were examined for abnormal neck postures and were classified according to neck posture. Differences in age, age at PD onset, disease duration, years from PD onset to Hoehn and Yahr stage 5, cognitive state, the levodopa equivalent dose (LED) for dopaminergic drugs, and rigidity of the neck and upper and lower extremities were examined to determine the clinical correlates of abnormal neck posture. We also evaluated retrocollis in 356 patients with PD at Hoehn and Yahr stage 1, 2, 3, and 4 and 65 age matched normal controls. RESULTS: Of the 74 patients with PD at Hoehn and Yahr stage 5 examined, 21 (28.4%) had retrocollis, 3 (4.1%) had antecollis, and 1 (1.4%) had antecollis and torticollis. Whereas, only one patient had retrocollis in PD patients at Hoehn and Yahr stage 4 and under. Patients with antecollis were significantly younger than those with normal neck posture and retrocollis. There were no differences in age at PD onset, disease duration, sex, years from PD motor symptom onset to Hoehn and Yahr stage 5, cognitive state, or LED between patients with and without abnormal neck postures. Neck rigidity scores were significantly higher in patients with retrocollis and antecollis than in those with normal neck posture. CONCLUSIONS: Retrocollis is not rare in patients with PD at Hoehn and Yahr stage 5, and the incidence appeared to increase as axial rigidity increased.

Relationship of dementia and visual hallucinations in tremor and non-tremor dominant Parkinson's disease.

OBJECTIVES: Both visual hallucinations and cognitive dysfunction are experienced by a significant number of patients with Parkinson's disease. There were three main objectives of this study: (1) to determine if there is a difference in the prevalence of dementia in patients with tremor versus non-tremor dominant Parkinson's; (2) to determine if there is a difference of prevalence of visual hallucinations in patients with tremor and non-tremor dominant Parkinson's disease; and (3) to determine if there is a relationship between visual hallucinations and dementia in Parkinson's disease patients. BACKGROUND: Dementia and visual hallucinations are common non-motor symptoms of Parkinson's disease that affect a significant number of patients. Previous research has shown that visual hallucinations may be predictive of future onset of dementia. We wanted to compare the prevalence of these non-motor symptoms in tremor vs. non-tremor dominant Parkinson's disease, although previous research has shown that dementia may be more common in the akinetic rigid variant of Parkinson's disease without tremor. Visual hallucinations have not yet been studied in this way. METHODS: We performed a retrospective chart analysis on 314 patients with Parkinson's disease in this study. Patients meeting the inclusion criteria were stratified into several categories based on the presence or absence of tremor dominant PD, akinetic rigid dominant PD, dementia and visual hallucinations. Nonparametric tests were used for performing statistical analyses. The Chi Squared test was used for the analysis of categorical variables. RESULTS: Patients without tremor had a higher prevalence of dementia (29%) than those with tremor (14%). There was no difference in visual hallucinations in tremor versus non-tremor patients, although there was a significant trend between tremor and visual hallucinations in female patients. A significant correlation was found between dementia and visual hallucinations in the sample, however further investigation showed this was largely associated with female Parkinson's disease patients.

Gender differences in motor and non-motor symptoms among Sardinian patients with Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) occurs more frequently in men than in women and a higher risk for PD development in males compared with females has been hypothesized, suggesting gender may be a significant factor in the development and progression of parkinsonism. To date, gender differences in non-motor symptoms are under-reported. OBJECTIVE: To assess gender differences in motor and non-motor symptoms among Sardinian PD patients. METHODS: One hundred fifty-six (91 male and 65 female) consecutive Sardinian PD outpatients were included in this analysis. Modified Hoehn and Yahr scale and UPDRS were used to assess motor symptoms, while non-motor disturbances were evaluated with the non-motor symptoms scale (NMSS). Presence of depression, anxiety and other iatrogenic behavioral disorders was also investigated. In order to determine how gender differences could be specific to PD, 132 age-matched normal controls were assessed with the NMSS. RESULTS: Women were more likely than men to present with tremor as initial symptom (p<.025) and worse UPDRS instability score (p<.02). NMSS score in females was significantly higher than that in males (p<.018). A significantly higher severity in cardiovascular (p<0.002), sleep/fatigue (p<.018) and mood/apathy (p<.001) domains was observed in female PD patients, while the sexual dysfunction domain was reported with a significantly higher score in male patients (p<.017). Fatigue (p<.03), lack of motivation (p<.015) and sadness (p<.009) were observed significantly more frequent in females, while altered interest in sex was noted as more common in males (p<.001). Frequency of depression (p<.011) and anxiety (p<.001) was significantly higher in females, while male patients had increased frequency of compulsive sexual behaviors (p<.05). There was a significantly higher frequency of non-motor symptoms in eight domains in both male and female PD patients compared with controls (p<.001, for all comparisons, with the exception of urinary disturbances in females: p<.004). Only sexual dysfunctions were not significantly higher in male and female PD patients compared with controls. DISCUSSION: The present study highlights the role of gender differences associated with the occurrence of motor and non-motor disorders and our findings indicate that spectrum and severity of non-motor symptoms may present with different gender distribution in PD patients, suggesting a possible sex-related effect.

Reduced muscle strength is the major determinant of reduced leg muscle power in Parkinson's disease.

BACKGROUND: Reduced muscle power (speed × strength) is associated with increased fall risk and reduced walking speed in people with Parkinson's disease (PD) as well as in the general older population. This study aimed to determine the relative contribution of motor impairments (bradykinesia, tremor, rigidity and weakness) to reduced leg muscle power in people with PD. METHODS: Eighty-two people with PD were tested while "on" medication. Leg extensor muscle strength and muscle power were measured using pneumatic variable resistance equipment. Lower limb bradykinesia, rigidity and tremor were measured using the Movement Disorders Society-sponsored Unified Parkinson's Disease Rating Scale. Associations between motor impairments and leg muscle power were examined using linear regression. RESULTS: Univariate models revealed that muscle strength (R(2) = 0.84), bradykinesia (R(2) = 0.05) and rigidity (R(2) = 0.05) were significantly associated with leg muscle power, while tremor was not. A multivariate model including bradykinesia, tremor, rigidity, muscle strength, age and gender explained 89% of the variance in leg muscle power. This model revealed reduced muscle strength to be the major determinant of reduced muscle power (ß = 0.7), while bradykinesia was a minor contributor to reduced muscle power (ß = -0.1), even when accounting for age and gender. CONCLUSIONS: The findings that reduced strength and bradykinesia contribute to reduced muscle power in people with PD tested "on" medication suggest that these impairments are potential targets for physical interventions.

PET studies in Parkinson's disease motor and cognitive dysfunction.

Positron emission tomography (PET) has led to significant advances in the knowledge of the neurobiology and pathophysiology of Parkinson's disease (PD) and has also greatly contributed to the understanding of potential mechanisms involved in the development of treatment-induced complications. Initially, PET was mostly used to assess in vivo the severity of the nigrostriatal dopaminergic dysfunction and the resulting motor symptomatology in PD. It has been demonstrated that PET measurements of putaminal dopaminergic function, as measured by [(18)F]-Fluorodopa uptake, correlate well with stages of disease and symptom severity in PD patients, particularly with bradykinesia and rigidity. Analysis of metabolic changes across the brain has identified specific brain networks associated with the main motor features of the disease, including bradykinesia and tremor. In more recent years, the growing availability of new imaging radiotracers for monoaminergic and cholinergic neurons has enabled the evaluation of the non-dopaminergic brain pathways that are likely to be involved in the pathophysiology of non motor symptoms of PD, including depression, fatigue, sleep disorders, and cognitive impairment. Finally, ß-amyloid imaging agents have been used to assess the influence of coexistent cortical Alzheimer pathology in PD. This review summarizes the findings from PET studies that have investigated pathophysiology and treatment of motor dysfunction and cognitive impairment in PD.

Relación entre el tipo y lado de inicio de la sintomatología motora con la frecuencia de síntomas no motores en la enfermedad de Parkinson / Relationship between the type and side of motor symptoms with the prevalence of non-motor symptoms in Parkinson's disease

Introducción: la relación de la lateralidad y asimetría de la enfermedad de Parkinson con la sintomatología de disfunción no motora ha sido abordada principalmente desde el punto de vista de las funciones cognitivas, y los escasos estudios que han involucrado otros síntomas han sido contradictorios. La asociación de los síntomas no motores con el tipo de inicio de la enfermedad no ha sido estudiada profundamente. Objetivo: analizar la asociación entre el lado de inicio de la sintomatología motora, así como del tipo de inicio termorígeno y rígido-bradicinético y la prevalencia de síntomas no motores. Pacientes y métodos: se incluyeron 232 pacientes con diagnóstico de enfermedad de Parkinson. Se documentó el tipo de inicio y el hemicuerpo afectado inicialmente. La presencia de síntomas no motores se determinó mediante la aplicación del cuestionario de síntomas no motores (NMSQuest). Resultados: al analizar el lado de inicio y la presencia de los síntomas no motores explorados se encontraron diferencias estadísticamente significativas en la frecuencia de alucinaciones (p=0,04) y del trastorno conductual del sueño (p<0,01) en los sujetos de inicio del lado derecho. En el caso del tipo de inicio no se encontraron diferencias con significación estadística. Conclusiones: los sujetos con inicio en el hemicuerpo derecho parecen tener un mayor riesgo de presentar tanto alucinaciones como trastorno conductual del sueño. El médico tratante debe buscar de forma intencionada estos síntomas en estos pacientes, y de esta manera otorgar un tratamiento adecuado que impacte en la calidad de vida de los mismos (AU)

Introduction: The relationship between laterality and asymmetry of Parkinson's disease and non-motor dysfunction has been studied mainly from the perspective of cognitive functions, and the few studies that have included other symptoms have mixed reports. The relationship between non-motor symptoms and the type of onset of the disease has not been studied in detail. Objective: to analyse the association between the side and type of motor onset and the prevalence of non-motor symptoms. Patients and methods: we included 232 patients diagnosed with Parkinson's disease. Type of onset and the side initially affected were documented. The presence of non-motor symptoms was determined by applying the non-motor symptom questionnaire (NMSQuest). Results: when analysing the side of onset and presence of each non-motor symptom explored, statistically significant differences were found in the frequency of hallucinations (P=0.04) and sleep behaviour disorder (P<0.01) in subjects with right side onset. The motor type of onset differences were not statistically significant. Conclusions: subjects with right side onset seem to have a higher risk of having hallucinations and sleep behaviour disorders. These symptoms should be intentionally sought in order to provide treatment and improve the patient's quality of life (AU)

Course in Parkinson disease subtypes: A 39-year clinicopathologic study.

BACKGROUND: Individual variations in the course of Lewy body Parkinson disease (PD) are well known. Patients have been classified into different clinical subtypes to identify differences in the course among the subgroups. Several studies indicate that the outcome is more favorable in tremor dominant (TD) cases but others report no difference. A majority of progression studies are based on cross-sectional single point data or short-term clinical observations. The lack of longitudinally followed autopsy-confirmed PD cohort remains a major weakness in the literature. Biochemical studies of brain indicate most pronounced abnormalities in akinetic/rigid (AR) and the least in TD cases. We postulate that PD course in these subtypes is concordant with the biochemical findings. OBJECTIVE: To compare the course in TD, mixed (MX), and AR subtypes of PD. METHODS: Longitudinal clinical follow-up and autopsy studies were performed on 166 patients with PD over 39 years (1968-2006). Patients were classified into TD, AR, and MX based on the entire clinical course. Only the pathologically confirmed PD cases were included. RESULTS: Sixty-six percent of cases had MX, 26% AR, and 8% TD profile. The age at onset was younger (p < 0.001) and progression to Hoehn & Yahr stage 4 was slower (p = 0.016) in the TD cases. Dementia was most common in AR (p = 0.039) and the least common in TD. In general, the course was most favorable in TD, followed by MX and AR subgroups. CONCLUSION: The three subtypes of Parkinson disease have different courses which are concordant with the differences in brain biochemical abnormalities.

Movement disturbances in the differential diagnosis of Creutzfeldt-Jakob disease.

Movement disturbances are common in dementia disorders and are a central feature of the clinical classification criteria of Creutzfeldt-Jakob disease (CJD). Polymorphism at codon 129 of the prion protein gene is known to determine the clinical picture of CJD. The frequency and characteristics of movement disturbances in other dementing disorders, such as Alzheimer's disease (AD), is barely known and leads to misdiagnoses. We investigated the occurrence and characteristics of movement disturbances in 143 patients neuropathologically confirmed with CJD (n = 100), AD (n = 29), dementia with Lewy bodies (DLB) (n = 7), or other diagnoses (n = 7). All patients had been referred with the differential diagnosis of prion disease. Ataxia and dysmetria were significantly more frequent in CJD than in AD or DLB patients, whereas hypokinesia was up to five times more frequent in AD or DLB (P < 0.05). Using an ordered logistic regression to identify constellations of movement disturbances, the diagnosis of CJD was likely in patients presenting ataxia but not hypokinesia. The reverse situation was statistically associated with AD. Ataxia and cogwheel rigidity were associated with valine-homozygosity and akinesia with methionine-homozygosity in the CJD patients. Our results indicate that the careful assessment of movement disturbances may be helpful in the differential diagnosis of Creutzfeldt-Jakob disease.

REM sleep behaviour disorder in Parkinson's disease is associated with specific motor features.

BACKGROUND: Rapid eye movement (REM) sleep behaviour disorder (RBD) is commonly associated with Parkinson's disease (PD), and recent studies have suggested that RBD in PD is associated with increased cognitive impairment, waking EEG slowing, autonomic impairment and lower quality of life on mental health components. However, it is unclear whether the association of RBD in PD has implications for motor manifestations of the disease. METHODS: The study evaluated 36 patients with PD for the presence of RBD by polysomnography. Patients underwent an extensive evaluation on and off medication by a movement disorders specialist blinded to the polysomnography results. Measures of disease severity, quantitative motor indices, motor subtypes, complications of therapy and response to therapy were assessed and compared using regression analysis that adjusted for disease duration and age. RESULTS: Patients with PD and RBD were less likely to be tremor predominant (14% vs 53%; p<0.02) and had a lower proportion of their Unified Parkinson Disease Rating Scale (UPDRS) score accounted for by tremor (8.2% vs 19.0%; p<0.01). An increased frequency of falls was noted among patients with RBD (38% vs 7%; p = 0.04). Patients with RBD demonstrated a lower amplitude response to their medication (UPDRS improvement 16.2% vs 34.8%; p = 0.049). Markers of overall disease severity, quantitative motor testing and motor complications did not differ between groups. CONCLUSIONS: The presence of altered motor subtypes in PD with RBD suggests that patients with PD and RBD may have a different underlying pattern of neurodegeneration than PD patients without RBD.

Death, child abuse, and adverse neurological outcome of infants after an apparent life-threatening event.

OBJECTIVES: Apparent life-threatening events in infants constitute a significant challenge for health care providers. Apparent life-threatening event evaluation and management are poorly defined, and outcomes have not been clearly determined. Our objectives were to characterize short- and long-term risks for death, child abuse, and abnormal neurological outcomes of infants after an apparent life-threatening event and to identify clinical features that are predictive of these outcomes. METHODS: We collected data from infants ages birth to 12 months of age who were hospitalized after an apparent life-threatening event during a 5-year time period. Patients were evaluated for subsequent death, child abuse, or adverse neurological outcome (chronic epilepsy or developmental delay). RESULTS: A total of 471 patients met inclusion criteria and were followed an average of 5.1 years. Two patients died after developing chronic epilepsy and severe developmental delay. Fifty-four (11%) patients were diagnosed as being a victim of child abuse, but only 2 were identified at initial presentation. There were 23 (4.9%) patients with adverse neurological outcomes, including 17 (3.6%) with chronic epilepsy and 14 (3.0%) with developmental delay. Of those who developed chronic epilepsy, 71% returned within 1 month of the initial apparent life-threatening event with a second event. Neurological evaluation at the time of the apparent life-threatening event had low yield for predicting those who would develop chronic epilepsy. CONCLUSIONS: Infants who suffer an apparent life-threatening event are at risk for subsequent child abuse and adverse neurological outcomes. Deaths were uncommon and only occurred in the setting of severe developmental delay and seizure disorders. Neurological evaluation during hospitalization for a first apparent life-threatening event is of low yield, but close follow-up is essential.

Odor identification and progression of parkinsonian signs in older persons.

The authors tested the hypothesis that difficulty in identifying odors, a common finding in Parkinson's disease, is associated with more rapid progression of parkinsonian signs in 743 community-dwelling older people without dementia or Parkinson's disease at study onset. Odor identification ability was assessed at baseline with the 12-item Brief Smell Identification Test (mean = 9.0 correct, SD = 2.1), and parkinsonism was assessed annually for up to 5 years with a modified version of the Unified Parkinson's Disease Rating Scale. In an analysis adjusted for age, sex, and education, lower odor identification score was related to higher level of global parkinsonism at baseline (p < .001) and more rapid progression of global parkinsonism on follow-up (p = .002). This result mainly reflected an association of odor identification with worsening parkinsonian gait. The results suggest that impaired odor identification is associated with more rapid progression of parkinsonism in old age, particularly parkinsonian gait disturbance.