Automated and manual hippocampal segmentation techniques: Comparison of results, reproducibility and clinical applicability.

BACKGROUND: Imaging techniques used to measure hippocampal atrophy are key to understanding the clinical progression of Alzheimer's disease (AD). Various semi-automated hippocampal segmentation techniques are available and require human expert input to learn how to accurately segment new data. Our goal was to compare 1) the performance of our automated hippocampal segmentation technique relative to manual segmentations, and 2) the performance of our automated technique when provided with a training set from two different raters. We also explored the ability of hippocampal volumes obtained using manual and automated hippocampal segmentations to predict conversion from MCI to AD. METHODS: We analyzed 161 1.5 T T1-weighted brain magnetic resonance images (MRI) from the ADCS Donepezil/Vitamin E clinical study. All subjects carried a diagnosis of mild cognitive impairment (MCI). Three different segmentation outputs (one produced by manual tracing and two produced by a semi-automated algorithm trained with training sets developed by two raters) were compared using single measure intraclass correlation statistics (smICC). The radial distance method was used to assess each segmentation technique's ability to detect hippocampal atrophy in 3D. We then compared how well each segmentation method detected baseline hippocampal differences between MCI subjects who remained stable (MCInc) and those who converted to AD (MCIc) during the trial. Our statistical maps were corrected for multiple comparisons using permutation-based statistics with a threshold of p < .01. RESULTS: Our smICC analyses showed significant agreement between the manual and automated hippocampal segmentations from rater 1 [right smICC = 0.78 (95%CI 0.72-0.84); left smICC = 0.79 (95%CI 0.72-0.85)], the manual segmentations from rater 1 versus the automated segmentations from rater 2 [right smICC = 0.78 (95%CI 0.7-0.84); left smICC = 0.78 (95%CI 0.71-0.84)], and the automated segmentations of rater 1 versus rater 2 [right smICC = 0.97 (95%CI 0.96-0.98); left smICC = 0.97 (95%CI 0.96-0.98)]. All three segmentation methods detected significant CA1 and subicular atrophy in MCIc compared to MCInc at baseline (manual: right pcorrected = 0.0112, left pcorrected = 0.0006; automated rater 1: right pcorrected = 0.0318, left pcorrected = 0.0302; automated rater 2: right pcorrected = 0.0029, left pcorrected = 0.0166). CONCLUSIONS: The hippocampal volumes obtained with a fast semi-automated segmentation method were highly comparable to the ones obtained with the labor-intensive manual segmentation method. The AdaBoost automated hippocampal segmentation technique is highly reliable allowing the efficient analysis of large data sets.

Associations between hippocampal morphometry and neuropathologic markers of Alzheimer's disease using 7 T MRI.

Hippocampal atrophy, amyloid plaques, and neurofibrillary tangles are established pathologic markers of Alzheimer's disease. We analyzed the temporal lobes of 9 Alzheimer's dementia (AD) and 7 cognitively normal (NC) subjects. Brains were scanned post-mortem at 7 Tesla. We extracted hippocampal volumes and radial distances using automated segmentation techniques. Hippocampal slices were stained for amyloid beta (Aß), tau, and cresyl violet to evaluate neuronal counts. The hippocampal subfields, CA1, CA2, CA3, CA4, and subiculum were manually traced so that the neuronal counts, Aß, and tau burden could be obtained for each region. We used linear regression to detect associations between hippocampal atrophy in 3D, clinical diagnosis and total as well as subfield pathology burden measures. As expected, we found significant correlations between hippocampal radial distance and mean neuronal count, as well as diagnosis. There were subfield specific associations between hippocampal radial distance and tau in CA2, and cresyl violet neuronal counts in CA1 and subiculum. These results provide further validation for the European Alzheimer's Disease Consortium Alzheimer's Disease Neuroimaging Initiative Center Harmonized Hippocampal Segmentation Protocol (HarP).

Cognitive and behavioral symptoms in Parkinson's disease patients with the G2019S and R1441G mutations of the LRRK2 gene.

OBJECTIVE: To compare the cognitive and psychiatric status of patients with Parkinson's disease related to the G2019S and the R1441G mutations of the LRRK2 gene (LRRK2-PD) and idiopathic Parkinson's disease (iPD) patients. METHODS: We examined cognition and psychiatric symptoms in 27 patients with LRRK2-PD (12 G2019S and 15 R1441G) and 27 iPD patients. RESULTS: The groups were similar in age, education, disease duration, levodopa equivalent daily dose, and Unified Parkinson's Disease Rating Scale (UPDRS) II-IV; however, the LRRK2-PD showed less impairment on UPDRS-I (2.0 ± 1.7 vs. 4.2 ± 2.8, p = 0.003). The LRRK2-PD presented less frequent subjective cognitive complaints (18.5% vs. 63.0%, p = 0.002), and mild cognitive impairment or dementia (25.9% vs. 59.2%, p = 0.027). They also showed less impairment on scales for general cognition (Mattis dementia rating scale 131.2 ± 10.9 vs. 119 ± 24.0, p = 0.022), episodic verbal memory (Rey's auditory verbal learning test, immediate recall 39.2 ± 9.5 vs. 27.6 ± 12.8 p < 0.001, delayed recall 7.2 ± 3.7 vs. 4.7 ± 4.0 p = 0.022), and the Neuropsychiatric Inventory (9.7 ± 9.2 vs. 20.5 ± 14.3, p = 0.004, significant differences for apathy and hallucinations). The LRRK2-PD subjects were less frequently treated with antipsychotic medication (0% vs. 25.9%, p = 0.010). There were no significant differences between G2019S and R1441G mutation carriers. CONCLUSIONS: Mutations of the LRRK2 gene might cause PD associated with less cognitive and neuropsychiatric impairment as compared to iPD.

Relationship between hippocampal atrophy and neuropathology markers: a 7T MRI validation study of the EADC-ADNI Harmonized Hippocampal Segmentation Protocol.

OBJECTIVE: The pathologic validation of European Alzheimer's Disease Consortium Alzheimer's Disease Neuroimaging Initiative Center Harmonized Hippocampal Segmentation Protocol (HarP). METHODS: Temporal lobes of nine Alzheimer's disease (AD) and seven cognitively normal subjects were scanned post-mortem at 7 Tesla. Hippocampal volumes were obtained with HarP. Six-micrometer-thick hippocampal slices were stained for amyloid beta (Aß), tau, and cresyl violet. Hippocampal subfields were manually traced. Neuronal counts, Aß, and tau burden for each hippocampal subfield were obtained. RESULTS: We found significant correlations between hippocampal volume and Braak and Braak staging (ρ = -0.75, P = .001), tau (ρ = -0.53, P = .034), Aß burden (ρ = -0.61, P = .012), and neuronal count (ρ = 0.77, P < .001). Exploratory subfield-wise significant associations were found for Aß in Cornu Ammonis (CA)1 (ρ = -0.58, P = .019) and subiculum (ρ = -0.75, P = .001), tau in CA2 (ρ = -0.59, P = .016), and CA3 (ρ = -0.5, P = .047), and neuronal count in CA1 (ρ = 0.55, P = .028), CA3 (ρ = 0.65, P = .006), and CA4 (ρ = 0.76, P = .001). CONCLUSIONS: The observed associations provide pathological confirmation of hippocampal morphometry as a valid biomarker for AD and pathologic validation of HarP.

Autonomic dysfunction in parkinsonian LRRK2 mutation carriers.

INTRODUCTION: The aim of this study was to compare autonomic function in PD symptomatic carriers of the LRRK2 mutations and idiopathic Parkinson's disease (iPD) patients. MATERIAL AND METHODS: We studied 25 PD patients: 12 with the LRRK2 mutation (6 G2019S and 6 R1441G), and 13 with iPD. All patients underwent blood pressure and heart rate monitoring during head up tilt, Valsalva maneuver and deep breathing, along with recording of sympathetic skin response (SSR) and cardiac MIBG scintigraphy. RESULTS: Three of the patients with iPD and one of the LRRK2 carriers had orthostatic hypotension. Arterial pressure "overshoot" during phase IV of Valsalva maneuver was less pronounced in patients with iPD. During passive tilt, LRRK2 carries had higher increase of blood pressure than iPD patients MIBG late myocardial/mediastinal uptake ratios were higher in LRRK2 mutation carriers (1.51 ± 0.28 vs 1.32 ± 0.25; p < 0.05). DISCUSSION: Carriers of the LRRK2 mutation had less autonomic impairment than those with iPD as shown by higher cardiac MIBG uptake and a tendency to less impairment of autonomic non-invasive tests. It is important to carry out larger studies comparing the clinical, functional and pathological characteristics of these patients.

Cerebrospinal fluid Aß levels correlate with structural brain changes in Parkinson's disease.

ParkWest is a large Norwegian multicenter study of newly diagnosed drug-naïve subjects with Parkinson's disease (PD). Cognitively normal PD subjects (PDCN) and PD subjects with mild cognitive impairment (PDMCI) from this cohort have significant hippocampal atrophy and ventricular enlargement, compared to normal controls. Here, we aimed to investigate whether the same structural changes are associated with cerebrospinal fluid (CSF) levels of amyloid beta (Aß)38 , Aß40 , Aß42 , total tau (t-tau), and phosphorylated tau (p-tau). We performed three-dimensional radial distance analyses of the hippocampi and lateral ventricles using the MRI data from ParkWest subjects who provided CSF at baseline. Our sample consisted of 73 PDCN and 18 PDMCI subjects. We found significant associations between levels of all three CSF Aß analytes and t-tau and lateral ventricular enlargement in the pooled sample. In the PDCN sample, all three amyloid analytes showed significant associations with the radial distance of the occipital and frontal horns of the lateral ventricles. CSF Aß38 and Aß42 showed negative associations, with enlargement in occipital and frontal horns of the lateral ventricles in the pooled sample, and a negative association with the occipital horns in PDMCI. CSF Aß levels in early PD correlate with ventricular enlargement, previously associated with PD dementia. Therefore, CSF and MRI markers may help identify PD patients at high risk for developing cognitive decline and dementia in the course of their illness. Contrary to Alzheimer's disease, we found no associations between CSF t-tau and p-tau and hippocampal atrophy.

Nocturnal hypertension and dysautonomia in patients with Parkinson's disease: are they related?

Orthostatic hypotension and supine hypertension frequently coexist in Parkinson's disease (PD) patients, leading to visceral damage and increased mortality rates. The aim of this paper is to analyze the frequency and association of both conditions in a sample of outpatients with PD. A total of 111 patients, diagnosed with PD, were studied. Disease duration, treatment, cardiovascular risk factors, UPDRS I-IV and Scopa Aut scale scores were reported. Subjects underwent 24-h ambulatory blood pressure (BP) monitoring and were assessed for orthostatic hypotension. We compared our results with those published in 17,219 patients using the same protocol and the same type of device. Overall, 71.1 % had no proper circadian rhythm. This frequency was significantly higher than that of the control population (48 %). The prevalence of the nondipper or riser patterns was higher in patients with orthostatic hypotension (77.8 vs. 66.7 %). There was a correlation between nightly increases in diastolic blood pressure and changes in BP during the orthostatic test. Patients taking higher doses of treatment had less decreases in SBP (cc:-0.25; p = 0.007) and DBP (cc:-0.33; p < 0.001) at night, however there was no relation with drug type. The majority of patients with Parkinson's disease show an altered circadian rhythm of blood pressure. Patients with a non-dipper or riser pattern on 24 h ABPM exhibited a higher prevalence of autonomic disorders (orthostatic hypotension) and received higher doses of dopaminergic treatment. A day-night variation in diastolic blood pressure was the most important marker of these findings.

Cardiac sympathetic denervation in symptomatic and asymptomatic carriers of the E46K mutation in the α synuclein gene.

OBJECTIVE: The aim of this study was to analyze autonomic function and cardiac sympathetic innervation in symptomatic and asymptomatic carriers of the E46K alpha-synuclein gene (SNCA) mutation. PATIENTS AND METHODS: Autonomic function tests were performed in six patients, four of whom were symptomatic carriers (ages: 46, 59, 52 and 28-years) and two who were asymptomatic carriers (ages: 52 and 29 years). Autopsy studies were performed on an additional two symptomatic carriers not eligible for autonomic testing. Patients completed the SCOPA autonomic questionnaire, and underwent the head-up tilt test accompanied by measurements of plasma norepinephrine. Valsalva maneuver and deep breathing tests, along with recording of sympathetic skin response (SSR) and cardiac MIBG scintigraphy were carried out. Myocardial tissue sections removed from the two autopsied cases were subjected to routine histological staining and immunohistochemical processing with monoclonal antibodies against tyrosine hydroxylase and alpha-synuclein. RESULTS: Both the four symptomatic and the older asymptomatic carriers reported abnormalities in the SCOPA questionnaire and had markedly diminished cardiac MIBG uptake. Plasma norepinephrine in the supine and tilted positions was normal in all subjects. Only one patient had significant orthostatic hypotension. There was a complete absence of tyrosine hydroxylase immunostaining in the myocardium of the two autopsied cases. INTERPRETATION: We have found imaging and histological evidence of cardiac sympathetic denervation in symptomatic and asymptomatic carriers of the E46K alpha-synuclein gene mutation. The sympathetic denervation appears to be organ-specific, with selective affectation of the heart given that plasma norepinephrine levels and blood pressure were normal.

Verbal memory is associated with structural hippocampal changes in newly diagnosed Parkinson's disease.

BACKGROUND AND OBJECTIVE: Cognitive impairment, including impairment of episodic memory, is frequently found in newly diagnosed Parkinson's disease (PD). In this longitudinal observational study we investigated whether performance in memory encoding, retention, recognition and free recall is associated with reduced hippocampal radial distance. METHODS: We analysed baseline T1-weighted brain MRI data from 114 PD subjects without cognitive impairment, 29 PD subjects with mild cognitive impairment and 99 normal controls from the ParkWest study. Age- and education-predicted scores for the California Verbal Learning Test 2 (CVLT-2) and tests of executive function were regressed against hippocampal radial distance while adjusting for imaging centre. RESULTS: There was no association between encoding or performance on executive tests and hippocampal atrophy in the PD group. In the full PD sample we found bilaterally significant associations between lower delayed free recall scores and hippocampal atrophy in the CA1, CA3 and subiculum area (left, p=0.0013; right, p=0.0082). CVLT-2 short delay free recall scores were associated with bilateral hippocampal CA1 and subicular atrophy in the full PD sample (left, p=0.013; right, p=0.047). CVLT-2 recognition scores showed a significant association with right-sided subicular and CA1 atrophy in the full PD sample (p=0.043). CONCLUSIONS: At the time of PD diagnosis, subjects' verbal memory performance in recall and recognition are associated with atrophy of the hippocampus, while encoding is not associated with hippocampal radial distance. We postulate that impaired recall and recognition might reflect deficient memory consolidation at least partly due to structural hippocampal changes.

Neuropsychiatric symptoms in amnestic mild cognitive impairment: increased risk and faster progression to dementia.

INTRODUCTION: Neuropsychiatric symptoms (NPS) are common in mild cognitive impairment (MCI) but its role as a predictive factor for the progression to dementia is still not clear. The objective of this study is to identify NPS that predict the progression from amnestic MCI (a-MCI) to dementia using an easy to administer screening tool for NPS. MATERIAL AND METHODS: 132 patients with a-MCI were assessed for NPS by the Neuropsychiatric Inventory (NPI) and followed to detect progression to dementia. RESULTS: The mean follow-up time was 3.5±2.9 years and rate of progression to dementia 28.8%. Two items of NPI were found to be independent risk factors for progression, nighttime behavioural disturbance (hazard ratio(HR)=2.2, 95%CI=1.10-4.43), anxiety (HR=2.5, 95%CI=1.01-6.20) and apathy (HR=2.2, 95%CI=1.003-4.820). The risk of progression increased with higher score on NPI (HR=1.046 per point, 95%CI=1.019- 1.073), and with a higher number of items of NPI affected (HR=3.6 per item, 95%CI=2.0-6.4). Faster progression to dementia was observed in patients with either nighttime behavioural disturbance, apathy or anxiety (4.6 vs. 8.3 years, 5.3 vs. 8.4 years and 3.0 vs. 7.7 years respectively, p < 0.01) as well as in those with a higher number of items affected (no items = 9.2 years, 1-3 items = 6.6 years and > 3 items = 2.9 years, p < 0.001). CONCLUSIONS: Assessing a broad spectrum of NPS can help identify patients with a-MCI presenting a higher risk for progression to dementia. This can be useful to select patients for closer follow-up, clinical trials and future therapeutic interventions.

The applause sign and neuropsychological profile in progressive supranuclear palsy and Parkinson's disease.

BACKGROUND: The applause sign has been associated with various neurodegenerative diseases. We investigate its validity in the differential diagnosis of progressive supranuclear palsy and Parkinson's disease, and its relationship with neuropsychological tests. PATIENTS AND METHODS: 23 patients with progressive supranuclear palsy and 106 patients with Parkinson's disease were included and administered the following scales: progressive supranuclear palsy rating scale, unified Parkinson's disease rating scale (UPDRS), mini-mental state examination (MMSE), frontal assessment battery (FAB), neuropsychiatric inventory and three-clap test. RESULTS: 73.9% with progressive supranuclear palsy and 21.7% with Parkinson's disease showed a positive applause sign. Only a positive applause sign, UPDRS II score and disease duration were found to be predictors of progressive supranuclear palsy. Both patient-groups showed statistically significant correlations between the applause sign and neuropsychological tests: in progressive supranuclear palsy patients MMSE correlation coefficient: 0.62 (p: 0.002) and FAB correlation coefficient: 0.48 (p: 0.02), and in Parkinson's disease patients MMSE correlation coefficient: 0.47 (p<0.001) and FAB correlation coefficient: 0.43 (p<0.001). Verbal fluency and inhibitory control (FAB) and writing and orientation in time (MMSE) discriminated between patients with normal and positive applause sign. CONCLUSIONS: A positive applause sign is not specific to progressive supranuclear palsy and may also be observed in Parkinson's disease patients with altered cognition, and it's related to cortical frontal abnormalities such as language disorders and inhibitory control.

Comparing hippocampal atrophy in Alzheimer's dementia and dementia with lewy bodies.

BACKGROUND/AIMS: Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) are the two most common neurodegenerative dementias. During the early stages, clinical distinction between them is often challenging. Our objective is to compare hippocampal atrophy patterns in mild AD and mild DLB. We hypothesized that DLB subjects have milder hippocampal atrophy relative to AD subjects. METHODS: We analyzed the T1-weighted magnetic resonance imaging data from 113 subjects: 55 AD, 16 DLB and 42 cognitively normal elderly (normal controls, NC). Using the hippocampal radial distance technique and multiple linear regression, we analyzed the effect of clinical diagnosis on hippocampal radial distance, while adjusting for gender and age. Three-dimensional statistical maps were adjusted for multiple comparisons using permutation-based statistics with a threshold of p < 0.01. RESULTS: Compared to NC, AD exhibited significantly greater atrophy in the cornu ammonis (CA)1, CA2-3 and subicular regions bilaterally while DLB showed left-predominant atrophy in the CA1 region and subiculum. Compared directly, AD and DLB did not reveal statistically significant differences. CONCLUSION: Hippocampal atrophy, while present in mildly impaired DLB subjects, is less severe than atrophy seen in mildly impaired AD subjects, when compared to NC. Both groups show predominant atrophy of the CA1 subfield and subiculum.

SCOPA-AUT scale in different parkinsonisms and its correlation with (123) I-MIBG cardiac scintigraphy.

INTRODUCTION: Our objective was to assess the usefulness of the Scales for Outcomes in Parkinson's disease - Autonomic (SCOPA-AUT) in the differential diagnosis of Parkinsonisms and clarify its relation with 123-I-MIBG cardiac scintigraphy. METHODS: A total of 112 patients with Parkinson's disease (PD), 12 with multiple system atrophy parkinsonian variant (MSA-P) and 20 with progressive supranuclear palsy (PSP) participated in the study. The following variables were collected: age, sex, age at onset, length of illness, type and dose of anti-Parkinson medication, and score on the Unified Parkinson's Disease Rating Scale. The Unified Multiple System Atrophy Rating Scale was administered to patients with MSA and the Progressive Supranuclear Palsy Rating Scale to those with PSP. Finally, the SCOPA-AUT was administered to all the patients. Cardiac 123I-MIBG SPECT scans were performed on a subset of patients (25 with PD and 5 with MSA-P). RESULTS: Statistically significant differences were observed (p < 0.01) in the SCOPA-AUT scores between patients with PD (14.75+/-8.09) and those with MSA (21.07+/-5.56), the latter having higher scores on the bowel function (20.07+/-13.40 vs 34.92+/-14.91) and urinary domains (30.21+/-21.55 vs 49.26+/-21.40) (p < 0.01). No correlation was found between the SCOPA-AUT score and anti-Parkinson's medication and heart:mediastinum (H/M) MIBG uptake ratio in the cardiac SPECT (at 4 h). DISCUSSION: Severity of dysautonomia as measured by the SCOPA-AUT was not correlated with clinical severity, time since onset or the H/M ratio. In the patients with PD, the only variable associated with the H/M ratio was age at onset of the disease.

Initial neuropsychological impairments in patients with the E46K mutation of the α-synuclein gene (PARK 1).

INTRODUCTION: In 2004 we described the mutation E46K of the α-Synuclein (SNCA). These patients show Parkinson's disease with early cognitive impairment, sleep disorders and autonomic dysfunction. OBJECTIVE: The main objective is to identify early neuropsychological impairments in patients with the E46K mutation. METHODS: This is a longitudinal neuropsychological study of 4 of the 5 surviving patients with E46K mutation by semi-structured interviews and the following scales: Mattis Dementia Rating Scale (MDRS), semantic and phonemic verbal fluency tests (VFT), Benton Visual Retention Test (BVRT), Stroop Test (STROOP), Clock drawing test (CLOCK), WAIS III Letter and Number sequencing (WAIS III LN), Rey Auditory Verbal Learning Test (RAVLT) and Benton Judgement of Line Orientation Test (BJLOT). Motor status was assessed by UPDRS III. RESULTS: Motor status: Patients 1, 2 and 3 present mild to moderate Parkinson disease of 7, 8 and 3years of evolution respectively, patient 4 is asymptomatic. Cognitive status: Patient 2 and 3 both refer cognitive decline while patient 1 presents no cognitive complaints, however they all show a progressive cognitive decline across various tasks. Tests of frontal function showed the first alterations in all patients but fluctuate. The first cognitive complaints coincide with deterioration of tasks of posterior cortical basis. Patient 4 presents a normal performance on all tests. Patient 1, 2 and 3 have all presented visual hallucinations. CONCLUSIONS: A fluctuating frontal impairment is observed at early stages. Prominent visuospatial alterations and visual hallucinations suggest that posterior cortical dysfunction might be a distinct early feature of the cognitive impairment observed in patients with this mutation.

Impact of psychiatric symptoms and sleep disorders on the quality of life of patients with Parkinson's disease.

The objective of this study is to assess how the non-motor symptoms of Parkinson's disease (PD), such as depression, cognitive deterioration, neuropsychiatric and sleep disorders, affect the quality of life, and to compare them with the motor symptoms in order to determine their real impact. A cross-sectional study was designed including 99 patients (mean age 68.5 ± 9.9 years, duration of disease 8.7 ± 6.2 years). Demographic data, onset of PD, years on treatment with levodopa (LD), class of dopaminergic drug prescribed, and dosages were obtained. The following scales were used: quality of life (PDQ-39), Unified Parkinson's Disease Rating Scale (UPDRS I-IV), Parkinson Disease Sleep Scale (PDSS) and daytime sleepiness (Epworth), Mini-Mental State Examination, depression (HAM-D), and the neuropsychiatric inventory (NPI-10). The PDQ-39 summary index (PDQ-39 SI) was 24.7 ± 13.2. A linear regression model including all variables showed that four independent variables accounted for 67.2% of the variance in the PDQ-39 SI (F = 33,277; p < 0.001): NPI, PDSS, UPDRS IV, and UPDRS I. When sub-items of the NPI, PDSS and UPDRS IV scales are analyzed, significant correlations (p < 0.001) are found between the PDQ-39 SI and depression, agitation, apathy, anxiety, hallucinations, delusions, incontinence of urine, morning painful posturing, restlessness in bed, morning fatigue, duration of off periods, unpredictable and predictable off periods, early morning dystonia, and sudden off periods. Neuropsychiatric symptoms, especially depression, nighttime sleep disorders such as urinary incontinence, nighttime restlessness, morning fatigue and somnolence, off-period dystonia and motor fluctuations are the variables that most affect the quality of life of patients with PD.

Factors influencing the symmetry of Parkinson's disease symptoms.

INTRODUCTION: The presence of asymmetry in symptoms and clinical signs favours the diagnosis of Parkinson's disease (PD). The aim of this study is to analyse this symptom asymmetry as a function of different variables and compare it with other parkinsonisms. MATERIALS AND METHODS: 201 Patients with PD were studied. The sample was supplemented with 29 patients diagnosed with MSA-P (according to the criteria established by the American Academy of Neurology) and 17 with PSP (according to the criteria established by the NINDS-SPSP International Workshop). The symmetry was evaluated, based on items 20-23, 25 and 26 of the Unified Parkinson's Disease Rating Scale, by subtracting the motor score for the left side from that for the right side. Those patients with a difference of one point or more were designated as being asymmetric. RESULTS: Around 16.4% of patients presented symmetrical clinical symptoms. There were no differences between those patients with or without family history of the disease. Those patients with symmetric symptoms were found to have longer symptomatic disease duration (10.8 vs. 7.9 years), a worse mental state (UPDRS I: 3.9 vs. 3.2), a higher incidence of complications (UPDRS IV: 4.5 vs. 3.2) and had their activities of daily living (ADL) affected to a greater degree (UPDRS II: 13.0 vs. 11.0). Around 48.3% of the MSA-P patients and 52.9% of the PSP patients showed symmetric symptoms. CONCLUSIONS: The degree of symmetry is not useful in differentiating between sporadic and familial PD. However, the observation of highly symmetrical symptoms in a patient with short evolution time indicates that an atypical parkinsonism should be suspected.

Neuroleptic malignant syndrome and serotonin syndrome in a female patient: a clinicopathologic case.

We report the case of a 24-year-old female patient who initially developed a neuroleptic malignant syndrome after haloperidol exposure and experienced 6 years later a serotonin syndrome after repeated fluoxetine exposure. The patient did not respond to symptomatic treatment and died in this latter episode. At necropsy, no gross or microscopic changes were seen with conventional histological stains, and immunohistochemical stains were negative. This is the first clinicopathologic case of a patient who experienced both neuroleptic malignant and serotonin syndromes. We speculate that this case argue in favor that both syndromes share some fundamental pathogenetic mechanisms.

Application of depression criteria (DSM-IV) in patients with Parkinson's disease.

INTRODUCTION: The aim of this study is to analyze the clinical differences between Parkinson's disease patients with major (MD) and minor depression (md) and to see how both affect the quality of life. MATERIAL AND METHODS: 118 patients diagnosed with Parkinson's disease. The mean age of onset was 60.4+/-11.2 years with a mean duration of 8.5+/-6.2 years. Depression was diagnosed according to DSM-IV-TR criteria. Scores on the Hamilton depression inventory, MMSE, PDQ-39, NPI-10, UPDRS III, and UPDRS IV were recorded. RESULTS: Twenty-one patients (17.8%) met the criteria of major depression (MD) and 33 (28.0%) those of minor depression (md). The scores on the PDQ-39 and NPI-10 of patients with MD were higher than in patients with md, and control group. The MMSE scores were lower in patients with MD. In 52.2% of the patients with MD, the diagnosis of depression was made prior to that of PD, this occurred only in 24.2% of the patients with md (p<0.001). The presence of anhedonia was related to cognitive impairment and the presence of neuropsychiatric symptoms. DISCUSSION: MD is probably a part of the disease process of PD; it is associated with cognitive impairment and may precede motor symptoms.