Temperament and personality features in panic disorder with or without comorbid mood disorders

Personality and temperament features, assessed with the Structured Interview for DSM-III-R Personality Disorders — Revised (SIDP-R) and the Tridimensional Personality Questionnaire (TPQ), respectively, were evaluated in 62 patients affected by panic disorder with (PD+MD) (n= 22) or without comorbid mood disorder (PD) (n=40). A significant difference in the prevalence of personality disorders (PD+MD, 86% vs. PD, 62%; P <0.05), particularly dependent (PD+DM, 50% vs. PD, 17%; P < 0.01) and borderline (PD+DM, 9% vs. PD, 0%; P=0.05) personality disorders, was observed between the groups. Moreover, patients in the PD+MD group had higher scores for harm avoidance (PD+MD, 22.2±5.6 vs. PD, 26.9±5.1; P < 0.05) than patients in the PD group. The harm avoidance score in PD patients was significantly related to personality disorder and not to MD, suggesting that harm avoidance is not associated with greater severity of the illness. Our data confirm the hypothesis that subjects with higher harm avoidance scores have a greater probability of being affected by cluster C personality disorders and comorbid mood and anxiety disorders.     

Hyperhomocysteinemia in levodopa‐treated patients with Parkinson's disease dementia

Dementia is a frequent non‐motor feature of Parkinson's disease (PD). Elevated plasma homocysteine (Hcy) levels have been associated with both cognitive impairment and dementia. Increased Hcy levels have been observed in levodopa‐treated patients with PD. The objective of our study was to evaluate the association between plasma Hcy levels and dementia in PD. We performed a multicenter cross‐sectional study on patients with PD with (PDD) and without (PDnD) dementia and age‐ and sex‐matched healthy controls. We compared Hcy levels in patients with PDD and PDnD and healthy controls, and we performed logistic regression analysis to search for an association between the presence of dementia and increased Hcy levels in PD. Patients with PD (121), PDD (42), and PDnD (79), and age‐ and sex‐matched controls (154) were enrolled. Hcy levels were higher in patients with PD compared to controls (17.5 μmol/L ± 10.2 vs. 11 ± 4.1; P < 0.00001). Among patients with PD, Hcy levels were higher in the PDD group compared to the PDnD group (20.7 μmol/L ± 12.1 vs. 15.8 ± 8.5; P = 0.002). In a multivariate logistic regression model, higher Hcy levels [Odds ratios comparing the top (>18.9 μmol/L) with the bottom tertile (<12.4 μmol/L): 3.68; 95% CI: 1.14–11.83] were significantly associated with dementia. These data support the association between elevated Hcylevels and the presence of dementia in PD. © 2009 Movement Disorder Society     

Generalized and neurotransmitter‐selective noradrenergic denervation in Parkinson's disease with orthostatic hypotension

Patients with Parkinson's disease (PD) often have manifestations of autonomic failure. About 40% have neurogenic orthostatic hypotension (NOH), and among PD+NOH patients virtually all have evidence of cardiac sympathetic denervation; however, whether PD+NOH entails extra‐cardiac noradrenergic denervation has been less clear. Microdialysate concentrations of the main neuronal metabolite of norepinephrine (NE) and dihydroxyphenylglycol (DHPG) were measured in skeletal muscle, and plasma concentrations of NE and DHPG were measured in response to i.v. tyramine, yohimbine, and isoproterenol, in patients with PD+NOH, patients with pure autonomic failure (PAF), which is characterized by generalized catecholaminergic denervation, and control subjects. Microdialysate DHPG concentrations were similarly low in PD+NOH and PAF compared to control subjects (163 ± 25, 153 ± 27, and 304 ± 27 pg/mL, P < 0.01 each vs. control). The two groups also had similarly small plasma DHPG responses to tyramine (71 ± 58 and 82 ± 105 vs. 313 ± 94 pg/mL; P < 0.01 each vs. control) and NE responses to yohimbine (223 ± 37 and 61 ± 15 vs. 672 ± 130 pg/mL, P < 0.01 each vs. control), and virtually absent NE responses to isoproterenol (20 ± 34 and 14 ± 15 vs. 336 ± 78 pg/mL, P < 0.01 each vs. control). Patients with PD+NOH had normal bradycardia responses to edrophonium and normal epinephrine responses to glucagon. The results support the concept of generalized noradrenergic denervation in PD+NOH, with similar severity to that seen in PAF. In contrast, the parasympathetic cholinergic and adrenomedullary hormonal components of the autonomic nervous system seem intact in PD+NOH. © 2008 Movement Disorder Society     

Cardiac stress test is normal in pre‐motor Parkinson's disease

Cardiac sympathetic denervation is an early nonmotor feature of Parkinson's disease (PD). The aim of the current study was to trace evidence for cardiac dysfunction abnormalities in the premotor phase of PD. We retrospectively reviewed treadmill ergometric tests of a large cohort (n = 16,841) between 2000 and 2012, that attended the Executive Screening Survey (ESS) at Sheba Medical Center. Heart rate and blood pressure profiles as well as exercise capacity were compared between subjects who later developed PD and age‐ and sex‐matched subjects (ratio 1:2) who did not. We identified 28 subjects (24 males) who developed PD at follow‐up. The PD group was older than the group of subjects who did not develop PD on first ergometric test (64.82 ± 8.82 vs. 48.91 ± 10.60 years, P < 0.001). The time between the first ergometric test and motor symptoms onset was 4.64 ± 2.86 years. Patients who later developed PD had lower maximal heart rate (P < 0.001) and lower heart rate reserve than healthy controls (P < 0.001); however, compared with age‐ and sex‐matched subjects, subjects who developed PD had similar exercise capacity and heart rate profile during rest, exercise, and recovery, even 1 year before diagnosis. In this study, we did not detect significant signs of sympathetic dysfunction during the premotor phase of PD. © 2014 International Parkinson and Movement Disorder Society     

Health‐related quality of life in early Parkinson's disease: The impact of nonmotor symptoms

Nonmotor symptoms (NMS) are common in patients with established Parkinson's disease (PD) and have a major impact upon quality of life. We investigated the significance of NMS in relation to health‐related quality of life (HRQoL) in patients with newly diagnosed PD. Patients and healthy controls were recruited as part of the Incidence of Cognitive Impairment in Cohorts with Longitudinal Evaluation in Parkinson's Disease Study. Prevalence of NMS was determined with the Non‐Motor Symptom Questionnaire. HRQoL was recorded with the 39‐item Parkinson's Disease Quality of Life Questionnaire (PDQ‐39). Further assessments included measures of motor disability, depression, sleep, and cognition. One hundred and fifty‐eight patients with newly diagnosed PD and 99 controls participated in this cross‐sectional study. Patients reported greater numbers of NMS than controls (mean 8.3 ± 4.3 versus 2.8 ± 2.5 symptoms; P < 0.001). Patients reported lowest HRQoL in the domains assessing bodily discomfort, mobility, and activities of daily living. Motor and nonmotor symptoms impacted negatively upon HRQoL scores. Patients with the postural instability and gait difficulty motor subtype reported worse HRQoL, compared with those with tremor‐dominant disease. Depression (P < 0.001), incomplete bowel emptying (P < 0.001), anxiety (P < 0.001), impaired concentration (P < 0.001), memory complaints (P < 0.001), and insomnia (P = 0.001) had the greatest negative impact upon HRQoL. NMS are common in patients with early PD and represent a significant cause of poorer health‐related quality of life. Cognitive, neuropsychiatric, and sleep disturbances are particularly associated with reduced well‐being. Screening and management of these symptoms should be prioritized at the time of diagnosis. © 2013 International Parkinson and Movement Disorder Society     

Pupillary supersensitivity and visual disturbance in Parkinson’s disease

This study evaluated pupillary postganglionic autonomic dysfunction and its relationship to visual disturbance in idiopathic Parkinson’s disease (PD). Pupillary sensitivity was examined in relation to a parasympathomimetic agent [0.05% pilocarpine hydrochloride (PL)] and to a sympathomimetic agent [0.02% dipivefrine hydrochloride (DPE)] using infrared pupillography in 40 PD patients and 17 age-matched controls. Visual disturbances were evaluated as well, including blurring, photophobia, night blindness and involuntary eyelid closure in response to light. Pupillary supersensitivity to PL and DPE and their relation to visual disturbances were found to be significantly greater in PD patients than in controls (22.3 ± 15.1 vs. 10.4 ± 11.4%, P < 0.005, and14.5 ± 14.5 vs. 4.9 ± 8.7%, P < 0.01, respectively). In addition, pupillary sympathetic supersensitivity did not correlate with a reduction of ¹²³I-metaiodobenzylguanidine (MIBG) cardiac accumulation. Patients with PD reported more blurred vision (P < 0.001) and involuntary eyelid closure in response to light (P < 0.05) than controls. Patients with supersensitivity to both PL and DPE complained more often of blurred vision than patients without supersensitivity (P < 0.05). Pupillary sensitivity to PL correlated significantly with a summed score for visual disturbance (P < 0.05, r = 0.417), but DPE sensitivity did not. PD patients have both parasympathetic and sympathetic postganglionic impairments affecting the pupil. Our findings demonstrate that parasympathetic dysfunction contributes significantly to visual disturbance in PD.     

Parkinson's disease tremor is diminished with relaxation guided imagery

Patients with Parkinson's disease (PD) may have pronounced tremor that exacerbates during stress. To determine whether PD tremor improves with relaxation guided imagery (RGI) and relaxing music. Twenty patients with PD with moderate to severe tremor participated in sessions where relaxation techniques were implemented. Tremor was objectively monitored using an accelerometer. RGI dramatically decreased tremor in all 20 patients (baseline 270.38 ± 85.82 vs. RGI 35.57 ± 43.90 movements per minute P < 0.0001). In 15 patients, RGI completely abolished tremor for 1–13 min. Average tremor activity remained significantly bellow baseline both 15 min and 30 min after RGI was discontinued (P < 0.001). Patients reported improvement lasting 2–14 hours (mean 6.8 ± 3.8). Relaxing music significantly reduced tremor but to a lesser degree than RGI (220.04 ± 106.53 movements per minute P = 0.01). Self‐relaxation had no significant effect on tremor. RGI can supplement conventional medical treatments for tremor in patients with PD on best medical treatment. © 2009 Movement Disorder Society     

Four‐week trunk‐specific rehabilitation treatment improves lateral trunk flexion in Parkinson's disease

People with Parkinson's disease (PD) often have a posture characterized by lateral trunk flexion poorly responsive to antiparkinsonian drugs. To examine the effects of a rehabilitation programme (daily individual 90‐minute‐sessions, 5‐days‐a‐week for 4‐consecutive weeks) on lateral trunk flexion and mobility, 22 PD patients with mild to severe lateral trunk flexion, and 22 PD patients without trunk flexion were studied. Patients were evaluated using the Unified Parkinson's Disease Rating Scale motor subscale (UPDRS‐III) score, and the kinematic behavior of the trunk was recorded by means of an optoelectronic system to determine: a) trunk flexion, inclination and rotation values in the erect standing posture; b) ranges of trunk flexion and inclination during trunk movements. After the treatment, significant decreases in trunk flexion [24°(4) vs. 14°(3), P < 0.001] and inclination in the static condition [23°(5) vs. 12°(4), P < 0.001)] were observed, both of which were maintained at the 6‐month follow up. During the trunk flexion task, a significantly increased range of trunk flexion [64°(15) vs. 83°(15), P < 0.001] was observed; similarly, during the lateral bending task, the range of trunk inclination was found to be significantly increased, both toward the side of the trunk deviation [29°(8) vs. 42°(13), P < 0.01] and toward the contralateral side [14°(6) vs 29°(11), P < 0.01]. No further significant changes were observed at the 6‐month follow‐up. Trunk flexion and inclination values in the upright standing posture correlated slightly with the UPDRS‐III score. Our findings show that significant improvements in axial posture and trunk mobility can be obtained through the 4‐week rehabilitation programme described, with a parallel improvement in clinical status. © 2010 Movement Disorder Society     

One‐year follow‐up study of neuropathic pain in chronic inflammatory demyelinating polyradiculoneuropathy

We sought to gather information about frequency and features of neuropathic pain (NeP) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) patients and to investigate course of NeP during 1‐year follow‐up. Study included 105 patients diagnosed with CIDP. Patients with diabetes (N = 26) were excluded. NeP was diagnosed by the official guidelines and painDETECT questionnaire (PD‐Q). Medical Research Council Sum Score (MRC‐SS), INCAT disability and sensory scores, and Beck Depression Inventory were also measured. PD‐Q showed presence of NeP in 16 (20%) of 79 CIDP patients and their mean pain was moderate (5.1 ± 3.0 of 10). Diagnostic delay in CIDP patients with NeP was prolonged compared to CIDP patients without NeP (21 ± 28 vs 9 ± 12 months, P < .05). Slowly progressive course of the disease was more frequent in patients with NeP (81% vs 52%, P < .05). Patients with NeP had worse INCAT sensory score (P < .01), INCAT disability score (P < .05), MRC‐SS, as well as worse disease outcome at time of testing (P < .05). Depression was more common in patients with NeP (69% vs 17%, P < .01). During 1‐year follow‐up, majority of our CIDP patients had good control of NeP with gabapentinoids or amitriptyline. NeP was common in our cohort of non‐diabetic CIDP patients. It was associated with worse functional disability, worse sensory deficit, and depression. Special attention should be paid to CIDP patients with NeP because they request additional symptomatic therapy that appeared efficacious in our cohort.     

Subclinical pulmonary dysfunction in spinocerebellar ataxias 1, 2 and 3

Sriranjini SJ, Pal PK, Krishna N, Sathyaprabha TN. Subclinical pulmonary dysfunction in spinocerebellar ataxias 1, 2 and 3. Acta Neurol Scand: 2010: 122: 323–328. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objectives – Evaluation of pulmonary function in patients with spinocerebellar ataxias (SCA) 1, 2 and 3 without clinical evidence of pulmonary dysfunction. Methods – Thirty patients (F:M = 7:23; age: 35 ± 11.3 years; SCA1 – 13, SCA2 – 9 and SCA3 – 8) without clinical manifestations of respiratory dysfunction and 30 controls underwent pulmonary function tests. The percentage predicted values of forced vital capacity (FVC), volume of air exhaled during first second of FVC (FEV1), peak expiratory flow rate (PEFR) and maximal voluntary ventilation (MVV), actual values of maximal inspiratory and expiratory pressures (MIP and MEP in mmHg), and ratios of actual values of FEV1/FVC (%) and FEV1/PEFR (ml/l/min) were analyzed. Results – Compared with controls SCA patients had significant reductions of FVC (71.1 ± 17.5 vs 85.5 ± 18.7; P < 0.01), PEFR (51.5 ± 20.7 vs 77.1 ± 24.9; P < 0.001), MVV (64.4 ± 21.6 vs 97.2 ± 22.7; P < 0.001), MIP (27.7 ± 16.8 vs 50.1 ± 15.1; P < 0.001) and MEP (38.1 ± 18.7 vs 74.7 ± 16.0; P < 0.001), elevation of FEV1/PEFR (10.5 ± 2.8 vs 7.4 ± 2.1; P < 0.001), but no significant change of FEV1 and FEV1/FVC. FEV1/PEFR correlated positively with illness duration and MVV negatively with severity of illness. Conclusions – The present study showed subclinical restrictive type of pulmonary dysfunction in SCA, and possible presence of upper airway obstruction. Chest physiotherapy and breathing exercises should be introduced early in management of SCA.     

Impaired finger dexterity in patients with parkinson's disease correlates with discriminative cutaneous sensory dysfunction

To study the influence of discriminative cutaneous sensory dysfunction on impaired finger dexterity in Parkinson's disease (PD), we evaluated 48 right‐handed PD patients during a practically defined off‐medication period and 24 healthy age‐matched controls. With visual deprivation, a finger tapping task (FTT) was performed to assess the speed of simple repetitive finger movements and a coin rotation task (CRT) was used to assess finger dexterity. The tasks were performed with the right hand. We measured the somesthetic temporal discrimination threshold (sTDT) in the right index finger. The mean ± SD FTT score of the patient group was lower than that of the control group (24.0 ± 8.0 vs. 29.8 ± 7.8; P < 0.01). The patient group performed worse on the CRT than the control group (8.5 ± 3.5 vs. 12.6 ± 1.7; P < 0.001). The mean sTDT value of the patient group was longer than that of the control group (124.0 ± 44.8 vs. 78.1 ± 26.2 ms; P < 0.001). The CRT scores correlated with the sTDT values (Pearson's correlation coefficient = ?0.43; P < 0.01), but not with the Unified Parkinson's Disease Rating Scale (UPDRS) finger bradykinesia scores or FTT scores. Multiple regression analysis showed that the sTDT values (parameter estimate = ?0.03, SE = 0.01; P < 0.01), but not patient age, UPDRS finger bradykinesia score, or FTT score, affected the CRT score. Slowness of simple repetitive finger movements did not have a strong impact on the impaired manual dexterity of PD. Discriminative sensory dysfunction and consequent abnormal sensorimotor integration seem to be involved in the impaired finger dexterity of PD. © 2010 Movement Disorder Society.     

Cardiac sympathetic denervation correlates with clinical and pathologic stages of Parkinson's disease

Attention has been drawn to cardiac sympathetic denervation in Parkinson's disease (PD) based on clinical studies using [123I] metaiodobenzylguanidine scintigraphy; however, the histologic correlates and time course of cardiac sympathetic denervation are poorly understood. To address these issues, we used tyrosine hydroxylase (TH) immunohistochemistry to detect cardiac sympathetic nerve fibers in the epicardium of 4 normal controls, 11 cases with incidental Lewy bodies (iLBs), and 14 cases of PD. Cardiac sympathetic innervation was significantly less in PD than in normal controls and cases with iLBs (P < 0.05). There was also a decrease in TH‐immunoreactive fibers in iLB cases compared to normal controls (P < 0.01). TH‐immunoreactive fibers correlated with the PD stage (r = ?0.75, P < 0.001), as well as with Hoehn & Yahr clinical stage (r = ?0.61, P < 0.001), and disease duration (r = ?0.63, P < 0.001). Immunohistochemistry for α‐synuclein showed neurites in epicardium in PD and iLB cases, but not in normal controls. The density of α‐synuclein neurites correlated with Braak PD stage (r = 0.38, P < 0.05), Hoehn & Yahr clinical stage (r = 0.44, P < 0.05), and disease duration (r = 0.42, P < 0.05). This study demonstrates that cardiac sympathetic degeneration and α‐synuclein pathology is present in presymptomatic phase of PD, and that both increase with disease duration and severity. © 2008 Movement Disorder Society.     

Poor dopaminergic response of impaired dexterity in Parkinson's disease: Bradykinesia or limb kinetic apraxia?

Patients with Parkinson's disease (PD) often show impaired manual dexterity even when being only minimally bradykinetic, suggesting that they may have limb kinetic apraxia (LKA), that is, a loss of fine motor skill not explained by elemental motor deficits. To explore this dissociation, we investigated the differential dopaminergic responsiveness of dexterity and bradykinesia in PD. Twelve patients with PD (4 women, age 64.4 ± 8.3, mean + SD) and 12 matched healthy controls (64.8 ± 8.9) were tested twice in ON vs. OFF and 1st vs. 2nd trial, respectively. A coin rotation (CR) task was applied to assess dexterity and a finger tapping (FT) task to assess bradykinesia. Performance was followed by video recording and analyzed by measuring the frequency of CR and FT during three 10‐second periods. Statistical analysis was done by a mixed factorial design with group (PD vs. controls) as between‐subject factor and medication (ON‐ vs. OFF‐state or 1st vs. 2nd trial), task (FT vs. CR), and handedness (dominant vs. nondominant) as within‐subject factors. In patients with PD, regardless of hand involved, dopaminergic treatment only mildly improved CR performance, in contrast to the strong increase in FT scores (up to the level of controls), as demonstrated by the significant triple interaction of the factors group, medication, and task (F_1,22 = 7.9, P = 0.01; η² = 0.26). Furthermore, CR scores were considerably lower, both in OFF and ON, than in normal controls, pointing to a substantial impairment of dexterity in PD (P < 0.001). In conclusion, impaired manual dexterity showing significantly diminished response to dopaminergic treatment suggests that dextrous deficits in PD are related to LKA rather than bradykinesia. © 2008 Movement Disorder Society     

Non-motor features in essential tremor

Introduction – Essential tremor (ET) is increasingly recognized to have several non‐motor manifestations. The aim of this study was to determine the prevalence of non‐motor manifestations in ET and its impact on the quality of life (QOL). Methods – This was a cross‐sectional case–control questionnaire‐based study. The subjects were 50 patients with ET and 50 matched healthy controls. All subjects were assessed by Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Parkinson Fatigue Scale, Brief Pain Inventory, Hamilton Anxiety Rating Scale, and Hamilton Depression Rating Scale. In addition, QOL in Essential Tremor questionnaire was administered to patients with ET. Results – Patients with ET, when compared with controls, had significantly higher prevalence and higher mean scores of sleep disturbances (46% vs 8%, P < 0.001; 5.9 ± 4.6 vs 2.6 ± 2.3, P < 0.001), fatigue (30% vs 8%, P = 0.009; 5.8 ± 0.8 vs 2.5 ± 0.4, P < 0.001), anxiety (66% vs 18%, P = 0.009; 7.4 ± 9.0 vs 0.7 ± 2.6, P < 0.001), depression (44% vs 8%, P = 0.009; 7.8 ± 7.9 vs 1.7 ± 3.3, P < 0.001) as well as higher mean score of pain severity (1.9 ± 2.3 vs 0.6 ± 1.2, P = 0.001) and interference owing to pain (2.0 ± 2.9 vs 0.5 ± 1.2, P = 0.001). Following hierarchical regression analysis, depression was the only non‐motor feature that affected the QOL. Conclusion – There was a significantly higher prevalence and greater severity of sleep disturbances, fatigue, pain, anxiety, and depression in patients with ET and depression significantly affected the QOL.     

Mild Parkinsonian signs are associated with lower olfactory test scores in the community‐dwelling elderly

Mild Parkinsonian signs (MPS, impaired gait, rigidity, bradykinesia, rest tremor) are commonly found during the clinical examination of older people and may be a precursor to Parkinson's disease (PD) or Alzheimer's disease (AD). Marked deficits in olfaction occur in PD and AD. The objective of this study was to determine whether University of Pennsylvania Smell Test (UPSIT) scores were lower in nondemented community‐dwelling elderly with versus without MPS. Nondemented persons age ≥65 years without PD in Washington Heights‐Inwood, NY were evaluated with an abbreviated motor Unified PD Rating Scale and a 40‐item UPSIT. Lower UPSIT and higher transformed UPSIT score (square root [UPSIT ‐ 41]) indicated greater olfactory dysfunction. One‐hundred‐seventy‐seven (16.4%) of 1,078 participants had MPS. Mean UPSIT scores (MPS vs. without MPS) were 24.3 ± 7.1 versus 26.4 ± 6.8, P < 0.001. In a logistic regression analysis adjusting for age and education, transformed UPSIT score was associated with MPS (OR 1.25, 95% CI 1.04–1.52, P = 0.02). In an adjusted logistic regression analysis, participants with higher transformed UPSIT scores (based on a median split) were 1.55 times more likely to have MPS than were those with lower scores (P = 0.01). Within transformed UPSIT score quartiles, the odds of having MPS were 1.0 (reference), 1.35, 2.02, and 2.20 (P < 0.05). The association with transformed UPSIT scores was similar across MPS subtypes (axial dysfunction, rigidity, tremor).MPS were associated with a mild reduction in olfactory function. These observations further support the view of MPS as a marker of emerging degenerative brain pathologies. © 2007 Movement Disorder Society     

Long‐term clinical outcome in meige syndrome treated with internal pallidum deep brain stimulation

Deep brain stimulation of the globus pallidus internus (GPi DBS) is effective in the treatment of primary segmental and generalized dystonia. Although limb, neck, or truncal dystonia are markedly improved, orofacial dystonia is ameliorated to a lesser extent. Nevertheless, several case reports and small cohort studies have described favorable short‐term results of GPi DBS in patients with severe Meige syndrome. Here, we extend this preliminary experience by reporting long‐term outcome in a multicenter case series, following 12 patients (6 women, 6 men) with Meige syndrome for up to 78 months after bilateral GPi DBS. We retrospectively assessed dystonia severity based on preoperative and postoperative video documentation. Mean age of patients at surgery was 64.5 ± 4.4 years, and mean disease duration 8.3 ± 4.4 years. Dystonia severity as assessed by the Burke–Fahn–Marsden Dystonia Rating Scale showed a mean improvement of 45% at short‐term follow‐up (4.4 ± 1.5 months; P < 0.001) and of 53% at long‐term follow‐up (38.8 ± 21.7 months; P < 0.001). Subscores for eyes were improved by 38% (P = 0.004) and 47% (P < 0.001), for mouth by 50% (P < 0.001) and 56% (P < 0.001), and for speech/swallowing by 44% (P = 0.058) and 64% (P = 0.004). Mean improvements were 25% (P = 0.006) and 38% (P < 0.001) on the Blepharospasm Movement Scale and 44% (P < 0.001) and 49% (P < 0.001) on the Abnormal Involuntary Movement Scale. This series, which is the first to demonstrate a long‐term follow‐up in a large number of patients, shows that GPi DBS is a safe and highly effective therapy for Meige syndrome. The benefit is preserved for up to 6 years. © 2011 Movement Disorder Society     

Apparent diffusion coefficient of the superior cerebellar peduncle differentiates progressive supranuclear palsy from Parkinson's disease

The early diagnosis of progressive supranuclear palsy (PSP) may be challenging, because of clinical overlapping features with Parkinson's disease (PD) and other parkinsonian syndromes such as the Parkinsonian variant of multiple system atrophy (MSA‐P). Conventional MRI can help in differentiating parkinsonian disorders but its diagnostic accuracy is still unsatisfactory. On the basis of the pathological demonstration of superior cerebellar peduncle (SCP) atrophy in patients with PSP, we assessed the SCP apparent diffusion coefficient (ADC) values in patients with PSP, PD, and MSA‐P in order to evaluate its differential diagnostic value in vivo. Twenty‐eight patients with PSP (14 with possible‐PSP and 14 with probable‐PSP), 15 PD, 15 MSA‐P, and 16 healthy subjects were studied by using diffusion weighted imaging (DWI). ADC was calculated in regions of interest defined in the left and right SCP by two clinically blinded operators. Intrarater (r = 0.98, P < 0.001) and interrater reliability (r = 0.97; P < 0.001) for SCP measurements were high. Patients with PSP had higher SCP rADC values (median 0.98 × 10^?3mm²/s) than patients with PD (median 0.79 × 10^?3 mm²/s, P < 0.001), MSA‐P (median 0.79 × 10^?3 mm²/s, P < 0.001), and healthy controls (median 0.80 × 10^?3 mm²/s, P < 0.001). DWI discriminated patients with PSP from PD and healthy subjects on the basis of SCP rADC individual values (100% sensitivity and specificity) and from patients with MSA‐P (96.4% sensitivity and 93.3% specificity). The higher values of rADC in SCP of patients with PSP correspond with the in vivo microstructural feature of atrophy detected postmortem and provide an additional support for early discrimination between PSP and other neurodegenerative parkinsonisms. © 2008 Movement Disorder Society     

Altered ceramide acyl chain length and ceramide synthase gene expression in Parkinson's disease

Genetic studies have provided increasing evidence that ceramide homeostasis plays a role in neurodegenerative diseases including Parkinson's disease (PD). It is known that the relative amounts of different ceramide molecular species, as defined by their fatty acyl chain length, regulate ceramide function in lipid membranes and in signaling pathways. In the present study we used a comprehensive sphingolipidomic case‐control approach to determine the effects of PD on ceramide composition in postmortem brain tissue from the anterior cingulate cortex (a region with significant PD pathology) and the occipital cortex (spared in PD), also assessing mRNA expression of the major ceramide synthase genes that regulate ceramide acyl chain composition in the same tissue using quantitative PCR. In PD anterior cingulate cortex but not occipital cortex, total ceramide and sphingomyelin levels were reduced from control levels by 53% (P < 0.001) and 42% (P < 0.001), respectively. Of the 13 ceramide and 15 sphingomyelin molecular lipid species identified and quantified, there was a significant shift in the ceramide acyl chain composition toward shorter acyl chain length in the PD anterior cingulate cortex. This PD‐associated change in ceramide acyl chain composition was accompanied by an upregulation of ceramide synthase‐1 gene expression, which we consider may represent a response to reduced ceramide levels. These data suggest a significant shift in ceramide function in lipid membranes and signaling pathways occurs in regions with PD pathology. Identifying the regulatory mechanisms precipitating this change may provide novel targets for future therapeutics. © 2013 International Parkinson and Movement Disorder Society     

Frailty in elderly persons with essential tremor: a population‐based study (NEDICES)

Background and purpose: Essential tremor (ET), one of the most prevalent neurological diseases, has been associated with a variety of comorbidities and, in some studies, a modest increase in risk of mortality. The mechanisms underlying this possible increased mortality have yet to be explored, although one possibility is increased frailty. Frailty has not been studied in ET, and our objective was to address this gap in knowledge. We hypothesized that frailty would be greater in ET cases than in controls. Methods: A 20‐item frailty score assessed comorbid conditions, number of medications, and functional activity. The frailty score was compared in 237 non‐demented elderly ET cases and 3903 non‐demented age‐matched controls from a population‐based study in central Spain. Results: The frailty score was higher in ET cases than in controls (8.6 ± 5.2 vs. 6.8 ± 4.6, P < 0.001). Stratifying the frailty score into quartiles and tertiles similarly revealed case–control differences (both P < 0.001). The frailty score also increased with age (r = 0.25, P < 0.001), was higher in women than men (P = 0.02), was correlated with subjective rating of health status (r = 0.42, P < 0.001), and was inversely correlated with body weight (r = −0.06, P < 0.001) and hours/day that participants performed moderate or intensive physical activities (r = −0.16, P < 0.001). Conclusion: Essential tremor cases had increased frailty compared to their counterparts without this disease. Whether this increased frailty is a contributor to the increased risk of mortality that has been observed in some studies is a question that deserves further scrutiny.     

Effect of MTHFR Polymorphisms on Hyperhomocysteinemia in Levodopa-treated Parkinsonian Patients

High plasma homocysteine levels have been observed in Parkinson’s disease (PD) patients treated with levodopa. In this study, we investigated the effects of C677T and A1298C MTHFR polymorphisms, in association with l-DOPA daily dose and vitamin status, on hyperhomocysteinemia development in PD patients. Plasma homocysteine and folate/vitamin B12 levels were assayed in 49 l-DOPA-treated PD patients, and compared with those of 86 healthy subjects. Genotyping for MTHFR polymorphisms was carried out by DG-DGGE. Homocysteine levels were significantly higher in patients than in controls (16.3 ± 5.7 vs. 11.7 ± 2.7 μmol/l, P < 0.01). No significant differences were found between patients and controls with regard to folate/vitamin B12 levels, and MTHFR allele distribution. The TT+AA genotype was significantly more frequent in PD patients than in controls (32.5% vs. 17.4%, P < 0.05), but not associated with an increased risk for PD (OR = 2.3, CI = 1.0–5.2). Further, patients carrier of this genotype exhibited a mild hyperhomocysteinemia (22.1 ± 4.9 μmol/l), while a protective effect was observed in patients having the CC+AA genotype (11.2 ± 1.6 μmol/l; OR = 0.19, CI = 0.06–0.59). Interestingly, homocysteine levels were also moderately increased in patients with CT heterozygous genotype, in the context of either AA or AC (14.5 ± 3.6 μmol/l), in comparison to subjects with the CC + AA genotype. Finally, we did not find any significant association of combined C677T and A1298C MTHFR polymorphisms with an increased risk for hyperhomocysteinemia in PD patients. A better understanding of the role of homocysteine and MTHFR genotypes in PD is needed to reveal novel approaches for disease management.