Factors to predict recurrence after epidural blood patch in patients with spontaneous intracranial hypotension.

OBJECTIVES: This study aimed to identify predictors for the recurrence of spontaneous intracranial hypotension (SIH) after epidural blood patch (EBP). BACKGROUND: Epidural blood patch is the main treatment option for SIH; however, the characteristics of patients who experience relapse after successful EBP treatment for SIH remain understudied. METHODS: In this exploratory, retrospective, case-control study, we included 19 patients with SIH recurrence after EBP and 36 age- and sex-matched patients without recurrence from a single tertiary medical institution. We analyzed clinical characteristics, neuroimaging findings, and volume changes in intracranial structures after EBP treatment. Machine learning methods were utilized to predict the recurrence of SIH after EBP treatment. RESULTS: There were no significant differences in clinical features between the recurrence and no-recurrence groups. Among brain magnetic resonance imaging signs, diffuse pachymeningeal enhancement and cerebral venous dilatation were more prominent in the recurrence group than no-recurrence group after EBP (14/19 [73%] vs. eight of 36 [22%] patients, p = 0.001; 11/19 [57%] vs. seven of 36 [19%] patients, p = 0.010, respectively). The midbrain-pons angle decreased in the recurrence group compared to the no-recurrence group after EBP, at a mean (standard deviation [SD]) of -12.0 [16.7] vs. +1.8[18.3]° (p = 0.048). In volumetric analysis, volume changes after EBP were smaller in the recurrence group than in the no-recurrence group in intracranial cerebrospinal fluid (mean [SD] -11.6 [15.3] vs. +4.8 [17.1] mL, p = 0.001) and ventricles (mean [SD] +1.0 [2.0] vs. +2.0 [2.5] mL, p = 0.003). Notably, the random forest classifier indicated that the model constructed with brain volumetry was more accurate in discriminating SIH recurrence (area under the curve = 0.80 vs. 0.52). CONCLUSION: Our study suggests that volumetric analysis of intracranial structures may aid in predicting recurrence after EBP treatment in patients with SIH.

Effect of high-frequency repetitive transcranial magnetic stimulation on major depressive disorder in patients with Parkinson's disease.

Major depressive disorder (MDD) occurs in a small proportion of patients with Parkinson's disease (PD) and reduces their quality of life. We performed a randomized sham-controlled study to evaluate the effect of high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) on MDD in patients with PD. Ten patients participated to a real-rTMS group and eight patients to a sham-rTMS group. Evaluations were performed at baseline, 2 and 6 weeks after rTMS treatment. All participants underwent examinations of depression rating scales, including the Hamilton Rating Scale, the Montgomery-Asberg Depression Rating Scale (MADRS), and the Beck Depression Inventory (BDI) and the motor part of the Unified Parkinson Disease Rating Scale (UPDRS-III). The real-rTMS group had improved scores on HRS and the MADRS after 10 sessions, and these beneficial effects persisted for 6 weeks after the initial session. The BDI score did not change immediately after the sessions. The sham-rTMS group had no significant changes in any of the depression rating scales. The UPDRS-III did not change in either group. HF-rTMS of the left DLPFC is an effective treatment for MDD in patients with PD.

Factors contributing to malnutrition in patients with Parkinson's disease.

Our objective in this study was to evaluate the nutritional status and to identify clinical, psychosocial, and nutritional factors contributing to malnutrition in Korean patients with Parkinson's disease. We used a descriptive, cross-sectional study design. Of 102 enrolled patients, 26 (25.5%) were malnourished and 27 (26.5%) were at risk of malnutrition based on Mini-Nutritional Assessment scores. Malnutrition was related to activity of daily living score, Hoehn and Yahr stage, duration of levodopa therapy, Beck Depression Inventory and Spielberger's Anxiety Inventory scores, body weight, body weight at onset of Parkinson's disease, and body mass index. On multiple logistic regression analysis, anxiety score, duration of levodopa therapy, body weight at onset of Parkinson's disease, and loss of body weight were significant factors predicting malnutrition in Parkinson's disease patients. Therefore, nutritional assessment, including psychological evaluation, is required for Parkinson's disease patients to facilitate interdisciplinary nutritional intervention for malnourished patients.

Large-scale assessment of polyglutamine repeat expansions in Parkinson disease.

OBJECTIVES: We aim to clarify the pathogenic role of intermediate size repeat expansions of SCA2, SCA3, SCA6, and SCA17 as risk factors for idiopathic Parkinson disease (PD). METHODS: We invited researchers from the Genetic Epidemiology of Parkinson's Disease Consortium to participate in the study. There were 12,346 cases and 8,164 controls genotyped, for a total of 4 repeats within the SCA2, SCA3, SCA6, and SCA17 genes. Fixed- and random-effects models were used to estimate the summary risk estimates for the genes. We investigated between-study heterogeneity and heterogeneity between different ethnic populations. RESULTS: We did not observe any definite pathogenic repeat expansions for SCA2, SCA3, SCA6, and SCA17 genes in patients with idiopathic PD from Caucasian and Asian populations. Furthermore, overall analysis did not reveal any significant association between intermediate repeats and PD. The effect estimates (odds ratio) ranged from 0.93 to 1.01 in the overall cohort for the SCA2, SCA3, SCA6, and SCA17 loci. CONCLUSIONS: Our study did not support a major role for definite pathogenic repeat expansions in SCA2, SCA3, SCA6, and SCA17 genes for idiopathic PD. Thus, results of this large study do not support diagnostic screening of SCA2, SCA3, SCA6, and SCA17 gene repeats in the common idiopathic form of PD. Likewise, this largest multicentered study performed to date excludes the role of intermediate repeats of these genes as a risk factor for PD.

Three-dimensional fluid-attenuated inversion recovery sequence for visualisation of subthalamic nucleus for deep brain stimulation in Parkinson's disease.

INTRODUCTION: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an accepted treatment for advanced Parkinson's disease (PD). However, targeting the STN is difficult due to its relatively small size and variable location. The purpose of this study was to assess which of the following sequences obtained with the 3.0 T MR system can accurately delineate the STN: coronal 3D fluid-attenuated inversion recovery (FLAIR), 2D T2*-weighted fast-field echo (T2*-FFE) and 2D T2-weighted turbo spin-echo (TSE) sequences. METHODS: We included 20 consecutive patients with PD who underwent 3.0 T MR for DBS targeting. 3D FLAIR, 2D T2*-FFE and T2-TSE images were obtained for all study patients. Image quality and demarcation of the STN were analysed using 4-point scales, and contrast ratio (CR) of the STN and normal white matter was calculated. The Friedman test was used to compare the three sequences. RESULTS: In qualitative analysis, the 2D T2*-FFE image showed more artefacts than 3D FLAIR or 2D T2-TSE, but the difference did not reach statistical significance. 3D FLAIR images showed significantly superior demarcation of the STN compared with 2D T2*-FFE and T2-TSE images (P < 0.001, respectively). The CR of 3D FLAIR was significantly higher than that of 2D T2*-FFE or T2-TSE images in multiple comparison correction (P < 0.001), but there was no significant difference in the CR between 2D T2*-FFE and T2-TSE images. CONCLUSION: Coronal 3D FLAIR images showed the most accurate demarcation of the STN for DBS targeting among coronal 3D FLAIR, 2D T2*-FFE and T2-TSE images.

The utility of susceptibility-weighted imaging for differentiating Parkinsonism-predominant multiple system atrophy from Parkinson's disease: correlation with 18F-flurodeoxyglucose positron-emission tomography.

Our study was intended to demonstrate the different signal intensity (SI) pattern of the putamen seen on susceptibility-weighted imaging (SWI) between that of Parkinson's disease (PD) and Parkinsonism-predominant multiple system atrophy (MSA-P), and to correlate it with (18)F-flurodeoxyglucose positron-emission tomography ((18)F-FDG PET). Thirty patients with PD and 17 with MSA-P underwent SWI, and (18)F-FDG PET were included. The SI was measured on SWI in the anterior and posterior halves of the putamen using a region-of-interest (ROI) on both sides. The normalized regional glucose metabolism (standardized uptake value ratio, SUVR) was measured on co-registered (18)F-FDG PET images using the ROI obtained with SWI. Analysis included a group-level comparison of the SI values obtained on SWI, and these results were correlated with the SUVR on (18)F-FDG PET. The SIs of the bilateral posterior, dominant-side of the posterior, mean values of the bilateral anterior and posterior halves of the putamen on SWI, differed significantly between the two groups (P < 0.001, respectively). The SUVR of the all locations also differed significantly between PD and MSA-P (P < 0.001, respectively). There was a moderate degree of positive correlation between the SI and the SUVR of the left posterior half, and mean value of the bilateral posterior putamen in MSA-P (r = 0.634, P = 0.006, r = 0.492, P = 0.045). In conclusion, the low SI seen on the posterior putamen may differentiate MSA-P from PD. Furthermore, low SI in the putamen correlated with hypometabolism on (18)F-FDG PET. Therefore, SWI could be a potential complementary diagnostic tool to (18)F-FDG PET for differentiating these conditions.

Emotional disturbance in CADASIL: its impact on quality of life and caregiver burden.

BACKGROUND AND PURPOSE: Recurrent strokes and cognitive dysfunction are the major symptoms of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). However, emotional disturbances in CADASIL patients are incompletely understood. The aim of this study was to investigate emotional disturbances in CADASIL and their impact on the patients' quality of life (QOL) and caregiver burden. METHODS: From 54 patients who were diagnosed as CADASIL between January 2000 and August 2012 in the Asan Medical Center, Seoul, Korea, 23 patients were enrolled in this study. The Montgomery-Asberg Depression Rating Scale was used for the assessment of depressive emotional disturbances (DED). For nondepressive emotional disturbances (NDED), the criteria of Kim and Choi-Kwon [Neurology 2000;54:1805-1810] were used for emotional incontinence (excessive/inappropriate expression of laughing or crying), and the modified Spielberger Trait Anger Scale was used for anger proneness (excessive/inappropriate expression of anger). Patients' QOL and caregiver burden were assessed with stroke-specific emotional QOL and the Sense of Competence Questionnaire (SCQ), respectively. Functional disability was assessed by the modified Rankin scale (mRS), and white matter ischemic changes and microbleeds were analyzed using brain magnetic resonance images. RESULTS: Twelve patients (52.2%) had various emotional disturbances including DED (n=10, 43.5%) and NDED (n=7, 30.4%). The presence of any emotional disturbances was associated with thalamic (p=0.012) and cortical (p=0.037) microbleeds, mRS (p=0.001), cognitive impairment (p=0.002), patients' low QOL (p=0.009) and increased caregiver burden (p=0.002). DED was associated with multiple (≥10) microbleeds (p=0.039), cognitive impairment (p=0.030) and mRS (p=0.030), and negatively influenced all domains of patients' QOL and caregiver burden. NDED was associated with cortical microbleeds (p=0.017) and mRS (p=0.014). Unlike DED, NDED was not associated with patients' poor QOL, except for thinking domain, but was significantly related to total SCQ and subscales 1 and 2 of SCQ (p=0.012). CONCLUSIONS: More than half the CADASIL patients had emotional disturbances, either DED or NDED. Both are associated with patients' poor QOL and increased caregiver burden, the former more markedly than the latter. Considering that CADASIL is a progressive disease with deteriorating patients' QOL, physicians have to pay more attention to emotional problems in CADASIL patients. Treatment strategies should be investigated in this regard to improve patients' QOL and reduce caregiver burden.

Alterations of mean diffusivity in brain white matter and deep gray matter in Parkinson's disease.

Although Parkinson's disease is a neurodegenerative disease primarily involving basal ganglia and midbrain, the deficit of white matter is also involved during the disease progression. As the diffusion tensor imaging method is sensitive to the microstructural changes, we investigated the microstructural alterations in white matter and deep gray matter in patients with Parkinson's disease. Brain images of 64 patients and sex- and age-matched 64 healthy controls were obtained from a 3T MRI scanner. Tract-based spatial statistics were used to compare the mean diffusivity of the white matter tract between the groups. Voxel-based analysis was used to compare the mean diffusivity of the subcortical gray matter between the groups. There were white matter deficits in the corticofugal tract, cingulum, uncinate fasciculus, crus of fornix or stria terminalis, corpus callosum, external capsule, superior longitudinal fasciculus, posterior thalamic radiation including optic radiation, and the tracts adjacent to the precuneus and supramarginal gyrus, as indicated by higher mean diffusivity in Parkinson's disease patients than in controls. There were also deficits in the left putamen, pallidum, thalamus, and caudate as indicated by higher mean diffusivity in Parkinson's disease patients than in controls. Using diffusion tensor imaging and multi-methods of image analysis, we successfully characterized and visualized brain white matter and deep gray matter areas with microstructural deficits in Parkinson's disease patients.

New perspective on parkinsonism in frontotemporal lobar degeneration.

Frontotemporal dementia (FTD) is the second most common type of presenile dementia. Three clinical prototypes have been defined; behavioral variant FTD, semantic dementia, and progressive nonfluent aphasia. Progressive supranuclear palsy, corticobasal degeneration, and motor neuron disease may possess clinical and pathological characteristics that overlap with FTD, and it is possible that they may all belong to the same clinicopathological spectrum. Frontotemporal lobar degeneration (FTLD) is a clinicopathological syndrome that encompasses a heterogenous group of neurodegenerative disorders. Owing to the advancement in the field of molecular genetics, diagnostic imaging, and pathology, FTLD has been the focus of great interest. Nevertheless, parkinsonism in FTLD has received relatively less attention. Parkinsonism is found in approximately 20-30% of patients in FTLD. Furthermore, parkinsonism can be seen in all FTLD subtypes, and some patients with familial and sporadic FTLD can present with prominent parkinsonism. Therefore, there is a need to understand parkinsonism in FTLD in order to obtain a better understanding of the disease. With regard to the clinical characteristics, the akinetic rigid type of parkinsonism has predominantly been described. Parkinsonism is frequently observed in familial FTD, more specifically, in FTD with parkinsonism linked to chromosome 17q (FTDP-17). The genes associated with parkinsonism are microtubule associated protein tau (MAPT), progranulin (GRN or PGRN), and chromosome 9 open reading frame 72 (C9ORF72) repeat expansion. The neural substrate of parkinsonism remains to be unveiled. Dopamine transporter (DAT) imaging revealed decreased uptake of DAT, and imaging findings indicated atrophic changes of the basal ganglia. Parkinsonism can be an important feature in FTLD and, therefore, increased attention is needed on the subject.

No effect of recumbency duration on the occurrence of post-lumbar puncture headache with a 22G cutting needle.

BACKGROUND: Supine recumbence has been widely performed to prevent post-lumbar puncture headache (PLPH). However, the optimal duration of supine recumbence is controversial. The aim of the study is to compare the occurrence of PLPH according to the duration of supine recumbence in patients with neurological disorders. METHODS: A non-equivalent control/experimental pre-/post-test study design was used. Seventy consecutive patients were prospectively enrolled between July 2007 and July 2008. Thirty-five patients underwent supine recumbence for four hours after lumbar puncture (Group 1) and 35 patients underwent supine recumbence for one hour (Group 2). RESULTS: The overall frequency of PLPH was 31.4%. The frequency of PLPH was not significantly different between the Group 1 (28.6%) and Group 2 (34.3%) (P = 0.607). In patients with PLPH, the median severity (P = 0.203) and median onset time of PLPH (P = 0.582) were not significantly different between the two groups. In a logistic regression analysis, the previous history of post-lumbar puncture headache was a significant risk factor for the occurrence of PLPH (OR = 11.250, 95% CI: 1.10-114.369, P = 0.041). CONCLUSIONS: Our study suggests that short duration (one hour) of supine recumbence may be as efficient as long duration (four hours) of supine recumbence to prevent PLPH.

Lateralized effects of unilateral thalamotomy and thalamic stimulation in patients with essential tremor.

BACKGROUND AND PURPOSE: Stereotactic thalamotomy has been an effective surgical procedure in the treatment of medically refractory essential tremor (ET), however, little is known about the bilateral effects of unilateral ventralis intermedius (Vim) thalamotomy and Vim deep brain stimulation (DBS). We studied the lateralized effects of unilateral Vim thalamotomy and Vim DBS in ET patients. METHODS: Vim thalamotomy was performed in 6 patients and Vim DBS in 6. Patients were evaluated preoperatively and at 3 and 6 months postoperatively using the Clinical Rating Scale for Tremor (CRST). RESULTS: The contralateral Part A (tremor localization/severity rating) and Part B (specific motor tasks/function rating) subscores, and axial subscores of CRST significantly improved after unilateral Vim thalamotomy or Vim DBS. On the side ipsilateral to surgery, ET patients demonstrated no significant improvements in the Part A and Part B subscores of CRST. The Part C (functional disabilities resulting from tremor) subscores and total scores of CRST were significantly improved after surgery. CONCLUSIONS: Vim thalamotomy and DBS may be equally effective for the management of contralateral and axial tremor in ET patients, but both interventions may not improve tremor on the side ipsilateral to surgery.

Levosulpiride-induced movement disorders.

Levosulpiride is a substituted benzamide that is widely used for the management of dyspepsia and emesis. However, little is known about levosulpiride-induced movement disorders (LIM). The aim of this study was to investigate the clinical characteristics of patients with LIM. Among 132 consecutive patients who were diagnosed with drug-induced movement disorders between January 2002 and March 2008, 91 patients with LIM were identified and their medical records reviewed. Seventy-eight (85.7%) patients were aged more than 60 years. The most common LIM was parkinsonism (LIP) (n = 85, 93.4%), followed by tardive dyskinesia (n = 9, 9.9%) and isolated tremor (n = 3, 3.3%). Twenty-one (24.7%) of the 85 patients with LIP were rated as Hoehn and Yahr stage III-V. The oro-lingual area was the only body part that was involved by tardive dyskinesia. LIM persisted after withdrawal of levosulpiride in 48.1% of patients with LIP, 66.7% with dyskinesia, and none with isolated tremor. None of clinical and MRI features predicted the reversibility of LIP. Levosulpiride frequently causes drug-induced movement disorders, presenting mainly with LIP followed by lower face dyskinesia. The symptoms are often severe, and irreversible even after the withdrawal of levosulpiride. Physicians should be cautious in using levosulpiride, especially in elderly patients.

Use of complementary and alternative medicine by Korean patients with Parkinson's disease.

OBJECTIVES: Many patients with Parkinson's disease (PD) often utilize complementary and alternative medicine (CAM). We aimed to survey the prevalence, spectrum of use, and factors related to utilization of CAM in patients with PD in Korea. PATIENTS AND METHODS: Between 15 December 2005 and 30 April 2006, we studied 123 patients with PD who volunteered to be interviewed using semi-structured questionnaires. RESULTS: Ninety-four (76%) patients had used CAM. The mean cost of CAM paid by patients (out-of-pocket costs) was 102.3 US Dollars (USD) per month, while medical costs of treatment for PD paid by patients (out-of-pocket costs) averaged 72.8 USD per month. Patients using CAM sought to improve motor symptoms (57.6%), fatigue (19.6%), pain (4.3%), constipation (5.4%) or specified no single reason (13.0%). The spectrum of CAM use included oriental medicines (76.6%), traditional food (44.7%), non-prescribed drugs (31.9%), traditional therapies (7.4%), massage (7.4%) and behavioral therapy (7.4%). Factors related to current use of CAM were disease duration, degree of education, and daily levodopa equivalent dose. In a logistic regression analysis, the duration of PD was a significant factor for CAM use. CONCLUSIONS: These results suggest that a high proportion of Korean PD patients employed CAM, associated with high costs and serious side effects in some patients.

Functional brain imaging in pure akinesia with gait freezing: [18F] FDG PET and [18F] FP-CIT PET analyses.

Pure akinesia with gait freezing (PAGF) has characteristic features, including freezing of gait and prominent speech disturbance without rigidity or tremor. The purpose of this study was to investigate changes in brain glucose metabolism and presynaptic dopaminergic function in PAGF. By using [(18)F] fluorodeoxyglucose (FDG) PET, 11 patients with PAGF were compared with 14 patients with probable progressive supranuclear palsy (PSP), 13 patients with Parkinson's disease (PD), and 11 normal controls. [(18)F] N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane (FP-CIT) PET was performed in 11 patients with PAGF and with 10 normal controls. The PAGF patients showed decreased glucose metabolism in the midbrain when compared with normal controls. PSP patients showed a similar topographic distribution of glucose hypometabolism with additional areas, including the frontal cortex, when compared with normal controls. The FP-CIT PET findings in patients with PAGF revealed severely decreased uptake bilaterally in the basal ganglia. These findings suggest that both PAGF and PSP may be part of the same pathophysiologic spectrum of disease. However, the reason why PAGF manifests clinically in a different manner needs to be further elucidated.

Effect of thalamotomy on focal hand dystonia in a family with DYT1 mutation.

We report the clinical and molecular features of a family with focal hand dystonia caused by DYT1 mutation. Four members of a family who underwent thalamotomy showed a marked and sustained therapeutic benefit that lasted for up to 12 years without recurrence of dystonia or any significant surgical complication. The hand dystonia caused by DYT1 mutation may be successfully managed by thalamotomy.