Yoon-Sang Oh

Association of cognitive dysfunction with neurocirculatory abnormalities in early Parkinson disease

Objective: Cognitive impairment and neurocirculatory abnormalities such as orthostatic hypotension (OH), supine hypertension (SH), and failure to decrease blood pressure at night (nondipping) occur relatively commonly in Parkinson disease (PD); however, whether cognitive dysfunction in early PD is related to neurocirculatory abnormalities has not been established. Cognitive dysfunction in PD is associated with white matter hyperintensities on MRI. We report results of an analysis of neuropsychological and hemodynamic parameters in patients with early PD. Methods: Among 87 patients, 25 had normal cognition, 48 had mild cognitive impairment, and 14 had dementia, based on comprehensive neuropsychological tests. Orthostatic vital signs and ambulatory 24-hour blood pressure monitoring were recorded, and brain magnetic resonance scans were obtained for all patients. Results: Cognitive impairment was associated with OH, SH, and white matter hyperintensities but not with nondipping. Dementia and white matter hyperintensities were common in SH. Of 13 patients with OH + SH, every one had mild cognitive impairment or dementia. Conclusions: Cognitive dysfunction is related to neurocirculatory abnormalities, especially OH + SH, in early PD, raising the possibility that early detection and effective treatment of those abnormalities might slow the rate of cognitive decline.

Cognitive improvement after long-term electrical stimulation of bilateral anterior thalamic nucleus in refractory epilepsy patients

INTRODUCTION The cognitive and behavioral effect of deep brain stimulation (DBS) administered to the deep cerebral nuclei for epilepsy treatment is unknown. We investigated the cognitive outcomes at least 12 months after DBS to the bilateral anterior thalamic nucleus (ATN) for controlling intractable epilepsy. METHODS Nine patients with intractable epilepsy who were not candidates for resective surgery, but who were treated by bilateral ATN DBS underwent cognitive and behavioral assessments before implantation and more than 1 year after DBS surgery. Postoperative cognitive assessments were carried out under a continuous stimulation mode. RESULTS The mean seizure-reduction rate of these patients after ATN DBS was 57.9% (35.6-90.4%). Cognitive testing showed favorable results for verbal fluency tasks (letter and category, p<0.05), and a significant improvement in delayed verbal memory was observed (p=0.017). However, we did not observe any significant changes in general abilities (IQ, MMSE), information processing (digit forward and backward, Trail A, and Digit Symbol), or executive function (Trail B and WCST). Interestingly, we did not observe any significant cognitive decline approximately 1 year (mean, 15.9 months) after ATN DBS surgery. CONCLUSIONS We showed that ATN DBS not only resulted in promising clinical effects but was also associated with improvements in both verbal recall and oral information processing, which may be related to the bilateral activation of the fronto-limbic circuit following DBS surgery. Further controlled, long-term studies with larger populations are warranted for elucidating the clinical effects of ATN DBS.

Nighttime Blood Pressure and White Matter Hyperintensities in Patients With Parkinson Disease

Increasing evidence indicates that nocturnal blood pressure level and/or loss of nocturnal blood pressure dips are sensitive markers of cardiovascular morbidity and mortality. Several studies have suggested that blunted heart rate variability and nocturnal decline in heart rate are also associated with target organ damage. These phenomena occur relatively commonly in patients with Parkinson disease (PD); however, few studies have assessed the consequences of these abnormalities in patients with PD. We investigated the influence of circadian changes in blood pressure and heart rate on white matter hyperintensities (WMHs) in patients with PD. The presence of nocturnal hypertension was associated with increased WMH score, and nighttime systolic pressure was closely related with white matter changes. Blunted heart rate variability and nocturnal decline in heart rate were also related to increasing WMH scores. The non-dipping phenomenon did not influence WMHs. These findings suggest that white matter changes are related to circadian autonomic dysfunction, particularly nocturnal hypertension in patients with PD. Therefore, it is important to monitor nocturnal blood pressure status, because modifying these circadian regulatory disturbances can be beneficial to protect against vascular brain damage in patients with PD. (Author correspondence: neuronet@catholic.ac.kr)

Incidental Unruptured Intracranial Aneurysms in Patients with Acute Ischemic Stroke

Background: The management and clinical prognosis of incidental intracranial aneurysms in acute ischemic stroke patients have been understudied. We investigated the clinical outcome of acute ischemic stroke subjects with incidentally found intracranial aneurysms. Methods: We consecutively included acute ischemic stroke patients within 7 days of onset. Their demographics, risk factors, stroke subtypes, antithrombotics use and modified Rankin scale (mRS) at 3 months after stroke were obtained. CT or MR angiography was used to diagnose the intracranial aneurysms. The development of an aneurysmal rupture was checked during the following 3 months. Results: Incidental intracranial aneurysms were found in 17 (6.6%) of the 258 patients. The female sex and old age were associated with the presence of incidental intracranial aneurysms (p = 0.001, 0.032). The most common site of aneurysm was at the distal internal carotid artery (n = 9), followed by the middle cerebral artery (n = 6). The diameters of the aneurysms ranged from 2.09 to 8.06 mm. All the participants except 1 who had cancer were taking antiplatelet agents. No aneurysmal rupture or subarachnoid hemorrhage happened until 3 months after stroke.There was no significant difference in excellent outcome (3-month mRS = 0, 1) between the patients with an aneurysm and those without (28.6 vs. 53.4%, p = 0.097). Conclusion: There was no rupture of the incidentally found aneurysms in the patients with acute ischemic stroke during their first 3 months. The 3-month mRS was not affected by the presence of incidental intracranial aneurysm. A large cohort study and long-term follow-up are required.

Combined use of 123I-metaiodobenzylguanidine (MIBG) scintigraphy and dopamine transporter (DAT) positron emission tomography (PET) predicts prognosis in drug-induced Parkinsonism (DIP): A 2-year follow-up study

DIP is a heterogeneous clinical syndrome; some patients develop persistent and worsening of parkinsonian symptoms after discontinuation of the offending drug, or Parkinsons disease (PD) reappears later after a full remission from DIP. However, it is difficult to predict the prognosis in patients with DIP. Herein, we evaluated whether the combined use of (18)F-N-(3-fluoropropyl)-2 beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane (FP-CIT) PET and cardiac MIBG scintigraphy can be used to help distinguish the prognosis in patients with DIP. Among 20 patients enrolled, 16 showed normal DAT uptake and normal myocardial sympathetic innervation. After withdrawal of the suspected drugs, the patients experienced a clinical remission of parkinsonian motor symptoms within 3 months and did not experience any new movement symptoms after at least 2 years of follow-up. Two patients with a moderate decrease in DAT uptake and impaired sympathetic denervation showed worsening of motor manifestations 3 months after discontinuation of the drugs. Another two patients with normal DAT uptake and decreased MIBG uptake, presented full remission of motor symptoms within 2 months after discontinuation of the drugs. However, these two patients eventually developed parkinsonism within 2 years of the follow-up period. The follow-up scans revealed severe decreased DAT uptake in the putamen and similar ranges of cardiac sympathetic denervation. The results suggest that the combined use of these techniques can predict the prognosis of DIP and suggest a proper therapeutic plan for DIP.

Neuropsychiatric symptoms in Parkinson's disease dementia are associated with increased caregiver burden.

Objective Neuropsychiatric symptoms are common in Parkinson’s disease dementia (PDD). Frequent and severe neuropsychiatric symptoms create high levels of distress for patients and caregivers, decreasing their quality of life. The aim of this study was to investigate neuropsychiatric symptoms that may contribute to increased caregiver burden in PDD patients. Methods Forty-eight PDD patients were assessed using the 12-item Neuropsychiatric Inventory (NPI) to determine the frequency and severity of mental and behavioral problems. The Burden Interview and Caregiver Burden Inventory were used to evaluate caregiver burden. Results All but one patient showed one or more neuropsychiatric symptoms. The three most frequent neuropsychiatric symptoms were apathy (70.8%) and anxiety (70.8%), followed by depression (68.7%). More severe neuropsychiatric symptoms were significantly correlated with increased caregiver burden. The domains of delusion, hallucination, agitation and aggression, anxiety, irritability and lability, and aberrant motor behavior were associated with caregiver stress. After controlling for age and other potential confounding variables, total NPI score was significantly associated with caregiver burden. Conclusions The results of this study confirm that neuropsychiatric symptoms are frequent and severe in patients with PDD and are associated with increased caregiver distress. A detailed evaluation and management of neuropsychiatric symptoms in PDD patients appears necessary to improve patient quality of life and reduce caregiver burden.

Association between nocturnal/supine hypertension and restless legs syndrome in patients with Parkinson's disease.

BACKGROUND AND OBJECTIVE Autonomic disturbances and sleep problems are common non-motor symptoms in patients with Parkinsons disease (PD). Orthostatic hypotension, supine hypertension (SH), and nocturnal hypertension (NH) are inter-related in patients with PD. These abnormalities might be associated with restless legs syndrome (RLS), which occurs predominantly at rest or during sleep. Few reports have suggested an association between circadian blood pressure disturbances and RLS in the general population. We evaluated the relationship between neurocardiovascular blood pressure alterations and RLS in patients with early PD. METHODS A total of 225 patients, newly diagnosed with PD, were included in the study. RLS was diagnosed by the International Restless Legs Syndrome Study Groups diagnostic criteria. Orthostatic vital signs and ambulatory 24-h blood pressure were monitored and recorded. RESULTS Thirty-six (16.0%) participating patients had RLS. SH and NH were more frequent in the PD+RLS group than in the group without RLS. Supine blood pressure, orthostatic decline in blood pressure, nighttime blood pressure, and the standard deviation of systolic blood pressure were significantly higher in the PD+RLS group than in the group without RLS. CONCLUSION RLS is related to nocturnal/supine hypertension and blood pressure fluctuations, suggesting a neuropathological association between autonomic and sleep dysfunctions in patients with PD. RLS may be a determinant of neurocirculatory abnormalities. Detecting and effectively treating RLS might slow the rate of pressure-related neurocardiovascular damage in dysautonomic patients with PD.

Subcortical whiter matter hyperintensities within the cholinergic pathways of patients with dementia and parkinsonism.

BACKGROUND AND PURPOSE White matter hyperintensities (WMHs) in the cholinergic pathways are associated with cognitive performance in Alzheimers disease (AD) and Parkinson disease dementia (PDD). This study aimed to evaluate the relationship between loss of white matter cholinergic pathways and cognitive function in patients with AD, diffuse Lewy body disease (DLB), and PDD. METHODS The subjects included 20 patients with AD, 17 with DLB, 21 with PDD, and 20 healthy controls. The extent of WMHs within cholinergic pathways was assessed using the Cholinergic Pathways Hyperintensities Scale (CHIPS) and was compared among the different diseases. RESULTS The mean CHIPS scores were similar among the three dementia groups (AD vs. DLB vs. PDD = 34.6 ± 17.9 vs. 32.4 ± 14.1 vs. 31.8 ± 14.5, p = 0.781 by ANCOVA) and higher than those of controls (11.5 ± 7.6, p = 0.001 by ANCOVA). CONCLUSIONS Losses of cholinergic pathways were similar among AD, DLB, and PDD groups, and more severe cognitive dysfunction was associated with elevated WMHs. These findings suggest that interruption of acetylcholine pathways may be related to cognitive dysfunction in these three diseases, even though they have different pathological mechanisms.

Orthostatic hypotension and cardiac sympathetic denervation in Parkinson disease patients with REM sleep behavioral disorder

BACKGROUND Rapid eye movement (REM) sleep behavioral disorder (RBD), orthostatic hypotension (OH), and cardiac sympathetic denervation were commonly observed in PD and are related in both the premotor and motor periods. This study is intended to evaluate if the OH and cardiac sympathetic denervation found in PD are associated with RBD. METHODS Among 94 non-medicated and mild PD patients, 53 had RBD. Orthostatic vital signs and ambulatory 24-hour blood pressure values were recorded. (123)I-metaiodobenzylguanidine (MIBG) cardiac scintigraphy as obtained in all patients. The association between orthostatic hypotension, supine hypertension, nocturnal hypertension, non-dipping, myocardial MIBG uptake, and RBD was analyzed. RESULTS RBD was associated with orthostatic hypotension. Patients with RBD had higher systolic blood pressure changes during orthostasis and lower myocardial MIBG uptake than patients without RBD and controls. Patients with OH also had lower mean H/M ratios those in the non-OH group. CONCLUSION This study showed that RBD was closely associated with OH and cardiac sympathetic denervation in patients with early and mild PD. The result also suggests that impaired cardiac sympathetic innervation could be the mechanism behind OH in PD. This association may be closely correlated with Braak alpha-synuclein pathogenetic sequences, which would account for the clinical spectrum of PD.

Effect of Rivastigmine on Behavioral and Psychiatric Symptoms of Parkinson's Disease Dementia.

Objective A recent study showed that rivastigmine and memantin improved behavioral and psychiatric symptoms of dementia (BPSD) in Alzheimer’s dementia. Furthermore, according to recent guidelines presented by the Movement Disorder Society, rivastigmine is efficacious for the treatment of dementia in Parkinson’s disease (PD). We investigated the efficacy of rivastigmine for BPSD in patients with Parkinson’s disease dementia (PDD). Methods Twenty-three patients in whom cognitive impairment occurred at least one year after a diagnosis of PD participated in this open-label trial. Cognitive, psychiatric, and motor symptoms were assessed before and after 24 weeks of treatment with rivastigmine using unstructured clinical assessments and rating scales including the Unified Parkinson’s Disease Rating Scale, Mini-Mental State Examination (MMSE), and the Neuropsychiatric Inventory. Results Age (± standard deviation) was 74.7 ± 5.9 years, average duration of PD was 3.5 ± 3.7 years, Hoehn and Yahr scores were 2.2 ± 0.8, and baseline MMSE scores were 19.1 ± 4.2. Improvements in global mental symptoms and neuropsychiatric symptoms were significant; among them, hallucination, depression and appetite changes improved. Caregiver distress significantly decreased, including distress resulting from hallucinations, depression, apathy, and appetite changes. Conclusions Although controlled trials are required, the findings suggest that rivastigmine is useful for control of several neuropsychiatric symptoms and beneficial for caregiver distress in patients with PDD.