Hyung-Eun Park

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.

Normal ‘heart’ in Parkinson's disease: is this a distinct clinical phenotype?

Reduction of metaiodobenzylguanidine (MIBG) uptake has been observed in almost all patients with Parkinsons disease (PD), associated with hyposmia, orthostatic hypotension and rapid eye movement sleep behavioral disorder (RBD). In contrast, a subgroup of patients with PD with normal MIBG uptake have been reported to have milder disease and preserved cognition compared with those with lower MIBG. The aim of this study was to investigate whether non‐motor manifestations of PD differ between patients with normal and abnormal myocardial MIBG uptake.

Autonomic Nervous System Dysfunction in Patients With Parkinson Disease Having Depression

Background and Aim: Both depression and cardiovascular autonomic dysfunctions, such as orthostatic hypotension, supine hypertension, and the absence of normal nocturnal blood pressure (BP) fall (“nondipping”), occur relatively commonly in Parkinson disease (PD); however, the relationship between depression and cardiovascular autonomic abnormalities has not been established. In this study, we sought to determine whether the cardiovascular autonomic abnormalities found in PD are associated with depression. Methods: Among 129 nondemented, levodopa-naive patients with mild PD, 44 had depression. Orthostatic vital signs and ambulatory 24-hour BP monitoring were recorded, and geriatric depressive scales were obtained in all patients. Associations between orthostatic hypotension, supine hypertension, nocturnal hypertension, nondipping, and depression were analyzed. The ratio of the standard deviation of 24-hour heart rate to that of systolic BP (SBP) was utilized as an index of baroreflex–cardiovagal function. Results: Depression was associated with orthostatic hypotension, and patients with depression had higher SBP change during orthostasis and attenuated cardiovagal dysfunction as observed during ambulatory BP monitoring. Across individuals, values for orthostatic changes in BP were correlated with values for geriatric depressive scale. Conclusion: Depression is associated with neurocirculatory abnormalities—especially orthostatic hypotension—in early PD. Although the association does not imply causation, this result suggests that depression in PD might be associated with functional impairment of the autonomic nervous system and its pathologic substrate.

Association between urine protein/creatinine ratio and cognitive dysfunction in Lewy body disorders

BACKGROUND Impaired renal function and proteinuria have been associated with cognitive impairment and dementia. Chronic kidney disease is considered to be an independent risk factor for Lewy body spectrum disorders (LBD). However, few studies have mentioned an association between proteinuria and cognition in LBD. We investigated the relationship between proteinuria and cognitive dysfunction in patients with Parkinsons disease (PD) and dementia with Lewy bodies (DLB). METHODS Among 186 patients with LBD, 53 had PD-normal cognition (PD-NC), 76 had PD-mild cognitive impairment (PD-MCI), 43 had PD-dementia (PDD) and 14 had DLB. The urine protein/creatinine ratio was calculated using the spot urine test and brain magnetic resonance scans was obtained in all patients. RESULTS The urine protein/creatinine ratio was significantly higher in patients with PDD and DLB than in those with PD-MCI, PD-NC patients and healthy controls, and was correlated with white matter hyperintensities on magnetic resonance imaging. All abnormal neuropsychological test results were associated with increased urine protein/creatinine ratio. After controlling for age, education, symptom duration, diabetes mellitus, hypertension, and parkinsonian motor severity, the urine protein/creatinine ratio was significantly associated with decreased cognition. CONCLUSION The urine protein/creatinine ratio was associated with cognitive status in LBD. These finding suggests that increased protein excretion is associated with cognitive dysfunction in patients with LBD.

123I-MIBG myocardial scintigraphy and neurocirculatory abnormalities in patients with dementia with Lewy bodies and Alzheimer's disease

BACKGROUND Although adoption of new clinical criteria for dementia with Lewy bodies (DLB) leads to an increase in the proportion of patients diagnosed with probable DLB, the sensitivity of clinical diagnostic criteria of DLB is low, and there are no generally accepted clinical or imaging biomarkers to distinguish DLB from other types of dementia. In this study, we investigated whether neurocirculatory abnormalities and cardiac sympathetic denervation differed in controls and patients with subjective memory impairment (SMI), mild cognitive impairment (MCI), Alzheimers disease (AD), and DLB. We also assessed whether spontaneous features of Parkinsonism might be related to the neurocirculatory abnormalities and cardiac sympathetic denervation found in DLB. METHODS Twenty-two consecutive patients with probable DLB were enrolled in this study; 25 age-matched controls, 14 SMI, 24 MCI, and 37 AD patients were also evaluated. Metaiodobenzylguanidine (MIBG) uptake was assessed using the ratio of the heart to the upper mediastinum (H/M ratio), and orthostatic vital signs and ambulatory 24-hour blood pressure monitoring values were recorded. RESULTS The mean H/M ratio was significantly lower and the proportion of orthostatic hypotension was higher in patients with DLB than in controls, SMI, MCI and AD patients. In patients with DLB, spontaneous Parkinsonism was not related to the degree of cardiac sympathetic denervation nor did it influence neurocirculatory abnormalities. CONCLUSION Our results suggest that MIBG scintigraphy and autonomic function tests may be useful for distinguishing between DLB and AD in clinical practice. Myocardial postganglionic sympathetic denervation and autonomic dysfunctions are present in patients with DLB regardless of spontaneous Parkinsonism.

Cardiovascular autonomic dysfunctions in elderly patients with essential tremor: comparison with healthy controls

AbstractsQuestionnaire-based analyses show that patients with essential tremor (ET) may have several autonomic dysfunctions, especially in the cardiovascular and genitourinary domains; yet the laboratory correlates of autonomic dysfunction in ET are unknown and have not been studied. Herein, we explored whether sympathetic and parasympathetic functions differed between control subjects and patients with ET. Seventy-five elderly patients with ET were enrolled in this study, along with 25 age-matched controls. Orthostatic vital signs, ambulatory 24-h blood pressure monitoring and 24-h Holter monitoring values were recorded and metaiodobenzylguanidine (MIBG) uptake was assessed using the heart-to-mediastinum ratio (H/M ratio). The frequencies of orthostatic hypotension, supine hypertension, nocturnal hypertension and non-dipping were not different between the ET patients and the controls, although ET patients had more episodes of orthostatic intolerance. The ET group also had similar heart rate variations as the control group for all the time-domains. The mean H/M ratios for the ET group were not statistically different from that of the control group. This result proves that the autonomic control of the cardiovascular system is normal in ET.

Acute Chorea Onset after Hot Food Consumption in a Patient with Moyamoya Disease

Dear Sirs, Moyamoya disease is characterized by a progressive narrowing or occlusion of the terminal portion of the internal carotid arteries and the proximal part of the anterior and middle cerebral arteries, with a concomitant development of abnormal collateral vessels [1]. Common clinical presentations in childhood are ischemic stroke or transient ischemic attack, headache and convulsion [1]. Involuntary movements in patients with moyamoya disease are uncommon, occur in only 3 to 6% of patients [2], and mostly in children. These involuntary movements include chorea, hemidystonia, hemichoreoathetosis, and paroxysmal dyskinesia [2], and are attributed to ischemic changes in the basal ganglia-thalamocortical circuits. Here, we report on a 17-year-old female patient who had an involuntary choreiform movement in her right hand that was associated with moyamoya disease. This symptom, along with hyperventilation, developed immediately after eating hot noodles. The symptom was usually aggravated under stressful conditions such as student assessments and regressed when at rest. The patient had no familial history of chorea or other movement disorders, and she denied the use of any drugs. There was no family history of neurological diseases. On examination, the patient presented with choreic movements involving the right arm. The involuntary movement was a jerky and irregular athetoid movement (Supplementary Video in the online-only Data Supplement). In addition, there was mild slowness with a decremental response observed in the both arms. Neither rigidity nor a rest tremor was observed. The choreoathetoid movement was not present during sleep. The patient’s mental status was normal, and the cranial, motor and sensory nerve examinations showed no other abnormality. The routine laboratory tests, including a complete blood count, fasting glucose and glycosylated hemoglobin A1c, liver enzymes, blood urea nitrogen, creatinine, electrolytes, the erythrocyte sedimentation rate, thyroid functions, serum ceruloplasmin, urine and serum copper, vitamin B1, vitamin B6, and niacin were within the normal limits. The antinuclear antibody and antiphospholipid antibody tests were negative. Genetic tests for Huntington’s disease and spinocerebellar ataxia type 17 were normal. Magnetic resonance imaging (MRI) of the brain showed a low signal intensity on the right parieto-occipital area and multiple flow-voids in both basal ganglia on T2-, T1-, and fluid attenuation inversion recovery-weighted images (Figure 1A, ​,B,B, and ​andC).C). Contrast-enhanced MRI showed diffuse leptomeningeal enhancement along the cortical sulci and a strong enhancement of perforating arteries in the basal ganglia and deep white matter (“ivy sign”) (Figure 1D and ​andE).E). Magnetic resonance cerebral angiography demonstrated severe stenosis of both internal carotid arteries at the supraclinoid portion with numerous collateral vessels (Figure 1F). A 99mTc-hexamethylpropylene amieoxime brain single photon emission computed tomography showed decreased perfusions in the right temporo-occipital cortex, bilateral fronto-temporal areas, and in both basal ganglia (Figure 1G). Digital subtraction cerebral angiography confirmed the moyamoya disease Suzuki grade IV (Figure 1H, ​,I,I, and ​andJJ). Figure 1. A, B, and C: Magnetic resonance imaging (MRI) of the brain showed a low signal intensity on the right parieto-occipital area and multiple flow-voids in both basal ganglia on T2-, T1-, and fluid attenuation inversion recovery-weighted images. D and E: ... The clinical presentations of pediatric moyamoya disease are associated with cerebral ischemia, which causes migraine-like headaches, epileptic seizures, and cerebral infarction [1]. The symptoms are characteristically induced by hyperventilation or breath holding, such as that during crying or playing an instrument [3]. These neurological events appear to have a vasoactive mechanism that is responsive to an acid-base imbalance, but not simply thrombogenic mechanisms [4]. In addition, some patients may experience an ischemic attack after eating hot and spicy noodles. Chorea complicated by moyamoya disease as the first manifestation is extremely rare. In addition, the occurrence of chorea during a specific daily activity such as eating hot noodles is of particular interest. This case suggests that chorea relates directly to hyperventilation and the associated hypocarbia, which could result in profound vasoconstriction and vasospasm [4-6]. In the present patient, an ischemic lesion was found only in the right parieto-occipital area, which was on the ipsilateral side of the hemichorea. The occurrence of a right hemichorea in the present patient is difficult to explain. Some studies have reported ipsilateral ischemic lesions in moyamoya disease and chorea [6]. However, these studies did not provide any association between hemichorea and an ipsilateral ischemic lesion. We also cannot suggest any association between hemichorea and an ipsilateral parenchymal lesion. The patient’s symptom has not disappeared, but has been fluctuating. The chorea is usually aggravated in stressful conditions and is regressed when at rest. We speculate that the hypoperfusion of the left basal ganglia and frontal cortex is associated with a transient aggravation of the right hemichorea. An interruption of the basal ganglia-thalamocortical circuits could have caused the involuntary movements presented in the present patient. Although hyperventilation-related hypoperfusionischemia is the main pathology for chorea in patients with moyamoya disease, to the best of our knowledge, the occurrence of chorea immediately after eating hot foods is rare. This case represents another example of chorea in moyamoya disease that is associated with vasospasm and ischemia.

Hairdresser dystonia: An unusual substantia nigra hyperechogenicity

Task-specific dystonia and occupational cramps present as focal excessive muscle contractions that develop after long-term repetitive practice of highly skilled and overlearned tasks. It commonly affects the upper extremities and includes writers cramp, tailors dystonia, and shoemakers dystonia [1]. Recently, a peculiar form of dystonia was observed in a hairdresser [2,3]. This report describes the case of a 43-year-old right-handed hairdresser who complained of right hand spasms and tremblingwhile cutting hair. He began his career 15 years prior to presentation, and for the first 12 years he did not have any problems. For the last three years, he had difficulty cutting customers hair with scissors, characterized as stiffness and loss of dexterity with his right hand after a few seconds of scissoring. He also experienced trembling in his fingers with this task. At first, the discomfort was restricted to the hand and it only occurred while using scissors. Later, the muscle tightness extended beyond his hand and marched toward his shoulder. He complained of spasmodic twitching of the elbow with flexion and internal rotation during the activity. As his symptoms progressed, he experienced similar difficulty while using a hair straightener. He also experienced subtle clumsiness with his right upper extremity during other tasks, although it did not affect his daily activities. His symptoms did not progress to other body parts. The patient did not have posterior neck discomfort or radiating pain, fluctuating muscle fatigability, or myalgia. The patient denied anymedical problems or traumatic events, andwas not exposed to any neuroleptics. His family members did not have any movement disorders. On examination, no dystonia, rigidity or tremors of the extremities were seen at rest. The posture was upright and the gait was normal. He had mild slowness without fatigability of the right upper extremity during finger tapping and alternating hand movements (Video). When scissoring with his right hand, the patient exhibited spasmodic contraction of the hand muscles and trembling, which eventually slowed. The spasm lasted as long as he continued using the scissors. He also manifested intermittent dystonic posturing of the elbow. While using a hair-straightener similar posturing was also observed in the right upper extremity. There were no overflowmuscle contractions

Rhinitis-induced anosmia leads to the disappearance of olfactory-triggered migraine attacks

Dear Editor, Many conditions have been shown to provoke migraines and most patients have one or more typical precipitating factors. Odours are one of the trigger factors known to provoke migraines with relative ease and frequency (1). Osmophobia is more common in patients with migraine than in other headache disorders, and its presence can help distinguish migraine from other primary headaches (2). Previous studies have suggested that the relationship between odour and migraine involves the peripheral trigemino-nociceptive system or neuronal hyperexcitability of central trigeminal structures (1). However, the exact mechanism through which odour precipitates migraine attacks and the importance of this mechanism are unclear. We report a 52-year-old woman suffering from migraines triggered by noxious odours, who became migraine-free after she lost her olfactory function following an episode of severe rhinitis. The patient has suffered from headaches since her twenties. Her typical headaches were a seven out of 10 in severity, pulsating in nature, involved her right temporal area and were associated with nausea. Most attacks were triggered by chemical odours including car exhaust, perfumes and tobacco smoke, among others. Her migraines typically lasted for 24– 36 hours and occurred two to three times per month. Four months before her visit to our neurology clinic, the patient had an upper respiratory infection (URI) with runny nose and coughing. After recovery from the URI, she reported that she could not smell anything. Three months later, her anosmia had not improved. She underwent rhinoscopic examination that revealed atrophic mucosae in the nasal cavity; the patient scored zero points in smell detection and identification tests. Her neurological examination and the brain magnetic resonance imaging were normal. Surprisingly, after the patient became anosmic, the migraines ceased. Initially, she was treated for anosmia only with a nasal steroid spray. After 2 weeks of nasal spray treatment, the patient reported no improvement. The patient received stellate ganglion blocks 12 times, which are known to be effective in treating anosmia. However, her sense of smell did not recover, the results of follow-up tests did not vary from baseline and she did not experience any migraines for the following 12 months. This case illustrates how odour can be an important migraine trigger factor. The injury of olfactory nerve terminals along with atrophy of the nasal mucosa can reduce or prevent migraine attacks. This case adds to clinical examples explaining the pathophysiology of olfactory-induced migraine attacks via transient receptor potential ankyrin 1 (TRPA1) pathways (1). Irritants into the nasal mucosa can produce meningeal vasodilatation by a TRPA1and Calcitonin generelated peptide (CGRP) -dependent mechanism. It is possible that the disappearance of migraine was unrelated to anosmia; thus, other factors cannot be ruled out as the cause of this condition. In particular, the possibility that anosmia-treatment regimens could influence migraine frequencies should also be considered (3). In summary, we experienced a patient with migraine apparently triggered by odours who became migrainefree after she lost her olfactory function. We hypothesize that sensory factors can be important triggers in migraines, as were proven experimentally.