Morphological study of the phrenic nerve to determine a reference value for the myelinated fiber density in elderly individuals.

Phrenic nerves (PNs) play an important role in respiration; however, very few morphological studies have assessed them. This study aimed to provide control reference values, including the density of large and small myelinated PN fibers, for future pathological studies. We assessed a total of nine nerves from eight cases among consecutive autopsy cases registered to the Brain Bank for Aging Research between 2018 and 2019 (five men and three women, mean age 77.0 ± 7.0 years). The nerves were sampled distally, and their structures were analyzed using semi-thin sections stained with toluidine blue. The mean and standard deviation of the density of each myelinated fiber of the PN was 6908 ± 1132 fibers/mm2 (total myelinated fiber), 4095 ± 586 fibers/mm2 (large diameter myelinated fiber; diameter ≥7 µm), and 2813 ± 629 fibers/mm2 (small diameter myelinated fiber; diameter <7 µm). There was no correlation between myelinated fiber density and age. This study provides the density measurement of the human PN myelinated fiber, and these findings can be used as reference values for the PN in elderly individuals.

Rasagiline does not exacerbate autonomic blood pressure dysregulation in early or mild Parkinson's disease.

INTRODUCTION: Orthostatic hypotension (OH) and abnormal blood pressure (BP) fluctuations occur mainly due to noradrenergic dysfunction and are clinically important in patients with Parkinson's disease (PD). They lead to impairments of cognition function, daily activities, and quality of life. Some monoamine oxidase (MAO)-B inhibitors have a sympathomimetic amine, which can be attributed to OH. Therefore, we determined whether rasagiline, a common MAO-B inhibitor used in PD treatment, can contribute to cardiovascular autonomic BP dysregulation in patients with early or mild PD. METHODS: Nineteen patients with early or mild PD were recruited, and tilt test and 24-h ambulatory BP monitoring (ABPM) were performed before and after rasagiline administration. Early or mild PD was defined as patients with de novo (n = 4), levodopa (n = 10), dopamine agonist (n = 1), levodopa and one dopamine agonist (n = 2), levodopa and droxidopa (n = 1), and levodopa and istradefylline (n = 1). Furthermore, patients with motor fluctuation and multiple dopamine agonists were excluded from our study. RESULTS: OH and BP frequency were not significantly exacerbated before or after rasagiline administration. No significant differences of type in BP fluctuation on ABPM and the degree of nocturnal BP falls were found before and after rasagiline administration. The Unified Parkinson's Disease Rating Scale motor score in patients (post-rasagiline administration) was significantly improved compared with before. CONCLUSION: Rasagiline seems to be a suitable medication for Parkinsonian symptoms in patients with early and mild PD. It does not exacerbate cardiovascular autonomic responses, circadian rhythm of BP, or both.

Lewy pathology of the submandibular gland in Lewy body disease: A report of autopsy cases.

Accumulation of phosphorylated α-synuclein in the central and peripheral nervous systems is a histological hallmark of Lewy body disease (LBD), including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and LB-related pure autonomic failure. The submandibular gland is employed as a biopsy site for detecting Lewy pathology; however, the incidence of Lewy pathology in this region in autopsy-proven LBD cases at all stages from an aged Japanese cohort remains unclear. To validate the utility of Lewy pathology of the submandibular gland as a diagnostic biomarker for LBD, we investigated the submandibular gland Lewy pathology in autopsied patients. To determine the specificity, we prospectively evaluated the submandibular gland in 64 consecutive autopsied patients. To determine the sensitivity, we retrospectively assessed the submandibular gland in 168 consecutive autopsied patients who had prodromal or clinical LBD. In the prospective study, Lewy pathology was found in 21 of 64 patients, and nine of those 21 patients had the submandibular gland Lewy pathology. No Lewy pathology was found in 43 patients without CNS Lewy pathology, giving a specificity of 100%. In the retrospective study, Lewy pathology of the submandibular gland was detected in 126 of 168 patients. The sensitivity was 89.1% in PD and 75.4% in DLB. The sensitivity increased with disease progression. These findings support the utility of the submandibular gland biopsy for the pathological diagnosis of LBD.

Frontal lobe dysfunction is associated with reduced DAT-SPECT accumulation in Lewy body disease.

INTRODUCTION: Lewy body disease (LBD) causes olfactory or cognitive dysfunction even before motor symptoms emerge. Recent reports indicate that the dopamine transporter (DAT), which can be imaged using single-photon emission computed tomography (123I-ioflupane SPECT), is related to olfactory and cognitive dysfunction in LBD patients. We suspected that decreased cerebral blood flow (CBF) in the frontal lobe might be involved in these relationships. If so, then the results of these examinations may be useful in assessing the pathological progression of Lewy bodies. METHODS: We retrospectively analyzed the data of 139 de novo consecutive patients with LBD. We used the Odor Stick Identification Test for Japanese (OSIT-J) and the Frontal Assessment Battery (FAB) to evaluate olfactory and frontal lobe dysfunction, respectively. Among the 139 patients, ultimately 84 patients were analyzed and underwent 123I-ioflupane SPECT within 3 months (before or after) of the OSIT-J and FAB. We categorized patients on the basis of whether frontal lobe CBF was reduced (n = 28) or normal (n = 56). RESULTS: The average OSIT-J and FAB scores were 4.0 and 14.1, respectively, and the scores on the two tests were significantly correlated. Furthermore, OSIT-J scores were significantly correlated with the specific binding ratio (SBR) in both groups. The SBR was correlated with FAB scores in patients with reduced CBF in the frontal lobe, but not in those with normal CBF. CONCLUSION: Frontal lobe dysfunction and striatum dysfunction are correlated in LBD patients only after CBF has declined. Also, there is a time lag in the appearance of olfactory dysfunction and frontal lobe dysfunction in LBD patients. As with pathological development, olfaction is impaired earliest, followed by striatal, and then frontal lobe dysfunction.

Neuromyelitis optica spectrum disorder with deafness and an extensive brainstem lesion.

A 49-year-old woman developed vomiting, hiccups, double vision, and bilateral ptosis, after which tinnitus and deafness appeared. Head magnetic resonance imaging (MRI) showed a brainstem lesion focused on the midbrain and pons. Anti-aquaporin 4 (AQP4) antibody was positive, and there was no evidence of optic neuritis or myelitis, leading to the diagnosis of neuromyelitis optica spectrum disorder (NMOSD). The auditory brainstem response (ABR) showed no derivation of wave V on left stimulation and extended latency between waves III and V on right stimulation, so impairment between the midbrain and pons was suspected. It was useful to evaluate head MRI and the ABR for identification of the location of auditory pathway dysfunction.

Lewy pathology of the esophagus correlates with the progression of Lewy body disease: a Japanese cohort study of autopsy cases.

Lewy body disease (LBD) is a spectrum of progressive neurodegenerative disorders characterized by the wide distribution of Lewy bodies and neurites in the central and peripheral nervous system (CNS, PNS). Clinical diagnoses include Parkinson's disease (PD), dementia with Lewy bodies, or pure autonomic failure. All types of LBD are accompanied by non-motor symptoms (NMSs) including gastrointestinal dysfunctions such as constipation. Its relationship to Lewy body-related α-synucleinopathy (Lewy pathology) of the enteric nervous system (ENS) is attracting attention because it can precede the motor symptoms. To clarify the role of ENS Lewy pathology in disease progression, we performed a clinicopathological study using the Brain Bank for Aging Research in Japan. Five-hundred and eighteen cases were enrolled in the study. Lewy pathology of the CNS and PNS, including the lower esophagus as a representative of the ENS, was examined via autopsy findings. Results showed that one-third of older people (178 cases, 34%) exhibited Lewy pathology, of which 78 cases (43.8%) exhibited the pathology in the esophagus. In the esophageal wall, Auerbach's plexus (41.6%) was most susceptible to the pathology, followed by the adventitia (33.1%) and Meissner's plexus (14.6%). Lewy pathology of the esophagus was significantly associated with autonomic failures such as constipation (p < 0.0001) and among PNS regions, correlated the most with LBD progression (r = 0.95, p < 0.05). These findings suggest that the propagation of esophageal Lewy pathology is a predictive factor of LBD.

Olfactory function combined with morphology distinguishes Parkinson's disease.

OBJECTIVE: This study aimed to examine whether the volume of the olfactory bulbs and tracts (OB & T) on magnetic resonance imaging (MRI) is useful for differentiating Parkinson's disease (PD) from PD-related disorders. METHODS: The study group comprised 13 patients with PD, 11 with multiple system atrophy (MSA), five with progressive supranuclear palsy, and five with corticobasal degeneration (PSP/CBD). All patients were evaluated using the odor stick identification test for Japanese (OSIT-J), (123)I-meta-iodobenzylguanidine (MIBG) scintigraphy, and brain MRI. OB & T areas on 1-mm-thick coronal images were measured and summed for volumes. We examined relationships between olfactory function and volume, and cardiovascular dysautonomia. We defined the cut-off values for OSIT-J score or MIBG uptake and OB & T volume to discriminate PD from PD-related disorders and calculated the proportional rate of PD in four categorized groups. RESULTS: OB & T volume was smaller in PD than in MSA or PSP/CBD (p < 0.05 each). The cut-off for detecting PD patients was OSIT-J score <8, heart/mediastinum ratio <1.6, and OB & T volume <270 mm(3). In the group with OSIT-J score <8 and OB & T volume <270 mm(3), the proportion of PD patients among all patients with PD-related disorders was 91%. The rate of probable PD gradually increased as OSIT-J score and OB & T volume decreased (p < 0.001). CONCLUSIONS: Although preliminary, these data obtained from a combined morphological and functional evaluation of OB or cardiovascular dysautonomia could be useful for further differential of PD and other PD-related disorders.

Stiffness parameter ß of cardioembolism measured by carotid ultrasound was lower than other stroke subtypes.

BACKGROUND: We estimated the stiffness parameter ß (ß value), which is useful in the assessment of premature atherosclerosis, among patients with different subtypes of cerebral infarction (CI; eg, small-vessel occlusion, large-artery atherosclerosis, cardioembolism, and other determined and undetermined etiologies) to determine the clinical utility of the ß value in classification of stroke patients into CI subtypes. METHODS: Carotid ultrasonography (ALOKA ProSound SSD-alpha10) was performed in 31 CI patients and 38 control subjects, and the ß value of the bilateral common carotid artery at 2.0 cm proximal to the bifurcation was measured using the echo-tracking method. The relationship between ß value and age was examined, and the ß value was compared among the different CI subtypes. RESULTS: Positive ß value correlated with age in control subjects (R=.69, P<.001) but not in CI patients (R=-.01, P=.996). There was no significant difference in the ß value when comparing control patients and patients with cardioembolic stroke (P=.106), but the ß value were lower in patients with cardioembolic stroke than in patients with noncardioembolic stroke (eg, small-vessel occlusion, large-artery atherosclerosis, and others, P=.009). CONCLUSIONS: The ß value was lower in patients with cardioembolic stroke than in patients with noncardioembolic stroke. The ß value may be useful for estimating the risk of different stroke subtypes.

Abnormal nerve conduction study findings indicating the existence of peripheral neuropathy in multiple sclerosis and neuromyelitis optica.

OBJECTIVE: Chronic inflammatory demyelinating polyneuropathy (CIDP) has been reported in patients with multiple sclerosis (MS). However, there have been limited reports of peripheral neuropathy as a complication of neuromyelitis optica (NMO). In this paper, we showed the characteristics and differences between peripheral neuropathy as a complication of MS and NMO. METHOD: We analyzed a series of 58 MS and 28 NMO patients and evaluated nerve conduction studies (NCS) in 21 MS and 5 NMO patients. RESULTS: Six of the 58 MS and 3 of the 28 NMO patients revealed abnormal NCS findings. Three (5.2%) of the 58 MS patients fulfilled the criteria for CIDP. One (3.6%) of the 28 NMO patients showed peripheral neuropathy at the same time of NMO relapse, although CIDP was not seen in NMO. The other 5 (3 MS and 2 NMO) patients were complicated with neuropathy caused by concomitant diabetes mellitus and Sjögren's syndrome. CONCLUSION: Frequency of abnormal NCS findings might exhibit no significant difference between MS and NMO, although the cause and pathophysiology of peripheral neuropathy were different in MS and in NMO. There might be a group of NMO who were affected simultaneously in the central and peripheral nervous tissues.