Higher prevalence of idiopathic normal pressure hydrocephalus-like MRI features in progressive supranuclear palsy: An imaging reminder of atypical parkinsonism.

OBJECTIVES: The classic triad of idiopathic normal pressure hydrocephalus (NPH) encompass gait disturbance, cognitive impairment, and urinary incontinence. These symptoms overlap with parkinsonism but with distinct treatment. Lacking applicable differentiation also hampers the prediction to therapeutic response. Here, we try to clarify this issue among different Parkinsonian syndromes and propose some innovative thinking while approaching a patient with parkinsonism and hydrocephalus concomitantly. METHODS: Twenty-four patients with clinical probable multiple system atrophy (MSA), 34 with probable progressive supranuclear palsy (PSP), and 58 with sex- and age-matched Parkinson's disease (PD) were enrolled. Evans' index (EI), callosal angle (CA), antero-posterior (AP) diameter of the midbrain, length of the midbrain tegmentum diameter (MBTegm ), and disproportionately enlarged subarachnoid space hydrocephalus (DESH) were evaluated using the conventional MRI. Logistic regression was applied to identify the independent variables in hydrocephalus. RESULTS: Patients with PSP had higher mean EI than those with MSA and PD. Around 38.2% of patients with PSP had accompanied hydrocephalus (EI > 0.3). Parkinsonism subtypes (PD, MSA, or PSP), AP diameter of the midbrain, and MBTegm were significantly different among patients with and without hydrocephalus. After regression analysis, parkinsonism subtype stood out to be the most key risk factor of hydrocephalus. The comparison between patients with PSP with and without hydrocephalus did not disclose specific clinical characteristics or risk factors. CONCLUSIONS: This study demonstrates that the presence of NPH-like MRI features is much higher in PSP patients, and this tendency is decided upon the determination of parkinsonism subtype. Sharing pathophysiological characteristics in these two diseases is implied. More diagnostic tools are needed to better differentiate the two diseases and decide the treatment. To closely observe hydrocephalic parkinsonism patients and well inform the possible limited shunting benefits if PSP core features appear, will be more pivotal and practical at present clinical practice.

Autonomic impairment in treatment-naive patients with chronic hepatitis B and C infections.

BACKGROUND: Peripheral neuropathy is not an uncommon manifestation in patients with chronic hepatitis. The role of cryoglobulin (CG) in neuropathy in patients with chronic hepatitis remains controversial. There is limited information about the autonomic neuropathy in chronic hepatitis. This study aimed to evaluate autonomic function in treatment-naive patients with chronic hepatitis B or hepatitis C infection and to elucidate the association between autonomic neuropathy and CG in these patients. METHODS: A total of 29 treatment-naive patients with chronic, yet mild degrees of hepatitis B or C infection were evaluated for autonomic function, including those in the sympathetic sudomotor, cardiovagal, and adrenergic domains, to compare with the control subjects. The autonomic impairment was graded using the Composite Autonomic Scoring Scale. Then, association analyses between autonomic parameters/scores and CG were performed. RESULTS: Patients with chronic hepatitis B or C infection had significantly worse autonomic function than control subjects, especially in the sudomotor and cardiovagal domains. The autonomic manifestations in cases with and without CG were similar. There was no significant difference in autonomic dysfunction between patients with hepatitis B and C infections. CONCLUSION: The study demonstrated that autonomic neuropathy was not uncommon in patients with chronic hepatitis B or C infection. There was no association between autonomic neuropathy and CG.

Recessively-Inherited Adult-Onset Alexander Disease Caused by a Homozygous Mutation in the GFAP Gene.

BACKGROUND: Alexander disease (AxD) is an autosomal-dominant leukodystrophy caused by heterozygous mutations in the glial fibrillary acidic protein (GFAP) gene. OBJECTIVES: The objective of this report is to characterize the clinical phenotype and identify the genetic mutation associated with adult-onset AxD. METHODS: A man presented with progressive unsteadiness since age 16. Magnetic resonance imaging findings revealed characteristic features of AxD. The GFAP gene was screened, and a candidate variant was functionally tested to evaluate causality. RESULTS: A homozygous c.197G > A (p.Arg66Gln) mutation was found in the proband, and his asymptomatic parents were heterozygous for the same mutation. This mutation affected GFAP solubility and promoted filament aggregation. The presence of the wild-type protein rescued mutational effects, consistent with the recessive nature of this mutation. CONCLUSIONS: This study is the first report of AxD caused by a homozygous mutation in GFAP. The clinical implication is while examining patients with characteristic features on suspicion of AxD, GFAP screening is recommended even without a supportive family history. © 2020 International Parkinson and Movement Disorder Society.

Type III Secretion System Translocon Component EseB Forms Filaments on and Mediates Autoaggregation of and Biofilm Formation by Edwardsiella tarda.

The type III secretion system (T3SS) of Edwardsiella tarda plays an important role in infection by translocating effector proteins into host cells. EseB, a component required for effector translocation, is reported to mediate autoaggregation of E. tarda. In this study, we demonstrate that EseB forms filamentous appendages on the surface of E. tarda and is required for biofilm formation by E. tarda in Dulbecco's modified Eagle's medium (DMEM). Biofilm formation by E. tarda in DMEM does not require FlhB, an essential component for assembling flagella. Dynamic analysis of EseB filament formation, autoaggregation, and biofilm formation shows that the formation of EseB filaments occurs prior to autoaggregation and biofilm formation. The addition of an EseB antibody to E. tarda cultures before bacterial autoaggregation prevents autoaggregation and biofilm formation in a dose-dependent manner, whereas the addition of the EseB antibody to E. tarda cultures in which biofilm is already formed does not destroy the biofilm. Therefore, EseB filament-mediated bacterial cell-cell interaction is a prerequisite for autoaggregation and biofilm formation.

The relationship of leukoaraiosis and the clinical severity of vascular Parkinsonism.

Vascular Parkinsonism (VP) is referred to as secondary Parkinsonian syndrome. It occurs with lacunar state or sub-cortical white matter micro-angiopathy and is highly associated with vascular risk factors and leukoaraiosis, also known as cerebral white matter lesions (WML). This study aimed to assess the prevalence of different vascular risk factors and WML in patients with VP, and their impact on clinical features. Sixty-two consecutive VP patients (70.2 ± 9.2 years) were evaluated for clinical severity using the Unified Parkinson's Disease Rating Scale (UPDRS). WML was assessed and scored on fluid-attenuated inversion recovery T2-weighted (FLAIR) magnetic resonance imaging (MRI). Cerebro-vascular risk factors, WML severity, and the UPDRS for clinical disability were analyzed statistically. There were no associations between WML score and age, sex, hypertension, diabetes, previous stroke, cardiac disease, cigarette smoking, or serum levels of cholesterol and triglyceride. The WML score positively correlated with UPDRS part I (p = 0.035) and part III (p = 0.041) scores. After adjustments for age, gender, stroke history, and use of levodopa, the WML score was associated with the UPDRS total (p = 0.020), part I (p = 0.012), part II (p = 0.039), and part III (p = 0.019) scores. The severity of WML is not associated with conventional vascular risk factors in VP patients but is significantly correlated with the UPDRS total and all sub-scores, which suggests that disruption of the cortico-sub-cortical circuits may lead to impaired mentation, behavior and mood, activities of daily living, and motor performance in these patients.

A novel APP mutation (D678H) in a Taiwanese patient exhibiting dementia and cerebral microvasculopathy.

We report a novel missense mutation, D678H, in the APP gene in a Taiwanese patient who had progressive cognitive decline beginning in middle age. Brain MRI showed leukoencephalopathy, cortical microhemorrhages and focal superficial cortical hemosiderosis, which are consistent with cerebral amyloid angiopathy. A phenotype of combined dementia and cerebral microvasculopathy suggested concurrent increases in brain parenchymal and cerebrovascular beta-amyloid peptide (Aß) deposition in this patient. The promotion of Aß aggregation has been postulated to underlie the pathogenic mechanism of the mutation.

Association between MIF gene polymorphisms and carotid artery atherosclerosis.

Atherosclerosis is a chronic inflammatory disorder. Macrophage migration inhibitory factor (MIF) is a potent cytokine that plays an important role in the regulation of immune responses. Polymorphisms including five- to eight-repeat CATT variants ((CATT)(5-8)) and G-173C in the promoter region of the MIF gene are associated with altered levels of MIF gene transcription. The purpose of the study is to investigate the relationship between promoter polymorphisms of the MIF gene and the severity of carotid artery atherosclerosis (CAA). The severity of CAA was assessed in 593 individuals with a history of ischemic stroke by using sonographic examination, and the MIF promoter polymorphisms of these individuals were genotyped. The carriage of (CATT)7 (compared to genotypes composed of (CATT)5, (CATT)6, or both), carriage of C allele (compared to GG), and carriage of the haplotype (CATT)7-C (compared to genotypes composed of (CATT)5-G, (CATT)6-G, or both) were significantly associated with an increase in the severity of CAA. We conclude that polymorphisms in the MIF gene promoter are associated with CAA severity in ischemic stroke patients. These genetic variants may serve as markers for individual susceptibility to CAA.

[Relationships between spatial distribution of two dominant small-sized fishes and submerged macrophyte cover in Niushan Lake of China].

By using a set of pelagic gillnets with eight mesh sizes, an investigation was made on the spatial distribution of small fishes in submerged macrophyte habitats in a shallow macrophytic lake (Niushan Lake) in the middle reach of Yangtze River in summer, 2005. The fish composition, abundance, and size structure were examined along a biomass gradient of the most dominant submerged macrophyte Potamogeton maackianus. A total of 1124 individuals from 13 fish species were caught during the study period. According to the abundance and occurrence, sharpbelly Hemiculter leucisculus and redfin culter Cultrichthys erythropterus were identified as the two dominant small pelagic fishes in the lake. There existed dome-like relationships between the fish species richness and Shannon diversity index and the submerged macrophyte biomass within its observed range. For the two dominant small fishes, their abundance was significantly positively correlated with macrophyte biomass, and the average sizes of the individuals of H. leucisculus and C. erythropterus were larger in un-vegetated habitat but smaller in heavily vegetated habitats, indicating that the young individuals tended to live in dense submerged macrophyte covers. Other two habitat factors, i. e., water depth and distance to shore, had little effects on the spatial distribution of the two fish species. It was inferred that P. maackianus cover should be the important refuge habitat for the two dominant small-sized fishes in Niushan Lake, and it would be necessary to protect or restore the submerged macrophyte covers including P. maackianus.

An unusual presentation of hypokalemic paralysis with evolving pure motor hemiparesis.

Pure motor hemiparesis is a vascular syndrome that is occasionally mimicked by central or spinal pathologies. However, metabolic neuromuscular disorders have not been reported to mimic this condition. We present a 52-year-old male patient with hypokalemic paralysis who presented with the early symptoms of acute-onset pure motor hemiparesis. Neurological examinations revealed right-sided weakness without bulbar, extraocular, or respiratory involvement. Ischemic stroke was initially diagnosed on the basis of the acute-onset unilateral motor deficit and the patient's history of hypertension, stroke, and previous cerebral infarctions. The right hemiparesis and weakness of the left limbs worsened on the day after admission. The patient's weakness rapidly reversed after correction of hypokalemia, and a diagnosis of hypokalemic paralysis was finally established. This unusual hemineurological presentation should alert medical personnel to the possibility of reversible metabolic neuromuscular disorders, thereby avoiding delayed diagnosis.

Cavernous malformations of the central nervous system combined with cutaneous vascular lesions due to KRIT1 mutation: a case report.

Cavernous malformations (CMs) of the central nervous system can occur in a sporadic condition or as a familial form with an autosomal-dominant inherited pattern. Apart from a family history, some clinical features may help to identify familial CMs. We demonstrate clinical, neuroradiological, pathological, and genetic data of a patient with cerebral and spinal CMs. The presence of multiple cerebral CMs and distinct cutaneous vascular lesions, including hyperkeratotic cutaneous capillary-venous malformations, in this patient suggested familial CMs. A genetic study confirmed a nonsense mutation (c.1708A>T) in the KRIT1 gene.

Association of plasma homocysteine concentration with cerebral white matter hyperintensity on magnetic resonance images in stroke patients.

BACKGROUND: Homocysteine (Hcy) has been recognized as a risk factor for atherosclerosis. White matter hyperintensity (WMH) on MRI has been regarded as a hallmark for cerebral small vascular disease. The study is to investigate the relationship between plasma Hcy level and WMH on a hospital-based cohort of Taiwanese stroke patients. METHODS AND RESULTS: A total of 352 consecutive stroke patients (64.7+/-11.2 years) were included. Severity of WMH was semi-quantitatively evaluated with a scoring system. The top WMH score tertile was defined as severe white matter change (sv-WMH). Associations between Hcy tertile levels and sv-WMH were examined, adjusting for demographics and atherosclerosis risk factors. Subjects in the top Hcy tertile (>10.25 micromol/L) had higher WMH scores and prevalence of sv-WMH than those in the middle and in the bottom tertile. The adjusted odds ratio of having sv-WMH was 2.04 (95% confidence interval 1.20-3.47, p=0.008) for the top Hcy level tertile than for the lower two tertiles combined. CONCLUSION: Hcy is a risk factor for cerebral white matter lesion in stroke patients. Even mild hyperhomocysteinemia can significantly increase severity of cerebral microangiopathy.

Crossed cheiro-oral syndrome.

OBJECTIVES: Cheiro-oral syndrome is characterized by sensory impairment confined to perioral area and ipsilateral fingers/hand. It results from an involvement of the ascending sensory tracts above the pons. However, a crossed pattern of perioral and acral paresthesia was rarely reported before. PATIENTS AND METHODS: This study reports the neuroanatomic relationship, course and clinical significance of perioral and contralateral acral paresthesia in four patients. We term it the crossed cheiro-oral syndrome. RESULTS: All patients had lateral or dorsolateral medullary infarctions that were ipsilateral to their perioral paresthesia. The contributory origin is considered a diagonal lesion involving the par oralis fibers within the descending trigeminal sensory tract and acral portion of the lateral spinothalamic tract at the lateral portion of medulla oblongata. Despite of a restricted sensory disturbance at initial, progressive neurological disability terminated to Wallenberg's syndrome ensued in three patients and disabling deficits persisted in two of them. CONCLUSION: The crossed cheiro-oral syndrome seems a mild form of Wallenberg's syndrome. Therefore, it predicts medullary involvement and is also a warning sign for progression.

Kennedy disease mimics amyotrophic lateral sclerosis: a case report.

Kennedy disease (KD) is an X-linked inherited motor neuron disease that is often accompanied by androgen insensitivity. Its estimated incidence in the US is approximately 1 case in 40,000 men. KD has also been reported in individuals of different racial backgrounds, especially in Japanese but the prevalence rate in Taiwan has not been fully investigated. Here we report a case of KD definitely diagnosed by abnormal expansion of a polymorphic tandem cytosine-adenine-guanine (CAG) triplet repeat in the first exon of the androgen receptor gene. The direct genotyping from polymerase chain reaction product is subsequently performed utilizing capillary electrophoresis. The patient's neurological conditions mimic amyotrophic lateral sclerosis (ALS). Since these two diseases have different etiologies and prognosis, it reminds us the necessity to rule out KD in face with a suspected male case of ALS.

Association between cerebral microbleeds and prior primary intracerebral hemorrhage in ischemic stroke patients.

OBJECTIVE: To investigate association between cerebral microbleeds (CMB) and prior intracerebral hemorrhage (ICH) on MRI and topographic correlation of the two types of lesions. PATIENTS AND METHODS: Two hundred and sixty consecutive patients (67.0+/-11.1 years) with ischemic stroke were included. CMB and prior ICH were assessed on T2-gradient-echo MRI. The presence and number of CMB as predictors for prior ICH were examined. Topographic correlations between CMB and ICH lesions in patients with prior ICH in the infratentorial, basal ganglionic/thalamic and cortico-subcortical regions were tested. RESULTS: CMB were observed in 113 (43.5%) patients and a total of 50 prior primary ICH lesions were observed in 39 (15.0%) patients. Among the ICH lesions, 39 (78%) were asymptomatic. Presence of CMB (odds ratio 2.53, p=0.015) and number of CMB (odds ratio 1.11, p<0.001) were independent determinants for prior ICH. Topographic correlation between CMB and ICH was significant in the basal ganglionic/thalamic region (p=0.017), but not in the infratentorial (p=0.548) or cortico-subcortical regions (p=0.389). CONCLUSION: CMB were associated with prior ICH on MRI of patients with ischemic stroke. CMB in the basal ganglion or thalamus was associated with prior ICH in the same region.

Cheirobuccal sensory syndrome.

Two patients presented with sensory impairments confined to their right intraoral cheek and right first three fingers. An objective decrease of pinprick pain was detected at these sites. Neuroimaging illustrated recent infarcts in the contralateral ventral thalamus of both patients. The intraoral and cheiral sensory impairments resolved within two months after onset. We coined the term "cheirobuccal sensory syndrome" to describe these cases. The clinical significance and pathogenesis of this peculiar syndrome are discussed.

Decreased muscular radionuclide uptake in Tc-99m MIBI scintigraphy during paralytic phase of thyrotoxic periodic paralysis.

The underlying pathophysiology of thyrotoxic periodic paralysis (TPP) is still obscure. From histologic surveys, vacuole formation and abundant mitochondrial abnormalities ranged from swelling, matrical pallor, pleomorphism, and reduced cristae were often disclosed in the muscle fibers during paralytic periods. In a 47-year-old man experiencing 2 episodes of transient paralysis, hyperthyroidism with TPP was diagnosed. During the acute paralytic phase, a significant reduction of radionucleotide uptake in the quadriceps on Tc-99m sestamibi scintigraphy was found, aside from the previous morphologic findings, that it further suggests impaired mitochondrial integrity and cellular viability in TPP.

Cerebellar hemorrhage provoked by combined use of nattokinase and aspirin in a patient with cerebral microbleeds.

Nattokinase is used as a health-promoting medicine for preventing thrombosis due to its fibrinolytic activity. Cerebral microbleed is remnant of blood extravasations from the damaged vessels related to cerebral microangiopathies. We report a patient, having used aspirin for secondary stroke prevention, who had an acute cerebellar hemorrhage after taking nattokinase 400 mg daily for 7 consecutive days. In addition to the hemorrhagic lesion, multiple microbleeds were demonstrated on brain MR images. We suggest that nattokinase may increase risk of intracerebral hemorrhage in patients who have bleeding-prone cerebral microangiopathy and are receiving other antithrombotic agent at the same time.

Uncoupling of protein C and antithrombin III activity in cerebral ischemia patients associated with cutis marmorata.

PURPOSE: Cutis marmorata is a cutaneous livedoid disorder which can be differentiated from livedo reticularis in both clinical and pathological presentations. Unlike Sneddon syndrome, a detailed immunocoagulation profile has not yet been delineated for cutis marmorata in patients with cerebral ischemia. METHODS: To analyze the immunocoagulation profile in cutis marmorata patients associated with cerebral ischemia (CMCI) in a series of 135 cerebral ischemia patients. RESULTS: A total of 32 patients were found to have cutis marmorata. The blood protein C activity, protein S activity, antithrombin III activity, platelet count, fibrinogen and frequency of abnormal antiphospholipid antibody level were similar among 32 CMCI patients, 103 cerebral ischemia patients without cutis marmorata, and 35 healthy subjects. However, uncoupling of protein C and anti-thrombin III was observed in CMCI patients. Serum antinuclear antibody and Venereal Disease Research Laboratory were not detected in these patients. CONCLUSION: Cutis marmorata is not uncommon in our ischemic stroke patient population, and is characterized by uncoupling of protein C and antithrombin III with altered thrombin hemostasis. Our findings raise the need for a careful cutaneous examination in patients with ischemic stroke. Abnormal immunocoagulating profile should alert physicians to the risk for cerebral ischemia even in the absence of other cardiovascular risk factors.