Screening for Fabry Disease in Japanese Patients with Young-Onset Stroke by Measuring α-Galactosidase A and Globotriaosylsphingosine.

BACKGROUND: Fabry disease is an X-linked lysosomal storage disorder caused by mutations in GLA, which encodes the enzyme α-galactosidase A (α-Gal A). Although the prevalence of Fabry disease in patients with stroke has been reported to range from 0% to 4%, few cohort studies have examined Japanese stroke patients. We aimed to clarify the prevalence of Fabry disease and the frequency of GLA mutations among patients with young-onset stroke in Japan. METHODS: From April 2015 to December 2016, we enrolled patients with young-onset (≤60 years old) ischemic stroke or intracerebral hemorrhage. We measured α-Gal A activity and the concentration of globotriaosylsphingosine in plasma. Genetic evaluations were performed in patients with low α-Gal A activity or high concentrations of globotriaosylsphingosine. RESULTS: Overall, 516 patients (median age of onset, 52 years old; 120 women) were consecutively enrolled in this study. Five patients (4 men and 1 woman) had low α-Gal A activity, and no patients were detected with the screen for plasma globotriaosylsphingosine levels. The genetic analysis did not identify a causative mutation responsible for classic Fabry disease in any of the patients, but 2 patients (.4%) carried the p.E66Q in GLA. CONCLUSIONS: No patient with Fabry disease was detected in our young-onset stroke cohort.

Carotid Artery Dissection and Ischemic Stroke Originating from Localized Aortic Arch Dissection.

Aortic dissection is an infrequent but important cause of acute ischemic stroke (AIS), and must not be overlooked because of a possible worse outcome, especially with the use of an intravenous recombinant tissue plasminogen activator. We report a case of left carotid artery dissection and AIS originating from localized aortic arch dissection, pathologically caused by cystic medial necrosis in the tunica media.

Localization of CHMP2B-immunoreactivity in the brainstem of Lewy body disease.

Alpha-synuclein (αS) is one of the major constituents of Lewy bodies (LBs). Several lines of evidence suggest that the autophagy-lysosome pathway (ALP) is involved in the removal of αS. We have previously reported that granulovacuolar degeneration (GVD) in neurons involved a subunit of the endosomal sorting complexes required for transport (ESCRT). In this study, we examined the association between alpha-synucleinopathy and autophagy through immunohistochemical analysis of charged multivesicular body protein 2B (CHMP2B), a component of the ESCRT-pathway. We examined the brainstems of 17 patients with Parkinson's disease (PD), incidental Lewy body disease (ILBD), multiple system atrophy (MSA), and Alzheimer's disease (AD) immunohistochemically using antibodies against phosphorylated αS (pαS), phosphorylated tau and CHMP2B. LBs and a proportion of glial cytoplasmic inclusions (GCIs) were immunopositive for pαS and CHMP2B. Neurons containing CHMP2B-immunoreactive granules were detected in PD and ILBD, but not in MSA and AD brains. CHMP2B immunoreactivity was increased in the dorsal motor nucleus of the vagus nerve (DMNX) in PD and ILBD brains, relative to that in MSA and AD. These findings indicate that the ESCRT-pathway is implicated in the formation of αS inclusions, especially in PD and ILBD.

Lumbar puncture-related cerebrospinal fluid leakage on magnetic resonance myelography: is it a clinically significant finding?

BACKGROUND: Post-dural puncture headache (PDPH) due to excessive cerebrospinal fluid (CSF) leakage is a well-known complication of lumbar puncture. Although various factors, especially the type of spinal needle, have been demonstrated to be associated with PDPH, the clinical implications of CSF leakage detected on magnetic resonance myelography (MRM) images remain unclear. The objective of this case-control study was to evaluate the association between radiologically visualized CSF leakage and PDPH. METHODS: Clinical data including patients' age and gender, types of spinal needle, duration of bed rest, interval between lumbar puncture procedures and MRM studies, and incidence of PDPH were compared between patients who were radiologically-positive and -negative for CSF leakage. RESULTS: Of the 22 patients with definite CSF leakage on MRM images, most were asymptomatic (86%, 19/22). The remaining three patients, who were suffering from PDPH, only complained of headaches and were treated conservatively. In a review of patients' clinical data, there were no significant differences in any parameter including the incidence of PDPH between the 22 patients who were radiologically-positive for CSF leakage and the 31 radiologically-negative patients. CONCLUSION: The significance of radiologically visualized CSF leakage should not be overestimated, as most such incidents are not associated with PDPH and do not require any treatment.

Evaluation of luminal and vessel wall abnormalities in subacute and other stages of intracranial vertebrobasilar artery dissections using the volume isotropic turbo-spin-echo acquisition (VISTA) sequence: a preliminary study.

OBJECTIVE: To evaluate the utility of 3D variable refocusing flip-angle volume isotropic turbo-spin-echo acquisition (VISTA) imaging, using a 1.5-T MRI unit, which can minimize flow artifacts, due to its sequence-endogenous flow-void capability, in the diagnosis of intracranial vertebrobasilar artery dissection (VAD). MATERIAL AND METHODS: The presence of intimal flaps, intramural hematomas, vessel dilatations and abnormal vessel enhancements were evaluated on T1-weighted VISTA images from 18 VAD patients with 20 dissected arteries (15 subacute and five at other stages). Additional gadolinium-enhanced T1VISTA images were available for 13 patients. The frequency of flow artifacts on T1VISTA imaging in 70 non-dissected arteries in VAD patients and 12 control subjects was also evaluated. Furthermore, in 13 and eight patients, contrast-enhanced three-dimensional (CE3D) imaging with spoiled gradient-recalled (SPGR) acquisition in steady state and electrocardiographically gated black-blood (BB) T1-weighted imaging (T1WI) were evaluated to compare visualization of false lumens. RESULTS: Intimal flaps, intramural hematomas and dilatations were identified on T1VISTA images in 65% (13/20), 55% (11/20) and 90% (18/20) of VADs, respectively. Abnormal vessel enhancement was recognized in 100% (15/15) of VADs on contrast-enhanced T1VISTA images. Only four normal arteries showed small, thin, linear artifacts. Compared with CE3D-SPGR imaging, T1VISTA imaging depicted false lumens more conspicuously in seven VADs (P=0.02). T1VISTA also revealed intimal flaps and hematomas as did BB T1WI. CONCLUSION: T1VISTA imaging may be useful for diagnosing VAD at subacute stages, as it can reveal vessel wall and lumen abnormalities with a minimum of flow artifacts.

[Nicotine, pesticides, and tobacco, in Three Act Tragedy].

Since one of the main characters in Three Act Tragedy was an actor, the three murders described in the book have been likened to a curtain. The three seemingly unrelated murders were connected at the end of the story, a thrill unique to the author, Agatha Christie. Nicotine was used in all three murders in this book. Nicotine is highly toxic and was one of the main pesticides used until the mid-20th century. Although its use is currently prohibited, neonicotinoid pesticides, which have reduced toxicity, are still being used. Problems with nicotine intoxication include accidental ingestion by young children, green tobacco sickness, and suicide attempts. When nicotine enters the body, it binds to acetylcholine receptors and causes various symptoms.

[Clinical Features of Common Types of Dystonia and Practical Approach for Occupational Dystonia].

Dystonia is a movement disorder characterized by sustained muscle contractions that result in abnormal "patterned" movements and/or postural abnormalities. Based on the accompanying symptoms, dystonia can be classified as isolated (i.e., with dystonia only), combined (i.e., with other movement disorders such as myoclonus), or complex (i.e., with symptoms other than movement disorders such as mental retardation). Moreover, dystonia may affect single or multiple parts of the body and accordingly be classified as focal, segmental, multifocal, hemi, or generalized. The most common type of dystonia is isolated focal dystonia, often accompanied with a specific action (task-specific action). The "task-specificity" uniquely illustrates the nature of dystonia, and this phenomenon is most clearly observed in occupation-related dystonias that include musician's and athlete's dystonia. In this article, we first elucidate the general issues of common focal dystonia (cervical dystonia, blepharospasm, and focal hand dystonia) and then present several educational cases of occupational (task-specific) dystonia with some clinical pearls for practical management.

Comparison of the radioisotope cisternography findings of spontaneous intracranial hypotension and iatrogenic cerebrospinal fluid leakage focusing on chronological changes.

BACKGROUND: Radioisotope cisternography (RICG) is useful for detecting cerebrospinal fluid (CSF) leakage in spontaneous intracranial hypotension (SIH) patients. However, RICG can cause iatrogenic CSF leakage (ICSFL) due to a lumbar puncture. OBJECTIVES: To compare the RICG findings of SIH and ICSFL. METHODS: The presence of direct findings suggesting CSF leakage and indirect findings including early visualization of the bladder and absence of radioactivity over the brain convexities were evaluated in seven SIH and six ICSFL patients. Radioisotope clearance was assessed semi-quantitatively. RESULTS: In contrast to the variety of anatomical levels at which direct findings were detected in the SIH patients, the ICSFL patients only displayed direct findings at the lumbosacral level. None of the ICSFL patients displayed direct findings at 1 hour after the tracer injection. Although early visualization of the bladder was depicted in all patients, no activity was visualized over the brain convexities in the SIH patients. In the semi-quantitative analysis, the tracer retention index at 24 hours was lower in the SIH patients than the ICSFL patients. CONCLUSIONS: The early appearance of direct findings above the lumbosacral level, the absence of radioactivity over the brain convexities and a low tracer retention index are suggestive of SIH.

[Essential Tremor That is Difficult to Improve with Standard Medical Treatment-Suppression: Excluding Surgical Treatment].

For essential tremors that are refractory to standard medical treatment, surgical treatment is considered when there is obstruction in activities of daily living. However, there are patients who do not wish to undergo or are contraindicated for surgical treatment. In this paper, we explored what is considered to be the standard medical treatment and when surgery cannot be performed. In Japan, medical treatment is based on the use of arotinolol and primidone, and combination therapy and second-line drugs are extensively discussed. Furthermore, an algorithm of the treatment for essential tremors in Japan has been provided.

[Adrenoleukodystrophy: Lorenzo's Oil].

Lorenzo's Oil, an American movie released in 1992, is based on a true story of a couple who spare no effort to search for a cure for their 5-year-old son who gradually develops eccentricities and signs of progressive motor and speech disturbances and is diagnosed with adrenoleukodystrophy. Despite lack of medical knowledge, Lorenzo's parents embark on a mission to study the disease on their own and eventually discover a therapeutic mixture referred to as Lorenzo's oil. Most characters in the movie retained real-life names. Even after its release in 1992, the movie has provided some subjects in many ways.

[The Myasthenia Gravis Activities of Daily Living score and associated factors to distinguish the refractory phase in generalized myasthenia gravis patients with 5 years or more disease duration].

Associated factors of the Myasthenia Gravis Activities of Daily Living (MG-ADL) score were investigated in 55 patients who had had generalized MG for more than 5 years. In multivariate analysis, correlates of the MG-ADL score at the last follow-up were the total number of fast-acting treatments (FTs) (standardized regression coefficient 0.617，P < 0.001) and Myasthenia Gravis Foundation of America (MGFA) classification (standardized regression coefficient 0.227，P = 0.032) (F = 32.7，P < 0.001). In patients with a score of 5 or more on MG-ADL at the last follow-up, tendency as follows were seen: 1) early-onset (P = 0.002), 2) longer duration (P = 0.014), 3) high frequency of MGFA classification V (P = 0.017), 4) high frequency of the total number of FTs (P < 0.001), and 5) higher dose of prednisolone at the last follow-up (P = 0.003). MGFA V, early-onset without depending on E-L-T classification, or difficulty of reduction for high doses of prednisolone can be the target of novel treatment for MG, and future prospective study will be expected.

A 36-year-old Man with Repeated Short-term Transient Hyperammonemia and Impaired Consciousness with a Confirmed Carbamoyl Phosphate Synthase 1 Gene Monoallelic Mutation.

A 36-year-old man experienced severely impaired consciousness twice after drinking because of hyperammonemia. No abnormal blood tests were found other than ammonia levels. However, magnetic resonance imaging (MRI) showed atrophy of the brain parenchyma. One the second occasion, the patient suffered severe impairment of consciousness, and because of seizures and glossoptosis, mechanical ventilation was started. Urea cycle disorders (UCDs) were assumed to be involved. Genetic testing revealed a monoallelic mutation of the carbamoyl phosphate synthase 1 (CPS1) gene. When transient hyperammonemia of unknown cause occurs repeatedly in adults, an active investigation for UCDs should be conducted.

Utility of the fluid-attenuated inversion recovery sequence in detecting a hyperintense putaminal rim in multiple system atrophy-parkinsonism: a preliminary study.

OBJECTIVE: To investigate the utility of fluid-attenuated inversion recovery (FLAIR) imaging for diagnosing multiple system atrophy-parkinsonism (MSA-P). METHODS: We retrospectively evaluated 49 subjects (19 with MSA-P including 11 with early-stage disease, 15 with Parkinson's disease and 15 matched controls) in order to compare the diagnostic value of FLAIR imaging to detect a hyperintense putaminal rim (HPR) with that of T(2)-weighted (T2W) imaging. RESULTS: Compared with T2W imaging, FLAIR imaging detected HPR more conspicuously in the 19 MSA-P patients (p = 0.01); this trend was also observed in 11 early-stage MSA-P patients (p = 0.01). Furthermore, FLAIR imaging tended to increase sensitivity of detecting HPR compared with T2W imaging (all patients: 89 vs. 58%, p = 0.07; early-stage patients: 100 vs. 55%, p = 0.06). CONCLUSIONS: FLAIR imaging might be more useful for detecting HPR in MSA-P patients, even though they are at an early stage.

Relationship between 3-O-methyldopa and the clinical effects of entacapone in advanced Parkinson's disease.

The aim of this study is to clarify the relationship between serum 3-O-methyldopa (3-OMD) and the clinical effects of entacapone. The 3-OMD and maximum serum concentration (Cmax) of levodopa were measured in 21 Parkinson's Disease patients who took 100 mg levodopa / dopa decarboxylase inhibitor. After the administration of entacapone, the 3-OMD concentration and percentage of "on" time during waking hours (% of "on" time) were studied for 8 weeks. The 3-OMD concentration was reduced by 34%, and the increase in % of "on" time was 28% at the 8th week compared with baseline. We defined the COMT-index as [baseline 3-OMD concentration] / [levodopa Cmax when 100 mg levodopa was administered alone]. The COMT-index was significantly correlated with the increase in % of "on" time at the 8th week. In conclusion, the measurement of baseline 3-OMD and levodopa pharmacokinetics is useful for predicting the clinical effects of entacapone.

[Clinical characteristics of ischemic stroke in elderly patients with cancer].

AIM: We classified acute ischemic stroke patients with cancer according to their causal relations, and attempted to evaluate the clinical characteristics of ischemic stroke associated with cancer. METHODS: This is a retrospective study of all acute ischemic stroke patients admitted to our hospital between January 2006 and March 2009. Among acute ischemic stroke patients, we identified 30 patients with a history of cancer, or who developed cancer within 1 year from their ischemic stroke onset. There were 2 patients excluded from our evaluation because they had undergone extirpation of their cancer more than 5 years before stroke onset, and no recurrence of cancer within 5 years of stroke onset was noted. Finally, 28 patients were enrolled and evaluated in this study. Ischemic stroke was classified based on the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. In addition, we classified the patients according to their causal relations of ischemic stroke with cancer. RESULTS: The median patient age was 74 years (range, 56 to 91 years); 68% of patients were men. Of these, 8 (29%) were classified into an ischemic stroke related to cancer group. There was a higher prevalence of ischemic stroke related to cancer in patients under 75 years old with clinical stage IV cancer (p=0.02). D-dimer tended to be higher in those patients with ischemic stroke related to cancer in this study (p=0.13). CONCLUSION: Ischemic stroke related to cancer was found more frequently in patients under 75 years old with advanced cancer. Additionally, D-dimer tended to be higher in those patients with ischemic stroke related to cancer.

Idiopathic trigeminal neuropathy with trigeminal mass lesion on MRI: Neoplasm or not?

The objective of the present study was to investigate clinical and magnetic resonance imaging (MRI) features of idiopathic trigeminal neuropathy with transient MR abnormalities mimicking a neoplasm (ITNmn). We retrospectively evaluated clinical and MRI features in two cases of ITNmn seen in our institution in comparison with those of previously reported five cases. The most common symptom was altered facial sensation and numbness limited to one or more trigeminal nerve divisions (100%). ITNmn commonly affected not only the second and third divisions (86% and 57%, respectively) but also the first division (71%). The most common findings on MRI were enlargement and gadolinium enhancement of the trigeminal nerve, which were similar to those seen in neoplasms (100%). The abnormalities spontaneously regressed in all five evaluable cases. ITNmn should be added in the differential diagnosis of non-specific mass-like lesions in trigeminal neuropathy and be observed carefully without surgical treatment.

Usefulness of 3D-PRESTO imaging in evaluating putaminal abnormality in parkinsonian variant of multiple system atrophy.

INTRODUCTION: Principles of echo shifting with a train of observations (PRESTO) sequence has long echo time which emphasizes the effect of T2* relaxation time and contribute to its high sensitivity to the susceptibility change. The aim of our study was to evaluate the ability of 3D-PRESTO sequence in detecting putaminal hypointensity in patients with parkinsonian variant of multiple system atrophy (MSA-P) and in discriminating between MSA-P and Parkinson's disease (PD). METHODS: The signal intensity of the putamen and localization of abnormality were evaluated on 3D-PRESTO, T2*-weighted (T2*W), and T2-weighted (T2W) sequences in ten patients with MSA-P, 14 with PD, and ten controls. The putaminal signal intensity was assessed in all sequences and graded relative to the palladium. Atrophy of the putamen and posterolateral hyperintensity rim on T2W sequence were also evaluated in MSA-P patients. RESULTS: Putaminal hypointensity was more often seen in MSA-P than PD and controls on 3D-PRESTO sequence (p = 0.002) as well as on T2*W sequence (p = 0.003). 3D-PRESTO sequence could reveal lower intensity better than T2*W sequence in four of ten MSA-P cases. Hemi- or bilateral putaminal hypointensity, atrophy, and posterolateral hyperintensity rim were recognized in 90%, 70%, and 70% of ten MSA-P cases, respectively. Three cases revealed hypointensity on 3D-PRESTO sequence without posterolateral hyperintensity rim. Putaminal signal changes occurred in the posterolateral part with a striking lateral to medial gradient in all nine cases with putaminal hypointensity (nine out of nine, 100%). CONCLUSIONS: 3D-PRESTO sequence appears to be useful for depicting putaminal hypointensity in MSA-P patients and in differentiating MSA-P from PD.

[Diagnosis of MSA-P and PSP-P in Early Stage].

Differentiating Parkinson's disease (PD) from multiple system atrophy with predominant parkinsonism (MSA-P) or progressive supranuclear palsy-parkinsonism (PSP-P) in early stages of the disease is extremely difficult. MSA-P and PSP-P are often misdiagnosed as PD. MSA-P and PSP-P may be diagnosed in their early stages by considering clinical symptoms and neuroradiological findings together. Diffusion weighted images, T2* weighted images and proton density weighted images are useful for diagnosis MSA-P in early stages , while the magnetic resonance parkinsonism index is useful tool for diagnosis of PSP-P in the early stage.

A case of systemic lupus erythematosus associated with cerebral arteritis: a case report and case-based literature review.

A 62-year-old female patient with systemic lupus erythematosus (SLE) was admitted for cerebral infarction. The magnetic resonance angiography showed focal narrowing of the cerebral arteries that was initially considered as atherosclerosis due to her cardiovascular risk factors. Ten weeks later, she was again admitted for multiple cerebral infarctions. Vessel wall magnetic resonance imaging revealed gadolinium enhancement of the arterial walls of the narrowing lesions, leading to a diagnosis of cerebral arteritis. Based on a literature review, cerebral medium-sized arteritis in SLE likely progresses insidiously during the active phase of SLE, which may later result in occlusion irrespective of disease activity.

Aseptic meningitis as an initial presentation of Sjögren syndrome: a report of two cases and literature review.

Sjögren syndrome (SS) is one of several collagen vascular diseases that occasionally involve the central nervous system. We report two cases of SS involving young patients who initially presented with aseptic meningitis. A male with recurrent AM was found to have anti-Ro/SSA and La/SSB antibodies in a screening test for autoimmune process. A minor salivary gland biopsy revealed lymphocytic infiltrations compatible with SS, although the patient did not exhibit sicca symptoms. A female presenting with AM and polyarthritis also reported xerophthalmia. Anti-Ro/SSA antibody testing and a positive result in a minor salivary gland biopsy led to the diagnosis of SS. In the literature review, we found that AM or aseptic meningoencephalitis (AME) preceded or had a concomitant onset with SS in approximately 70% of cases. Screening for anti-Ro/SSA antibody, as well as systemic assessment for rheumatic symptoms, may be useful for diagnosing AM/AME of unknown etiology.