Fatal Community-Acquired Clostridioides difficile Infection as a Cause of Listeria Meningitis: A Case Report.

A 77-year-old woman with a history of total gastrectomy was transferred to our hospital with complaints of fever and consciousness disturbance for five days. She had fever and consciousness disturbance with positive meningeal signs. Laboratory findings indicated an elevated inflammatory response and hypoalbuminemia, and computed tomography (CT) of the body indicated intestinal gas retention and mild ascites. Cerebrospinal fluid analysis revealed pleocytosis with elevated protein levels and a diagnosis of Listeria meningitis was made. Treatment with ampicillin/sulbactam was started, and her fever and consciousness disturbance resolved on day 2. However, on day 3, her fever and conscious disturbance deteriorated, and she went into shock subsequently. Laboratory findings revealed deteriorated inflammatory response and hypoalbuminemia. Body CT showed an obvious distended bowel loop and intestinal edema. A stool culture revealed positive Clostridioides difficile toxin B, and we diagnosed her with Clostridioides difficile infection (CDI). Although intravenous metronidazole was initiated, she died due to prolonged hypovolemic shock. We considered she had community-acquired CDI because her CDI emerged immediately after the initiation of antibiotics, symptom deterioration within 48 hours of admission, and abnormal abdominal CT findings at admission. Listeria meningitis can develop based on community-acquired CDI. Because CDI can have a very rapid and fatal course and is sometimes complicated by other infectious diseases, clinicians should pay attention to this complication.

A case of meningoencephalitis caused by multisystem inflammatory syndrome in adult SARS-CoV-2 infection.

A 37-year-old woman was hospitalized with fever and consciousness disturbance. She showed systemic inflammation with stress cardiomyopathy. Brain computed tomography showed diffuse brain edema. Cerebrospinal fluid (CSF) findings revealed markedly elevated cerebrospinal fluid pressure with pleocytosis, elevated protein, and elevated interleukin 6. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nicking enzyme amplification reaction test using a nasopharyngeal swab was positive, and the patient was diagnosed with SARS-CoV-2 infection. From the negative result of the CSF SARS-CoV-2 polymerase chain reaction test and no findings of bacterial or viral infection, we diagnosed meningoencephalitis by multisystem inflammation syndrome in adults (MIS-A). Intravenous methylprednisolone pulse therapy improved her symptoms and brain edema. There have been no cases of MIS-A with meningoencephalitis, and no initial treatment strategy has been established, especially in emergency cases of suspected MIS-A. The present case suggested Early intravenous methylprednisolone pulse with anti-coronaviral therapies after the exclusion of bacterial infection would be useful in suspected MIS-A with emergent meningoencephalitis cases.

Enteral tube nutrition for geriatric post-stroke dysphagia evaluation (ENGE) score to evaluate the risk of dysphagia after acute ischemic stroke.

BACKGROUND: Post-stroke dysphagia (PSD) is a common complication after stroke. Early PSD prediction is essential for patient stratification for intensive oral intake rehabilitation. We aimed to develop a PSD prediction score using clinical data obtained at admission. METHODS: We examined consecutive patients with acute ischemic stroke between 2018 and 2019. The dysphagia status 14 days after admission was assessed using the Functional Oral Intake Scale (FOIS). PSD was defined as FOIS 1-3, which represents tube-dependent nutrition. Using multivariable logistic regression analysis, we constructed the Enteral tube Nutrition for Geriatric post-stroke dysphagia Evaluation (ENGE) score. The discriminative performance of the ENGE score was analyzed by receiver operating curve analysis. The reproducibility of the ENGE score was validated using patient data in 2020. RESULTS: PSD developed in 84 of 488 patients (median age 78 years; 57% males). The ENGE score ranged from 0 to 6, with 1 point assigned for older age (≥78 years), 1 for high premorbid modified Rankin Scale (mRS) (≥1), 3 for high NIHSS score (≥12), and 1 for low serum albumin (<3.0 mg/dl). The area under the curve (AUC) of the ENGE score for discriminating PSD was 0.88 (95% confidence interval [CI] 0.83-0.92), and a score of 3 or more had a higher positive likelihood ratio. In the validation cohort, the AUC of the ENGE score for PSD was 0.85 (95% CI 0.78-0.91), which was similar to the derivation cohort (p = 0.491). CONCLUSIONS: The ENGE score predicts severe PSD after acute ischemic stroke with good reproducibility.

Eustachian Valve-Enhanced Paradoxical Cerebral Embolism: A Case Report.

Cryptogenic stroke includes many suspicious embolic causes that do not fulfill the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification criteria. Atrial fibrillation (AF) is one of the major hidden causes of cryptogenic stroke, and an implantable loop recorder (ILR) is widely used for detecting AF. Herein, we report a case of paradoxical cerebral embolism due to a large Eustachian valve with large PFO under no molecular complete remission (CR) of acute monocytic leukemia (AMoL). A 75-year-old man arrived at our emergency room because of aphasia and right hemiparesis. He had a history of two cryptogenic strokes and implanted ILR. Magnetic resonance imaging showed left middle cerebral artery occlusion with slight acute ischemic lesion. The red clot was retrieved by mechanical thrombectomy, and complete recanalization was achieved. We checked ILR, but there was no AF. Transesophageal echocardiography revealed a large patent foramen ovale (PFO) and the large Eustachian valve in the right atrium. Although obvious deep vein thrombosis (DVT) was not detected in venous ultrasonography of the lower extremities, Wilms' tumor 1 messenger ribonucleic acid (WT1mRNA) expression level was high, and AMoL was considered to be not in molecular CR, suggesting a high risk of thrombosis to the large Eustachian valve. From large PFO and no molecular CR of AMoL, we diagnosed him with paradoxical cerebral embolism. Ruling out of AF by ILR and other etiologies, such as aortic or carotid atherosclerosis and pulmonary shunt, also supported the diagnosis of paradoxical cerebral embolism. Even in the absence of obvious DVT, paradoxical cerebral embolism should be considered in cases of a large Eustachian valve and PFO with a hypercoagulable state.

Geriatric nutrition risk index predicts prolonged post-stroke dysphagia in acute ischemic stroke.

BACKGROUND: Post-stroke dysphagia (PSD) is a common complication after stroke. Malnutrition inhibits stroke recovery and is associated with stroke mortality. However, no studies have investigated the effects of nutritional state at admission on prolonged PSD. METHODS: We retrospectively analyzed ischemic stroke patients in our institute from January 2018 to December 2020. Swallowing function was assessed using the Food Oral Intake Scale; prolonged PSD was defined as levels 1-3 at 14 days after admission. The Geriatric Nutritional Risk Index (GNRI) was used to assess nutritional risks, which were classified as follows: >98, no nutritional risk; 92-98, mild nutritional risk; 82-92, moderate nutritional risk; and <82, severe nutritional risk. The association between GNRI and prolonged PSD was assessed. RESULTS: Of 580 patients (median age, 81 years; male, 53%), prolonged PSD was detected in 117 patients. Patients with severe dysphagia had older age, higher pre-stroke modified Rankin Scale score, lower GNRI, and higher National Institutes of Health Stroke Scale score. Logistic regression analysis revealed that lower GNRI was independently associated with prolonged PSD (continuous value; adjusted odds ratio [OR] 1.03, 95% confidence interval [CI] 1.00-1.05). In addition, when "severe" and "moderate" nutritional risk was analyzed as a single class, moderate or severe nutritional risk (GNRI < 92) was independently associated with prolonged PSD (adjusted OR 2.50, 95% CI 1.29-4.87), compared with no nutritional risk patients (GNRI > 98). CONCLUSIONS: In acute ischemic stroke, lower GNRI at admission was independently associated with prolonged PSD, suggesting that GNRI at admission might identify patients at risk of prolonged PSD.

A Case Report of Deep Cerebral Venous Thrombosis Presenting Unilateral Lesion: The Association of Asymmetric Venous Outflow and Unilateral Lesion.

A 60-year-old man was admitted to our hospital due to progressive aphasia and right hemiparesis. Brain magnetic resonance imaging showed the left thalamus and basal ganglia lesion. Digital subtraction angiography showed the vein of Galen and straight sinus occlusion, suggesting cerebral venous thrombosis. Since his left transverse sinus was hypoplastic, his left deep cerebral lesion was due to the left deep cerebral vein congestion by the asymmetrical venous outflow. After anticoagulant therapy, his symptom and unilateral lesion improved. Clinicians should consider the vein of Galen and straight sinus thrombosis even in unilateral deep cerebral lesions.

Rapid Evaluation of Large Vessel Occlusion for Mechanical Thrombectomy Using Carotid Duplex Ultrasound.

Objectives This study clarified the usefulness of carotid duplex ultrasound (CDU) in evaluating large vessel occlusion (LVO) in patients with acute stroke planned to be treated with mechanical thrombectomy (MT). Methods This study was single-center, prospective, observational trial. If the ratio of end-diastolic velocity in the common carotid arteries was ≥1.4, or diastolic flow in the affected internal carotid artery (ICA) was absent on CDU, patients were immediately transferred to the angio-suite without additional cerebrovascular imaging. Clinical parameters, including time metrics and outcomes, were evaluated in participants. Patients We enrolled stroke patients with a National Institutes of Health Stroke Scale score ≥6 and Alberta Stroke Program Early CT score ≥6 in whom MT could be initiated within 6 hours of the stroke onset. Results Among 140 patients screened during the study period, 48 were ultimately enrolled. Twenty-seven patients were diagnosed with LVO by CDU alone. CDU offered 83% sensitivity and 82% specificity for identifying the occlusion of the ICA or M1 segment of the middle cerebral artery. Among the 29 total patients treated with MT, 20 (67%) showed a modified Rankin Scale score ≤2 at 90 days. The door-to-puncture time was significantly shorter in patients evaluated by CDU alone (34 minutes) than in those evaluated by magnetic resonance angiography after CDU (47.5 minutes, p<0.001). Conclusion CDU might reduce the time metrics for early initiation of MT with good sensitivity and specificity in identifying LVO.

Steroid Rebound Phenomenon as a Cause of Delayed Cerebral Vasospasm in Post-Splenectomy Pneumococcal Meningitis: A Case Report.

Pneumococcal meningitis as an overwhelming post-splenectomy infection (OPSI) has a higher risk of neurological complications and is sometimes life-threatening. In acute pneumococcal meningitis, four days of dexamethasone is widely used for the prevention of neurological complications. Herein, we report a 68-year-old woman with the diagnosis of pneumococcal meningitis as OPSI. With adequate antibiotics and dexamethasone, her symptoms gradually improved. However, after dexamethasone withdrawal, her consciousness got worse and got into a coma. Brain magnetic resonance imaging revealed acute cerebral infarctions in the bilateral middle cerebral artery territory with multiple vascular stenoses and hydrocephalus. Vascular stenoses improved by follow-up, suggesting cerebral vasospasm. There were no suggestive findings of cerebral vasculitis. Follow-up cerebrospinal fluid analysis showed remained pleocytosis with no bacteria, which could not suggest meningitis recurrence. Since steroid therapy was rapidly withdrawn, we diagnosed that the cerebral vasospasm was due to the steroid rebound phenomenon. The steroid rebound phenomenon due to the excessive immune response to bacterial microstructures has been reported in pneumococcal meningitis. Especially, the present case was asplenia and the usual dexamethasone use would not adequately suppress the immune response to bacterial microstructures. Since pneumococcal meningitis as OPSI has a higher risk of neurological complications, clinicians should consider longer and more cautious steroid tapering.

Uremic Encephalopathy Presenting with Unilateral Destructive Leukoencephalopathy Successfully Treated with Hemodialysis.

An 81-year-old woman was hospitalized with progressive consciousness disturbance. Blood tests showed acidemia with severe renal dysfunction, and a cerebral spinal fluid (CSF) test showed pleocytosis with myelin basic protein (MBP) elevation. Brain magnetic resonance imaging showed unilaterally dominant subcortical white matter lesions with lentiform fork sign on T2-weighted imaging. After initiating hemodialysis, her consciousness disturbance and white matter lesions improved, suggesting uremic encephalopathy (UE). Unilaterally dominant leukoencephalopathy and high pleocytosis with MBP elevation in CSF are less common than previously identified characteristics of UE. When unilateral leukoencephalopathy occurs in patients with renal failure, UE should be considered.

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease With False-Positive Results in SARS-CoV-2 Antigen Tests: A Case Report.

A 23-year-old man presented with headache, fever, and urinary retention. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen tests were positive, but SARS-CoV-2 polymerase chain reaction (PCR) results were negative. MRI showed long spinal cord lesions. Due to positive serum and cerebrospinal fluid myelin oligodendrocyte glycoprotein (MOG) antibodies, we made the diagnosis of MOG-associated disease. We concluded that the antigen tests were false positives because SARS-CoV-2 IgM and IgG were not elevated. Although the mechanism behind the false-positive results is unclear, physicians should consider the possibility of a false-positive result in the SARS-CoV-2 antigen test.

Progressive Small Vessel Disease Burden as a Diagnostic of Central Nervous System-Restricted Microscopic Polyangiitis: A Case Report and Review of the Literature.

Microscopic polyangiitis (MPA) is a type of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis linked to myeloperoxidase (MPO), usually accompanied by pulmonary and renal lesions. MPA sometimes causes central nervous system (CNS) involvement such as cerebral infarction. Herein, we report a case of a 72-year-old man with a headache. He had an unknown cause of the elevated inflammatory response. Magnetic resonance imaging (MRI) showed multiple cerebral infarctions in the small vessel region in the right basal ganglia with multiple cerebral microbleeds (cMBs). After admission, his left hemiparesis and consciousness disturbance gradually deteriorated. A follow-up MRI on day 18 showed increased multiple cerebral infarctions in small vessel regions with increased cMBs. Additional blood tests revealed positive MPO-ANCA. Although there were no findings suggestive of active renal or pulmonary involvement or peripheral neuropathy, we diagnosed him as having MPA-associated CNS-restricted vasculitis. CNS involvement of MPA is relatively rare but is associated with a high small vessel disease (SVD) burden. In addition to the unknown cause of inflammatory response, the multiple cMBs increase and a short-term recurrence of cerebral infarctions in the bilateral thalamus and basal ganglia was the clue for the diagnosis of CNS-restricted vasculitis. It is difficult to diagnose MPA vasculitis when lesions are restricted to the CNS. In the absence of lesions other than SVD, MPA-associated CNS vasculitis should be suspected in patients with progressive SVD burden and elevated inflammatory response.

Prognostic factors for acute ischemic stroke in patients undergoing hemodialysis.

BACKGROUND: Acute ischemic stroke (AIS) is a critical complication in patients undergoing dialysis. Although the improvement of AIS management is an urgent requirement, few studies have evaluated the prognostic factors of AIS in these patients. This study aimed to assess the relationship between clinical factors in patients undergoing dialysis and the prognosis of AIS. METHODS: Among 1267 patients who were hospitalized for AIS in Sendai City Hospital from January 2015 to June 2020, 81 patients undergoing hemodialysis were retrospectively enrolled. Multivariate analysis was performed to evaluate the effect of baseline characteristics, dialysis factors, and neurological severity of patients at admission [National Institutes of Health Stroke Scale (NIHSS) score] on in-hospital mortality, physical disability, and the need for rehabilitation transfer. RESULTS: A higher NIHSS score was a critical risk factor for each outcome and the only significant factor for in-hospital mortality [odds ratio (OR)/point 1.156, 95% confidence interval (CI) 1.054-1.267]. The risk factors of physical disability were NIHSS score (OR/point 1.458, 95% CI 1.064-1.998), older age (OR/year 1.141, 95% CI 1.022-1.274), diabetic nephropathy (OR 7.096, 95% CI 1.066-47.218), and higher premorbid modified Rankin scale (mRS) score (OR/grade 2.144, 95% CI 1.155-3.978); while those of rehabilitation transfer were a higher NIHSS score (OR/point 1.253, 95% CI 1.080-1.455), dialysis vintage (OR/year 1.175, 95% CI 1.024-1.349), and intradialytic hypotension before onset (OR 5.430, 95% CI 1.320-22.338). CONCLUSIONS: Along with neurological severity, dialysis vintage, intradialytic hypotension, and diabetic nephropathy could worsen the prognosis of patients with AIS undergoing hemodialysis.

Clinicopathologic Features of Oculopharyngodistal Myopathy With LRP12 CGG Repeat Expansions Compared With Other Oculopharyngodistal Myopathy Subtypes.

Importance: Repeat expansion of CGG in LRP12 has been identified as the causative variation of oculopharyngodistal myopathy (OPDM). However, to our knowledge, the clinicopathologic features of OPDM with CGG repeat expansion in LRP12 (hereafter referred to as OPDM_LRP12) remain unknown. Objective: To identify and characterize the clinicopathologic features of patients with OPDM_LRP12. Design, Setting, and Participants: This case series included 208 patients with a clinical or clinicopathologic diagnosis of oculopharyngeal muscular dystrophy (OPDM) from January 1, 1978, to December 31, 2020. Patients with GCN repeat expansions in PABPN1 were excluded from the study. Repeat expansions of CGG in LRP12 were screened by repeat primed polymerase chain reaction and/or Southern blot. Main Outcomes and Measures: Clinical information, muscle imaging data obtained by either computed tomography or magnetic resonance imaging, and muscle pathologic characteristics. Results: Sixty-five Japanese patients with OPDM (40 men [62%]; mean [SD] age at onset, 41.0 [10.1] years) from 59 families with CGG repeat expansions in LRP12 were identified. This represents the most common OPDM subtype among all patients in Japan with genetically diagnosed OPDM. The expansions ranged from 85 to 289 repeats. A negative correlation was observed between the repeat size and the age at onset (r2 = 0.188, P = .001). The most common initial symptoms were ptosis and muscle weakness, present in 24 patients (37%). Limb muscle weakness was predominantly distal in 53 of 64 patients (83%), but 2 of 64 patients (3%) had predominantly proximal muscle weakness. Ptosis was observed in 62 of 64 patients (97%), and dysphagia or dysarthria was observed in 63 of 64 patients (98%). A total of 21 of 64 patients (33%) had asymmetric muscle weakness. Aspiration pneumonia was seen in 11 of 64 patients (17%), and 5 of 64 patients (8%) required mechanical ventilation. Seven of 64 patients (11%) developed cardiac abnormalities, and 5 of 64 patients (8%) developed neurologic abnormalities. Asymmetric muscle involvement was detected on computed tomography scans in 6 of 27 patients (22%) and on magnetic resonance imaging scans in 4 of 15 patients (27%), with the soleus and the medial head of the gastrocnemius being the worst affected. All 42 muscle biopsy samples showed rimmed vacuoles. Intranuclear tubulofilamentous inclusions were observed in only 1 of 5 patients. Conclusions and Relevance: This study suggests that OPDM_LRP12 is the most frequent OPDM subtype in Japan and is characterized by oculopharyngeal weakness, distal myopathy that especially affects the soleus and gastrocnemius muscles, and rimmed vacuoles in muscle biopsy.

Carotid web leads to new thrombus formation: computational fluid dynamic analysis coupled with histological evidence.

Carotid web has been recognized as a rare cause of ischemic stroke with high recurrence rate. We describe a 48-year-old woman with carotid web who developed embolic stroke. We obtained a fresh thrombus from the internal carotid artery when carotid endarterectomy was performed. A preoperative computational fluid dynamics (CFD) study showed stagnation of blood around the web structure as well as the low wall shear stress. The rheological analysis newly disclosed mechanisms of thrombus formation related to the carotid web. CFD study in the carotid web may determine indication and timing of surgical interventions with further accumulation of clinical evidence.

Supratentorial infarcts accompanying hiccup.

BACKGROUNDS: The main culprit lesion causing hiccup in patients with ischemic stroke is thought to involve the medulla oblongata, but some cases of hiccups caused by damage to the supratentorial cortex have been reported. The present study aimed to address the clinical and radiological characteristics of acute stroke patients accompanied by hiccups caused by supratentorial lesions. METHOD: We retrospectively studied 5,309 consecutive patients with acute ischemic stroke or transient ischemic attack who were admitted to our institute within 7 days after onset between April 2006 and September 2017. We searched for the term "hiccup" in prospectively collected descriptive datasets and analyzed associations between hiccup and clinical and radiological findings, with particular focus on patients with supratentorial lesions. RESULTS: We finally selected 16 stroke patients accompanied by hiccup. Nine patients had infarcts in the lateral medulla oblongata, and others had supratentorial infarcts (three patients with cortical infarcts, four patients with subcortical infarcts). Moreover, the right hemisphere was frequently damaged in this series (6/7, 86%). CONCLUSIONS: Hiccup could be caused by supratentorial infarcts including the insular cortex, temporal lobe, and subcortex.

Phased changes in strategies can reduce delay of intravenous thrombolysis administration to 15 min.

OBJECTIVES: The present study aimed to determine whether phased changes in strategies including the Helsinki model affect the delay of intravenous thrombolysis (IVT) using tissue plasminogen activator (tPA) to treat acute ischemic stroke. METHOD: We retrospectively studied 516 consecutive patients treated with IVT in our department between October 2005 and December 2018. We implemented a system of hospital pre-notification in 2005, when IVT was initially implemented at our center. We then improved the IVT strategy by simplifying brain imaging (July 2011), premixing tPA (April 2014), locating a blood cell counter in the emergency room (June 2015), manually administering a tPA bolus before preparing a continuous infusion (January 2016), awarding a prize to members of the acute stroke team (November 2016), and completing registration before arrival and sending patients directly to computed tomography (February 2017). We analyzed the effects of these strategic changes on annual median door-to-needle times (DTN). RESULTS: The DTN was annually reduced, from a median of 90 [interquartile range, 55-98] minutes in 2006 to 15 [12-24.25] minutes in 2017. By 2017, 94% of patients were treated within 60 min of arrival. Multivariate logistic regression analysis revealed that initial NIHSS score ≤ 4 (OR 2.67, 95% CI 1.3-5.7) and anticoagulation before onset (OR 6.00, 95% CI 2.47-14.58) were independently associated with 20 min or more of DTN in 186 patients treated from 2016 to 2018. CONCLUSIONS: Phased strategic change to reduce the delay in delivering IVT reduced median DTN to 15 min at a single Japanese stroke center.

Early neurosyphilis presenting with multiple cranial nerve palsies: A case report of management by combined penicillin-corticosteroid treatment.

Early neurosyphilis commonly appears in basilar meninges, and its meningeal inflammation can spread to neighboring cranial nerves, resulting in some cranial nerve palsies. Herein, we report a case of a 51-year-old man who presented with right peripheral facial nerve palsy. His symptoms completely disappeared with prednisolone monotherapy without antibiotics use and were not exacerbated during clinical treatment. However, 2 months after remission of seventh cranial neuropathy, fifth and eighth cranial neuropathies appeared on the right side. Serologic tests for syphilis were revealed to be abnormal. Finally, the patient was diagnosed with early neurosyphilis with multiple cranial palsies. His neurological symptoms were markedly improved by combined penicillin-corticosteroid treatment. Systemic corticosteroids could be effective as adjunctive therapy to ameliorate neurological sequelae in early neurosyphilis.

Seasonal Variations in Neurological Severity and Outcomes of Ischemic Stroke　- 5-Year Single-Center Observational Study.

BACKGROUND: Seasonal variations in the severity and outcomes of stroke remain unclarified.Methods and Results:A total of 2,965 acute ischemic stroke patients from a single-center prospective registry were studied. Among the total patients, stroke onset did not vary by season, though it varied with a peak in winter when limited to patients >75 years old (P=0.026), when limited to patients with moderate-to-severe initial neurological deficits (National Institutes of Health Stroke Scale Score ≥10, P=0.014), and when limited to those with cardioembolic stroke (n=1,031, P=0.010). In 1,934 patients with noncardioembolic stroke, stroke onset did not vary by season. After multivariable adjustment, moderate-to-severe neurological deficits were more common in winter (odds ratio 1.37, 95% confidence interval 1.10-1.72) and spring (1.27, 1.01-1.60), and death at 1 year was more common in summer than in fall (1.55, 1.03-2.36); death or dependency (modified Rankin Scale score 3-6) and death or bedridden (score of 5-6) were not differently common among the seasons. CONCLUSIONS: Overall ischemic stroke showed a fairly even distribution among the 4 seasons. Cardioembolic stroke was more common in winter. Ischemic stroke patients had more moderate-to-severe initial neurological deficits in winter and spring. Poor clinical outcomes at 1 year were generally similar among the seasons. Ischemic stroke is not necessarily a winter-dominant disease.

GNE myopathy associated with congenital thrombocytopenia: a report of two siblings.

GNE myopathy is an autosomal recessive muscular disorder caused by mutations in the gene encoding the key enzyme in sialic acid biosynthesis, UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE/MNK). Here, we report two siblings with myopathy with rimmed vacuoles and congenital thrombocytopenia who harbored two compound heterozygous GNE mutations, p.V603L and p.G739S. Thrombocytopenia, which is characterized by shortened platelet lifetime rather than ineffective thrombopoiesis, has been observed since infancy. We performed exome sequencing and array CGH to identify the underlying genetic etiology of thrombocytopenia. No pathogenic variants were detected among the known causative genes of recessively inherited thrombocytopenia; yet, candidate variants in two genes that followed an autosomal recessive mode of inheritance, including previously identified GNE mutations, were detected. Alternatively, it is possible that the decreased activity of GNE/MNK itself, which would lead to decreased sialic content in platelets, is associated with thrombocytopenia in these patients. Further investigations are required to clarify the association between GNE myopathy and the pathogenesis of thrombocytopenia.