Absence of diffusion-weighted imaging abnormalities in a patient with neuronal intranuclear inclusion disease.

INTRODUCTION: Herein, we report a genetically confirmed case of neuronal intranuclear inclusion disease without characteristic subcortical hyperintensities on diffusion-weighted imaging. CASE PRESENTATION: A 75-year-old man was admitted to our hospital with subacute onset of conscious disturbance. Except for gastric cancer, he had no apparent past medical or family history. He presented with transient fever, vomiting, and urinary retention. On admission, no apparent abnormal intensity was detected on diffusion-weighted imaging. The symptoms improved within 10 days, without any medical treatment. Additional inspections were performed under suspicion of neuronal intranuclear inclusion disease. Intranuclear inclusions were found not only from skin biopsy but also from his stomach specimens, which had been resected 6 years previously. Subsequent genetic testing revealed repeat expansion of GGC amplification in NOTCH2NLC. CONCLUSION: Characteristic neuroimaging and skin biopsy findings are important clues for diagnosing neuronal intranuclear inclusion diseases. Nonetheless, confirming a diagnosis is difficult due to the diversity of clinical manifestations and radiological features. Clinicians should suspect neuronal intranuclear inclusion disease in patients with transient encephalitic episodes, even if no abnormalities are detected on diffusion-weighted imaging.

Quantitative arterial spin labeling magnetic resonance imaging analysis of reversible cerebral vasoconstriction syndrome: A case series.

OBJECTIVE: This study aimed to quantify chronological cerebral blood flow (CBF) changes using arterial spin labeling (ASL) magnetic resonance imaging in patients with reversible cerebral vasoconstriction syndrome (RCVS). BACKGROUND: Quantitative ASL analyses in RCVS have not been well described in the literature. METHODS: Quantification of ASL using an automated region-of-interest placement software and a 5-point visual scale of vasoconstriction severity was performed in five RCVS patients. The association between CBF changes and RCVS-related complications was evaluated. RESULTS: Quantitative ASL revealed variable patterns of decreasing CBF in the first week, followed by subsequent increases. Notably, arterial vasoconstriction paradoxically progressed despite an increase in CBF from the first to the second week; this increase was relatively higher in patients with both cortical subarachnoid hemorrhage and posterior reversible encephalopathy syndrome. CONCLUSIONS: Quantitative ASL revealed that CBF initially decreased and subsequently increased, especially in the second week. These changes may serve as surrogate imaging markers for RCVS-related complications, and could further contribute to understanding the pathology of RCVS.

First case report of fungal meningitis due to a polypore mushroom Irpex lacteus.

A 73-year-old Japanese man with a medical history of sarcoidosis was diagnosed with meningitis caused by an undetermined fungus. For further identification, the cerebrospinal fluid sample was analyzed for the rDNA internally transcribed spacer regions, and the fungus was identified as Irpex lacteus. I. lacteus is classified under phylum Basidiomycota and is a wood-rotting bracket mushroom. Although there is no standard treatment regimen for I. lacteus infections, amphotericin B was effective in this patient. Herein, we present, to our knowledge, the first reported case of fungal meningitis caused by I. lacteus, its treatment course, and review relevant published literature.

[Thoracoscopic Plication for Congenital Diaphragmatic Eventration in an Adult].

Thoracoscopic plication for congenital diaphragmatic eventration in an adult. Diaphragmatic eventration is known to be abnormal elevation of diaphragm and congenital causes are due to abnormal diaphragm muscle development. Here we report surgical treatment of congenital diaphragmatic eventration. A 45-year-old woman who complained of cough was admitted to our hospital. She had history of cough and was diagnosed as diaphragmatic eventration in childhood. Chest X-ray showed elevated left hemidiaphragm with a bowel gas underneath. Under the diagnosis of congenital eventration of left hemidiaphragm, plication of the left diaphragm by video-assisted thoracoscopic surgery (VATS) was performed. One month after surgery, severe cough disappeared completely.

Multiple Border-Zone Infarcts Triggered by Influenza A Virus Infection in a Patient With Cerebral Autosomal Dominant Arteriopathy Presenting With Subcortical Infarcts and Leukoencephalopathy.

Patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) can develop multiple border-zone infarcts due to hypotension, hypovolemia, or surgery. We report the case of a 41-year-old woman with CADASIL who developed multiple border-zone infarcts due to influenza A virus infection. The patient had no apparent history or episode of stroke or altered consciousness following the onset of respiratory symptoms, which were due to the influenza A infection. Diffusion-weighted magnetic resonance images of the brain showed multiple acute-phase infarcts in border-zone areas of both cerebral hemispheres and the corpus callosum; fluid-attenuated inversion-recovery magnetic resonance images showed increased signal in the subcortical areas of both temporal poles. Gene analysis identified a heterozygous mutation c.160C>T in exon 2 of the NOTCH3 gene (p.Arg54Cys). A diagnosis of CADASIL was established. Our case demonstrates that infectious conditions such as influenza A can trigger multiple border-zone infarctions in patients with CADASIL.

Importance of Chronological Changes on High-Resolution Vessel Wall Imaging for Diagnosis of Isolated Anterior Cerebral Artery Dissection.

INTRODUCTION: The accurate diagnosis of isolated anterior cerebral artery dissection (iACA-D) is made difficult by the spatial resolution on conventional magnetic resonance imaging (MRI) techniques including time-of-flight magnetic resonance angiography that is too limited to detect minute arterial wall abnormalities. Recent advances in high-resolution vessel wall imaging (HRVWI), which can detect intramural hematomas (IMH), have improved the noninvasive diagnostic accuracy of iACA-D. However, despite the risk of overlooking minute IMH and aneurysmal dilations especially at the early disease stage, the utility of T1-weighted and T2-weighted HRVWI at each disease stage (i.e., acute, early subacute, late subacute and chronic) has not been evaluated thoroughly enough. This prompted us to undertake the present study to determine the diagnostic value of chronological changes of IMHs on T1-weighted HRVWI and arterial dilations on T2-weighted HRVWI to achieve the earliest possible and most accurate diagnosis of iACA-D. METHODS: In addition to six patients with iACA-D, five previously reported iACA-D patients from three institutions for whom reliable information on HRVWI and its examination date was available were enrolled in this study. IMHs on T1-weighted HRVWI and aneurysmal dilations on T2-weighted HRVWI and their chronological changes were visually evaluated. RESULTS: Either or both of IMHs on T1-weighted HRVWI and aneurysmal dilations on T2-weighted HRVWI were detected in all our six patients and the five previously reported ones. The disease stage showed a notable influence on the degree of their visualization. In contrast to IMHs which are regarded as the gold standard for the diagnosis of intracranial dissections, aneurysmal dilations were identified in 80% of cases even at the acute stage, reaching 100% at the early subacute stage. Despite the excellent detection rate of IMHs at the late subacute stage (100%), their detectability is poor at the acute and early subacute stages (0 and 40%, respectively). CONCLUSION: The results of this study highlighted the importance of aneurysmal dilations on T2-weighted HRVWI as a diagnostic marker to raise suspicion of iACA-D at the acute and early subacute stages, and similarly IMHs on T1-weighted HRVWI to confirm the diagnosis of iACA-D at the late subacute stage. These stage-dependent detectability changes in IMHs and aneurysmal dilations make an understanding of the chronological changes of these abnormal imaging findings mandatory to achieve an early and accurate diagnosis of iACA-D.

Multifaceted structural magnetic resonance imaging findings in demented patients with pathologically confirmed TDP-43 proteinopathy.

This short report clarifies the heterogeneity of structural magnetic resonance imaging (MRI) findings in seven demented patients due to pathologically accumulated TAR DNA-binding protein-43 (TDP-43) protein using visual analyses including visual rating scales (i.e., global cortical atrophy and medial temporal atrophy scales). In addition to the well-known frontotemporal lobar atrophy, structural MRI has revealed multifaceted imaging findings including asymmetric atrophy of the frontoparietal lobe and cerebral peduncle, midbrain atrophy, and localized or diffuse white matter T2 hyperintensity. Understanding of these multifaceted neuroimaging findings is important for the precise antemortem diagnosis of TDP-43 proteinopathy.

Machine learning-based screening for outpatients with dementia using drawing features from the clock drawing test.

Background and Objectives: In geriatrics and dementia care, early diagnosis is crucial. We developed a dementia screening model using drawing features from clock drawing tests (CDT) and investigated the features contributing to the discrimination of dementia and its screening performance. Methods: This study included 129 older adults attending a dementia outpatient clinic. We obtained information on the diagnosis of dementia and CDT data from medical records and quantified 12 types of drawing features according to the Freedman scoring system. Based on the dementia diagnosis information, participants were assigned to two groups: 58 in the dementia diagnosis group and 71 in the non-diagnosis group. Using Boruta, an iterative feature selection algorithm, and a support vector machine, a machine learning method, we analyzed the drawing features contributing to dementia discrimination and evaluated discrimination performance. Results: Five types of drawing features were selected as contributors to discrimination, including "numbers in the correct position," "minute target number indicated," and "hand in correct proportion." These features exhibited a discriminating sensitivity of 0.74 ± 0.16 and specificity of 0.74 ± 0.18 for detecting dementia. Conclusion: This study demonstrated a method for identifying individuals likely to be diagnosed with dementia among patients attending a dementia outpatient clinic using drawing features. The knowledge of drawing features contributing to dementia differentiation may assist healthcare practitioners in clinical reasoning and provide novel insights for clinical practice. In the future, we plan to develop a primary screening for dementia based on machine learning using CDT.

A case of autoimmune encephalitis in a patient with a solitary intracranial plasmacytoma.

A 65-year-old woman presented with fever and abnormal behavior. Magnetic resonance imaging showed swelling of the left medial temporal lobe and an intracranial extra-axial occipital tumor. While her neurological symptoms improved after the administration of corticosteroid therapy under the suspicion of autoimmune encephalitis, the occipital tumor unexpectedly shrank, and the diagnosis of a solitary plasmacytoma was confirmed by biopsy. Additional examinations revealed elevated anti-glutamate receptor antibodies in the cerebrospinal fluid. The patient was diagnosed with autoimmune encephalitis concurrent with an intracranial solitary plasmacytoma. Central nervous system involvement can be considered a neurological complication in patients with a solitary plasmacytoma.

[Changes in vessel wall magnetic resonance contrast-enhancement in a patient with multiple cerebral infarction due to meningovascular neurosyphilis].

A 46-year-old man with a history of generalized skin rash following physical contact with possible syphilis infection developed right upper and lower extremity ataxia and right lower extremity paresis. Brain magnetic resonance (MR) imaging revealed multiple areas of acute cerebral infarction mainly within the territories of the right superior cerebellar artery (SCA) and left anterior cerebral artery. The patient was diagnosed with meningovascular neurosyphilis based on positive results on syphilis testing of the serum and cerebrospinal fluid. MR angiography revealed decreased signal intensity in the proximal segment of the right SCA, and gadolinium-enhanced three-dimensional T1-weighted MR images showed an enhancement of the vessel wall in this segment of the artery. Signal intensity in the right SCA showed partial improvement following the completion of intravenous penicillin treatment, and contrast enhancement of the vessel wall disappeared simultaneously with clinical improvement. Alterations in cerebral vessel walls on contrast-enhanced MR imaging in cases of meningovascular neurosyphilis may reflect vascular inflammatory activity.

[Anti-voltage-gated potassium channel (VGKC) complex/leucine-rich glioma-inactivated protein 1 (LGI1) antibody-associated limbic encephalitis mimicking dementia with Lewy bodies in a patient with subacute REM sleep behavior disorder].

A 73-year-old woman was admitted to our hospital owing to abnormal diurnal behavior, sudden brief episodes of impaired awareness, and loud nocturnal sleep talking. Her symptoms had developed gradually over several months and had been treated as dementia with Lewy bodies (DLB) at another clinic. Video-polysomnography revealed brief sleep talking and gross movements associated with REM sleep without atonia. 18F-FDG PET revealed increased glucose metabolism in both medial temporal lobes. These findings led to a diagnosis of limbic encephalitis (LE) comorbid with REM sleep behavior disorder (RBD). After two courses of intravenous methylprednisolone pulse therapy, her symptoms gradually improved. Her illness was later confirmed as anti-voltage-gated potassium channel (VGKC) complex/leucine-rich glioma-inactivated protein 1 (LGI1) antibody-associated LE using serum analyses. Clinical features of anti-VGKC complex/LGI1 antibody-associated LE can mimic those of DLB, particularly when comorbid with RBD.

[Transient changes in food preference in a patient with cerebellar infarction].

A 44-year-old woman was admitted to our hospital due to dizziness and ataxia of the trunk and right upper limb. Brain MRI revealed an acute infarct lesion in the right posterior inferior cerebellar artery territory. In addition to the cognitive deterioration observed in the subacute phase, a change was noted in her food preference-from light-tasting, low-caloric Japanese cuisine, sugarless coffee, and hot drinks to strong-tasting, high-caloric Western cuisine, sugar-rich coffee, and iced drinks. Single-photon emission computed tomography showed hypoperfusion in the bilateral frontal lobes and right cerebellum. These cognitive and food preference-related changes were gradually restored over six months after the onset. The reduced cerebral blood flow in the bilateral frontal lobes also restored along with the clinical improvement, with the maximal changes in the bilateral subcallosal areas. This case suggests that changes in food preference can occur as a symptom of cerebellar infarction, possibly by the mechanism similar to cerebellar cognitive affective syndrome.

Multiple system atrophy variant with severe hippocampal pathology.

The striatonigral and olivopontocerebellar systems are known to be vulnerable in multiple system atrophy (MSA), showing neuronal loss, astrogliosis, and alpha-synuclein-immunoreactive inclusions. MSA patients who displayed abundant neuronal cytoplasmic inclusions (NCIs) in the regions other than the striatonigral or olivopontocerebellar system have occasionally been diagnosed with variants of MSA. In this study, we report clinical and pathologic findings of MSA patients characterized by prominent pathologic involvement of the hippocampus. We assessed 146 consecutively autopsied MSA patients. Semi-quantitative analysis of anti-alpha-synuclein immunohistochemistry revealed that 12 of 146 patients (8.2%) had severe NCIs in two or more of the following areas: the hippocampal granule cells, cornu ammonis areas, parahippocampal gyrus, and amygdala. In contrast, the remaining 134 patients did not show severe NCIs in any of these regions. Patients with severe hippocampal involvement showed a higher representation of women (nine women/three men; Fisher's exact test, p = 0.0324), longer disease duration (13.1 ± 5.9 years; Mann-Whitney U-test, p = 0.000157), higher prevalence of cognitive impairment (four patients; Fisher's exact test, p = 0.0222), and lower brain weight (1070.3 ± 168.6 g; Mann-Whitney U-test, p = 0.00911) than other patients. The hippocampal granule cells and cornu ammonis area 1/subiculum almost always showed severe NCIs. The NCIs appeared to be ring-shaped or neurofibrillary tangle-like, fibrous configurations. Three of 12 patients also had dense, round-shaped NCIs that were morphologically similar to pick bodies. The patients with Pick body-like inclusions showed more severe atrophy of the medial temporal lobes and broader spreading of NCIs than those without. Immunohistochemistry for hyperphosphorylated tau and phosphorylated TDP-43 revealed minimal aggregations in the hippocampus of the hippocampal MSA patients. Our observations suggest a pathological variant of MSA that is characterized by severe involvement of hippocampal neurons. This phenotype may reinforce the importance of neuronal alpha-synucleinopathy in the pathogenesis of MSA.

Heterozygous Cysteine-sparing NOTCH3 Variant p.Val237Met in a Japanese Patient with Suspected Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy.

A 64-year-old Japanese man with recurrent cerebral ischemic events and cognitive impairment was suspected of having cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) because of a family history and brain magnetic resonance imaging findings of cerebral white matter hyperintensities. The cysteine-sparing variation p.Val237Met was identified in NOTCH3. An intensive skin biopsy showed negative results (no granular osmiophilic material or positive NOTCH3 immunostaining), suggesting that the patient's definite diagnosis and pathogenicity of p.Val237Met were uncertain. We additionally reviewed previous reports of two Japanese families with p.Val237Met.

Severe Measles Encephalitis and Acute Disseminated Encephalomyelitis in an Immunocompetent Japanese Young Male.

Measles encephalitis rarely affects young adults and has no established treatment strategy. This brief report described the rare case of an immunocompetent 30-year-old man with severe measles pneumonia and encephalitis, following the autoimmune disease acute disseminated encephalomyelitis, during a large measles outbreak in 2018 in Japan. With multidisciplinary treatments, including corticosteroids, intravenous immunoglobulins, vitamin A, and therapeutic plasma exchange, the patient was successfully treated. This case provides a new strategy for treating measles encephalitis and its complications during measles outbreak.

[Confusional migraine in a young adult female: Is it a subtype of migraine with aura?]

A 22-year-old female was admitted to our hospital due to acute onset of severe headache, confusion, and deterioration of consciousness. Results of initial examinations did not suggest cerebrovascular diseases, encephalitis, or nonconvulsive status epilepticus. Over the next several weeks, her level of consciousness fluctuated in parallel with the severity of headache. The electroencephalogram, recorded during a symptomatic episode, showed lack of posterior dominant rhythm, and the single-photon emission CT (SPECT) also revealed a decrease in cerebral blood flow predominantly in the occipital lobes. Administration of sodium valproate and topiramate, recommended as treatment for migraine, dramatically ameliorated her headache and consciousness. Although this was an adult-onset case, her symptoms and clinical course were similar with the diagnosis of ICHD-3-unlisted confusional migraine rather than other listed subtypes of migraine with aura. Further accumulation of similar adult-onset cases is necessary to clarify the nature of this illness.

Utility of T2-weighted high-resolution vessel wall imaging for the diagnosis of isolated posterior inferior cerebellar artery dissection at acute and early subacute stages.

Recent advances in magnetic resonance high-resolution vessel wall imaging (HRVWI), which can detect intramural hematomas (IMH), improve the noninvasive diagnostic accuracy of isolated posterior inferior cerebellar artery dissection (iPICA-D). However, despite the risk of overlooking minute IMH, the utility of T2-weighted HRVWI has not been thoroughly evaluated. This study aimed to compare the utility of T2-weighted HRVWI with that of T1-weighted HRVWI, basiparallel anatomical scanning (BPAS), and magnetic resonance angiography (MRA) for the diagnosis of iPICA-D mainly in the acute and early subacute stages in 6 iPICA-D patients (three acute, two early subacute and one late subacute stages on initial examinations). Dissection-related abnormalities included IMH on T1-weighted HRVWI, aneurysmal dilations on T2-weighted HRVWI and discrepancy between BPAS and MRA. On initial examinations, T2-weighted HRVWI revealed iPICA-D-related abnormalities more conspicuously than did T1-weighted HRVWI and combination of BPAS and MRA. Except in a single case with a discrepancy between the outer contour on BPAS and inner contour on MRA, no specific abnormalities were detected besides T2-weighted HRVWI at acute or early subacute stages. In addition to T1-weighted HRVWI, BPAS and MRA, T2-weighted HRVWI should be performed to diagnose acute and early subacute iPICA-D.

[Multiple mononeuropathy associated with systemic sclerosis with vasculitis confirmed by nerve biopsy: a case report].

A 68-year-old woman with a medical history of interstitial pneumonia associated with systemic sclerosis (SSc) presented with numbness of the lower limbs and left drop foot. She was diagnosed with multiple mononeuropathy based on the laterality of her symptoms, muscle weakness, thermal hypoalgesia, and nerve conduction study findings. Left sural nerve biopsy showed vasculitis, and steroid therapy was effective. This case highlights the importance of histopathological assessment to select an appropriate treatment strategy.

[Intrasellar xanthogranuloma with abscess formation in a patient with Rathke's cleft cyst].

An 80-year-old woman diagnosed with granulomatosis with polyangiitis (GPA) complained of a sustained, non-pulsatile headache. Her brain MRI diffusion-weighted images revealed a high-signal-intensity, space-occupying lesion in the sellar region that was rim-enhanced on gadolinium-enhanced T1-weighted images. Pituitary involvement of GPA was initially suspected based on her condition; however, an abscess formation within an existing Rathke's cleft cyst was also considered according to a previous MRI finding that had been conducted for an unrelated purpose. A trans-sphenoidal resection of the lesion revealed an abscess with foam cells. These findings were consistent with a diagnosis of a xanthogranuloma with abscess formation in the Rathke's cleft cyst, and her headache was completely resolved without any immune therapy that is required for GPA. Thus, differential diagnosis of space-occupying lesions in the seller region should include xanthogranuloma with abscess formation, especially if a Rathke's cleft cyst is detected as an antecedent finding.