Ramsay-Hunt syndrome and subsequent sensory neuropathy as potential immune-related adverse events of nivolumab: a case report.

BACKGROUND: Nivolumab is an immune checkpoint inhibitor (ICI) and is used for the treatment of advanced non-small cell lung cancer (NSCLC). Several immune-mediated neurological adverse events associated with ICIs have been reported to date, such as Guillain-Barré syndrome. Nivolumab-associated neurological adverse events can vary, and their etiology remains unclear. CASE PRESENTATION: A 72-year-old man with NSCLC was treated with nivolumab as a second-line therapy. After 13 rounds of nivolumab therapy, he presented with Ramsay-Hunt syndrome (RHS) followed by acute ataxic sensory neuropathy. Antiviral therapy for Varicella-Zoster virus and prednisolone resulted in partial improvement of RHS, while almost no recovery was observed in the sensory neuropathy. However, the sensory ataxia significantly improved after intravenous immunoglobulin (IVIg) therapy, and interestingly, the facial palsy associated with RHS also improved. The neurological manifestations, nerve conduction study result, and imaging findings supported that dorsal root ganglia were the primary lesion site of acute ataxic sensory neuropathy. CONCLUSIONS: Our case presented with the comorbidity of RHS and subsequent ataxic sensory neuropathy after nivolumab therapy to whom IVIg was effective. Our case suggested the wide variability of possible neurological symptoms, and the potential usefulness of IVIg to sensory ataxic neuropathy, seen in cancer patients with ICI treatment.

A Case Study of Transductive Resolution: Analyzing the Practice of Inclusive Education for a Girl with down's Syndrome at an Elementary School in Japan.

Inclusive education is a process in which schools devise curricula and plan resource allocation to include the diverse group of children in society. Although not many schools promote inclusive education at a school-wide level, there are some schools making efforts toward inclusion in Japan. This study aimed to understand the process of inclusion in a Japanese elementary school by using Trajectory Equifinality Modeling. We conducted a participant observation and focused on Naomi, who was 7 years old and had Down's syndrome. Naomi spent more than 80% of her time in the general education classroom, where she began to refuse to do tasks different from other children. In regard to this, the opinions of the homeroom teacher and the coordinator of these classes were completely different, but their opposing opinions were transformed into complementary ones using time differentiation, and they were able to continue to collaborate toward inclusive education. We found "transductive resolution" as a key to understanding the processes of striving for inclusive education.

Paraneoplastic Polymyositis Due to Renal Cell Carcinoma in a Patient with Autosomal Dominant Polycystic Kidney Disease.

We herein report a 70-year-old man with malaise and muscle weakness that had developed within a month. The patient also had abdominal fullness due to polycystic kidney disease. Severe proximal skeletal muscle weakness and mild elevation of creatinine kinase to 301 IU/L were noted. A muscle biopsy of the right bicep showed polymyositis. Computed tomography showed a right renal mass, and an analysis after right nephrectomy identified clear cell carcinoma. The muscle weakness subsided one month after nephrectomy and intravenous immunoglobulin therapy. Therefore, we suspect that the development of polymyositis in this patient was closely related to renal cell carcinoma.

Cholesterol crystal embolism-related cerebral infarction: Magnetic resonance imaging and clinical characteristics.

BACKGROUND AND AIMS: Cholesterol crystal embolism-related cerebral infarction (CCE-CI) is frequently misdiagnosed due to the lack of specific symptoms. To aid in differential diagnosis, this study comprehensively characterized the magnetic resonance imaging (MRI) and clinical manifestations of CCE-CI and compared these features to those of atherothrombotic cerebral infarction (ACI). METHODS: This single-center, retrospective, observational study was conducted at Kitasato University Hospital, Kanagawa, Japan. We identified 37 clinically or histopathologically confirmed CCE-CI cases and 110 ACI cases treated from January 2006 to May 2020. Groups were compared for mean age, sex ratio, clinical presentations, imaging manifestations, precipitating factors, comorbid conditions, medications, and smoking history. RESULTS: Of 37 eligible patients with CCE-CI, 10 (27.0%) received brain MRI, of which 8 (21.6%) exhibited high-intensity signals indicative of brain lesions on diffusion-weighted imaging (DWI). However, two patients with DWI lesions exhibited no detectable neurological abnormalities. Patients with CCE-CI frequently demonstrated bilateral DWI lesions involving the bilateral anterior and posterior circulation, a pattern absent in ACI (50% vs. 0%, p < 0.001). Compared to patients with ACI, CCE-CI patients also demonstrated significantly lower estimated glomerular filtration rate (p < 0.001) as well as more frequent eosinophilia (p = 0.006), atherosclerotic plaques ≥4-mm thick in the ascending aorta or proximal arch (p = 0.001), and aortic aneurysm (p < 0.001). CONCLUSIONS: Patients with CCE-CI develop multiple DWI lesions across several vascular territories, even in the absence of neurological symptoms. Comorbid aortic aneurysm may increase CCE-CI risk. These findings could help in the differential diagnosis of CCE-CI.

Clinical features of opticospinal multiple sclerosis with anti-aquaporin 4 antibody.

BACKGROUND: We have followed 9 Japanese patients with opticospinal multiple sclerosis (OSMS), some of whom showed longitudinally extensive spinal cord lesions, deep sensory disturbances and resistance to treatment. We investigated the patients for anti-aquaporin 4 (AQP4) antibodies and related this to their neuroimaging, clinical and laboratory features. METHODS: We studied the clinical course, neurological findings, cerebrospinal fluid (CSF), and electrophysiological findings, and determined the presence of anti-AQP4 antibody and human leukocyte antigen DPB1 and DRB1 alleles. RESULTS: Five patients (56.6%) had anti-AQP4 antibody. Antibody-positive patients displayed female predominance, longitudinally extensive spinal cord lesions, higher frequency of exacerbations, severe disability, and higher cell counts and total protein content without IgG oligoclonal bands in the CSF. They also showed poor steroid responsiveness and poor therapeutic response to interferon beta(1b). CONCLUSIONS: The presence of anti-AQP4 antibodies correlates with clinical severity and poor prognosis in OSMS.

Longus Colli Tendinitis in a Patient Presenting with Neck Pain and Acute Systemic Inflammation.

The diagnosis of longus colli tendinitis (LCT) is sometimes challenging, especially when laboratory data show marked inflammation and neuroimaging studies do not indicate calcification within the tendon of the longus colli muscles. We herein report a case of LCT that presented with elevated inflammation parameters without calcification on imaging. Findings characteristic of LCT, such as prevertebral hyperintensity areas on T2-weighted images and no signs of purulent diseases, informed our diagnosis of LCT. Enhanced computed tomography and magnetic resonance imaging are useful procedures when diagnosing LCT after ruling out other critical purulent diseases.

[Case of opticospinal multiple sclerosis showing phenotype change to conventional type induced by interferon beta-1b].

A 57-year-old woman who had severe opticospinal multiple sclerosis (OSMS) was admitted to our hospital. She had presented with visual loss and gait disturbance at the age of 48, and had since experienced more than 10 relapses and been hospitalized 9 times. Interferon beta-lb treatment (8,000,000 units on alternate days) had been started at her last admission. Prior to the present admission, she had developed left visual loss and gait difficulty after headache lasting a few days. Cerebrospinal fluid showed elevation of cell count (322/mm3), protein (130 mg/dl), and myelin basic protein (462 pg/ml; normal, <102 pg/ml). On examination, she exhibited decreased left visual acuity, paraplegia, ataxia of the right upper extremity, and sensory disturbance, particularly in the lower extremities. Bowel and bladder disturbances were also evident Laboratory testing showed lymphocytopenia (420/microl), compared to a white cell count of 1700/microl just before initiation of interferon beta-lb1therapy. MRI revealed a new lesion in the cerebellum in addition to small T2-hyperintense lesions in the white matter of the brain;these had been noted previously. Interferon beta-1b therapy was ceased and she was treated using methylprednisolone pulse therapy. After the abnormal findings resolved, however, interferon beta-lb1therapy was restarted. Three months after, she exhibited right hemiparesis without facial palsy concurrent with lymphocytopenia. MRI showed T2-hyperintense lesions in the periventricular white matter, left cerebral peduncle, bilateral middle cerebellar peduncles, and right cerebellar hemisphere. We reduced the doses of interferon beta-lb1immediately. Thereafter, she did not have relapse for 29 months, but her EDSS (expanded disability status scale) has not recovered. Although interferon beta-lb1has been recognized as an effective drug for decreasing the relapse rate and severity of both secondary progressive MS and relapsing-remitting MS, the present case showed the possibility of interferon beta-1b being associated with phenotype change from OSMS to conventional MS (CMS).

[Two cases of idiopathic carotid-cavernous fistula with headache and ophthalmoplegia].

We report two cases of idiopathic carotid-cavernous fistula (CCF) with primary symptoms of headache and diplopia. A 47-year-old woman presented with throbbing headache in her right frontal region followed by right trochlear nerve palsy. Brain magnetic resonance imaging (MRI) was normal but magnetic resonance angiography (MRA) and computed tomographic angiography (CTA) revealed abnormal signals around the right cavernous sinus. CCF was diagnosed by conventional angiography. The symptoms improved naturally but after about 1 year she suddenly exhibited conjunctival congestion. A 41-year-old man complained of fluctuating headache with sudden left abducens nerve palsy. MRI and MRA were normal but CTA showed abnormal signals around the left cavernous sinus. A final diagnosis of CCF was made by conventional angiography and he was transferred to another hospital for stereotactic radiosurgery. Diagnosis of CCF tends to be delayed in cases presenting with only headache and external ophthalmoplegia. However, CCF with cortical vein drainage can lead to cerebral hemorrhage and early correct diagnosis is needed. Our cases showed a dilated superior ophthalmic vein in enhanced CT and an abnormal signal around the cavernous sinus in CTA. Therefore, CTA may be useful as a relatively non-invasive method that can provide diagnostic clues for CCF.

Internal Carotid Artery Occlusion in Systemic Lupus Erythematosus as a Potential Mimicker of Multiple Sclerosis.

The diagnosis of neurological symptoms in patients with systemic lupus erythematosus (SLE) is often challenging, in part because they sometimes mimic features of multiple sclerosis (MS). Herein we report a case of a young female who presented with relapsing-remitting symptoms of unilateral visual loss and motor aphasia. Additionally, radiological findings revealed multiple white matter lesions on her brain that led to an initial diagnosis of MS based on the established diagnostic criteria. However, she was eventually diagnosed with neuropsychiatric SLE (NPSLE) presenting with extracranial internal carotid artery (ICA) occlusion. Her ICA occlusion had not been detected for 2 months until she underwent magnetic resonance angiography. Although exact underlying pathological mechanisms are unclear, both the ICA occlusion and MS-like brain white matter lesions could be attributed to SLE. This case demonstrated that both of these lesions can coexist in the same patient, suggesting that NPSLE with ICA occlusion can be a potential mimicker of MS, and vice versa. Care must be paid to avoid delay in the diagnosis.

Steakhouse Syndrome in Myotonic Dystrophy.

A 70-year-old man with myotonic dystrophy (MD) showed repetitive vomiting and decreased food ingestion. These symptoms were caused by acute mass of steak impaction occluding the esophagus, known as "steakhouse syndrome," which may have occurred in response to esophageal functional changes following gastrointestinal involvement due to MD pathology. The occluding food was successfully removed endoscopically, and his symptoms resolved without relapse. Our case suggests that MD patients can present with "steakhouse syndrome" due to bolus food impaction occluding the esophagus as one of their gastrointestinal manifestations, which underscores the need for its consideration in MD patients presenting with similar symptoms.

Cefepime-induced encephalopathy in end-stage renal disease patients.

OBJECTIVES: Impaired renal function is a risk factor for cefepime (CFPM)-induced encephalopathy (CFPMIE) in patients treated with CFPM; dose-titration to renal function is recommended to prevent CFPMIE. However, available evidence on the incidence of CFPMIE or preventive efficacy of dose adjustment against CFPMIE in end-stage renal disease (ESRD) patients is limited. METHODS: Single-centre, retrospective observational study. We reviewed consecutive in-hospital adult patients treated with adjusted-dose of CFPM in the period between September 2012 and September 2016, and assessed the CFPMIE in ESRD patients treated with adjusted-dose of CFPM. RESULTS: Out of 422 eligible patients, 6 patients (1.4%) were diagnosed with CFPMIE. The incidence of CFPMIE in ESRD patients was 7.5% (5/67). Among ESRD patients, pre-existing central nervous system (CNS) morbidity was significantly associated with the risk of CFPMIE. CFPMIE occurred in ESRD patients regardless of daily dose, and even with 0.5g/day of CFPM. CONCLUSIONS: Pre-existing CNS morbidity may be associated with an increased risk of CFPMIE in ESRD patients. No significant association was observed between CFPM dose and incidence of CFPMIE in ESRD patients, and future investigation on the safer dose-adjustment strategy in ESRD patients is required for achieving balance between successful infectious treatment and reducing CFPMIE.

Somatosensory evoked potential in neurosyphilis.

Since the development of effective antibiotic therapy, the occurrence of neurosyphilis has become less frequent. The number of syphilitic patients is gradually increasing as a complication in acquired immunodeficiency syndrome, but the diagnosis of neurosyphilis sometimes is difficult. We describe six patients with neurosyphilis and an analysis of their tibial nerve somatosensory evoked potentials. Four of them, including two with no tabes dorsalis symptoms, had delayed P15-N21 or the absence of N21. These abnormalities were ameliorated by treatment for syphilis. Analysis of tibial nerve SEPs provides a useful tool for the diagnosis of neurosyphilis and the evaluation of the extent to which neurosyphilis has progressed.

Therapeutic factors causing hallucination in Parkinson's disease patients, especially those given selegiline.

Selegiline protects nigral dopaminergic neurons and is recommended for the treatment of patients in the early stage of Parkinson's disease (PD). We treated 112 PD patients and noted that those given selegiline had a high incidence of hallucination. Our objective was to determine which clinical therapeutic factors cause such hallucinations. The Kruskal-Wallis and chi-square test showed that in 94 patients, the severity of the hallucinations was significantly related to the duration of illness, Hoehn and Yahr stage, doses of levodopa and cabergoline, whether or not selegiline was used, and whether or not medication for constipation was required. In addition, patients who were treated with a low dose of levodopa (< or =300 mg/day), who had a low Hoehn and Yahr stage, and a short duration of illness (< or =8 years) together with a high dose of selegiline or cabergoline also tended to have hallucinations. MRI findings were not related to the incidence of hallucination. When selegiline is given to patients who have PD of long duration and a high Hoehn and Yahr stage, and who already are receiving levodopa and a dopamine agonist, the doses of levodopa and the dopamine agonists given, as well as the presence of constipation, may be related to the incidence of hallucination.

[A case of dementia with motor neuron disease associated with agraphia--the omission of kana letters].

We report a 55-year-old right-handed Japanese man with motor neuron disease and dysgraphia of kana letters. He was admitted to our hospital because of dysarthria and dysphasia. On admission, the results of general physical examination were within normal limits. Neurological examination revealed severe dysarthria, dysphasia, impaired movement of the tongue without fasciculation and slight distal muscle weakness in the bilateral upper limbs. There were no fasciculation of the muscle. Deep tendon reflexes were hyperactive without Babinski's signs. Sensation, coordination, and gait were normal. Neurophysiological studies demonstrated normal motor nerve conduction velocities and sensory action potential. The results of needle electromyography of the upper limbs were compatible with motor neuron disease (MND). Magnetic resonance imaging (MRI) showed atrophy of the bilateral temporal region of the brain. 99mTc-HMPAO SPECT (Single Photon Emission Computed Tomography) showed reduced uptake of tracer in the bilateral temporal region. On neuropsychological examination, his behavior was normal, and orientation and intelligence were also preserved, but his speech was severely impaired. Reading comprehension was slightly impaired. In regard to writing comprehension, he had no difficulty in copying of words though dictation was found to be impaired. He omitted one kana letter in a word. Agraphia is accompanied by various factors such as aphasia, dementia, agnosia, alexia. But in this case at least for early stage, agraphia existed without other higher cortical dysfunction. He did not show severe dementia in his early stage of his disease, but developed it later in the disease's progression. In this case, agraphia might be due to the atrophic changes in the temporal lobe.

A rat model of Urtica ferox neuropathy.

A species of stinging nettle, Urtica ferox, is indigenous to New Zealand and has caused deaths in animals and humans. We previously reported a human case of acute polyneuropathy due to U. ferox stings. We developed an experimental animal model of U. ferox toxin neuropathy to determine its neurophysiological and pathological characteristics. Male Wistar rats received either normal saline or fluid from U. ferox trichomes by injection into the epineurium of the left sciatic nerve. Neurophysiological and histological studies were carried out 5, 14 and 28 days after administration. Toxin-injected rats developed paresis of the left leg by 14 days with recovery by 28 days. Compound muscle action potentials amplitudes on the left side of toxin-administered rats at day 14 were significantly reduced compared to the right uninjected side. Toxin-injected nerves at days 5 and 14 showed a reduction in the number of myelinated fibres compared to the saline-injected nerves and frequency distributions of myelinated fibres showed a shift to smaller fibres. U. ferox neurotoxin thus produced a transient neuropathy in rat peripheral nerves with neurophysiological and pathological features suggestive of axonopathy. The identity and mechanism of action of the toxin responsible for neuropathy are uncertain.

Ganglioside complexes as new target antigens in Guillain-Barré syndrome.

Antibodies specific for a complex of gangliosides GD1a and GD1b (GD1a/GD1b) were found in sera from eight of 100 patients with Guillain-Barre syndrome (GBS) by the use of enzyme-linked immunosorbent assay and thin-layer chromatogram immunostaining. Those sera also had antibody activities to such ganglioside complexes as GD1a/GM1, GD1b/GT1b, and GM1/GT1b but had little or no reactivity to the each isolated antigen. Clustered epitopes of the ganglioside complex in the plasma membrane may be targeted by such an antibody, and interaction between the antibody and ganglioside complex may induce the neuropathy.