[A case of myopathy, myocarditis, and encephalitis with nonconvulsive status epileptics after immune checkpoint inhibitor therapy for ureter cancer].

A 72-year-old man, who had received pembrolizumab of immune checkpoint inhibitor (ICI) over 6 months for ureter cancer, developed progressive skeletal muscle weakness, dysarthria, dyspnea, and consciousness disturbance over the past two weeks. The systemic work-up tests documented an encephalitis, myopathy, and myocarditis. Multiple autoimmune antibodies of anti-Tr, anti-titin, anti-kv1.4, anti-GM1 and anti-GD1a were positive in the serum. Although myopathy and myocarditis responded to high-dose steroid pulse therapy, encephalopathy deteriorated. Electroencephalogram showed a fluctuated pattern of rhythmic delta activity with fast waves, and a rapid response to intravenous diazepam revealed a condition of nonconvulsive status epileptics (NCSE). The patient had an uneventful course after anti-epileptic medication. The ICIs therapy may trigger a broader activation of multiple autoimmune mechanisms. When an encephalitis by immune-related adverse events does not respond to standard immunotherapy, NCSE may be a main pathophysiological mechanism, thereby anti-epileptics being an alternative treatment option.

Anti-Ma2-Associated Limbic Encephalitis after Termination of Immune Checkpoint Inhibitor Therapy for Malignant Pleural Mesothelioma.

Neurological adverse events of immune checkpoint inhibitor (ICI) therapy mostly develop within 3 months after initiation of ICI treatment. An 82-year-old male with malignant pleural mesothelioma developed anti-Ma2-associated limbic encephalitis at a delay of 18 months after the start of nivolumab therapy (3 months after termination of a 15-month course of ICI treatment). Immunotherapy with steroids and immunoglobulins resulted in moderate neurological improvement. Over the next year, malignant pleural mesothelioma gradually worsened, while the anti-Ma2 antibody test remained positive. Anti-Ma2 paraneoplastic encephalitis may occur after a delay following the discontinuation of ICI therapy.

[A case of adult-onset type II citrullinemia triggered by entering a nursing home with a good response to medium-chain triglyceride oil therapy].

A 49-year-old woman with intellectual disability and a food preference for fried chicken entered a nursing home. After nursing home diet, she developed episodic attacks of hyperammonemic encephalopathy. Her characteristic food preference and the negative results for brain and liver imaging studies suggested urea cycle disorder. A high plasma citrulline level on amino acid analysis and a genetic test for citrine gene confirmed a citrine deficiency (adult-onset type II citrullinemia). Although a low-carbohydrate diet was insufficient, a combination therapy of a low-carbohydrate diet and a medium-chain triglyceride (MCT) oil was effective. MCT oil may be a promising treatment option.

Adult-onset Krabbe disease presenting with an isolated form of peripheral neuropathy.

INTRODUCTION: Adult-onset Krabbe disease is clinically rare and usually affects the pyramidal tracts in the central nervous system. Patients develop a spastic gait, and peripheral neuropathy sometimes occurs simultaneously. METHODS: A 55-year-old woman with consanguineous parents developed slowly progressive, asymmetric muscle weakness and atrophy in her forearms, while her ability to walk remained unaffected without pyramidal tract signs after onset at age 51 years. RESULTS: Nerve conduction studies demonstrated an asymmetric demyelinating-type peripheral neuropathy, and sural nerve biopsy documented reduced myelinated nerve fiber density with uniformly thin myelin sheaths, suggesting hypomyelination. Brain MRI demonstrated minor white-matter injury along the optic radiations, which was associated with asymptomatic, mild, prolonged latency on visual evoked potentials. Laboratory analysis documented low enzyme activity of galactocerebrosidase (GALC) and a known mutation of the GALC gene. CONCLUSION: Isolated peripheral neuropathy occurs very rarely in adult-onset Krabbe disease. Muscle Nerve 54: 152-157, 2016.

Intravenous tissue plasminogen activator for an ischemic stroke with occult double primary cancer.

BACKGROUND: In patients with advanced-stage cancer, systemic thrombolysis with tissue plasminogen activator (tPA) for hyperacute ischemic stroke is not strictly off-label, but it is at higher risk of complications (including bleeding). CASE REPORT: A 71-year-old male with unrecognizable malignancy developed a hemispheric ischemic stroke and received intra-venous tPA within 4.5 h of onset, followed by anticoagulation treatment after 24 h of throm-bolysis. Two days later, the patient had tarry stool and progressive anemia, receiving a blood transfusion. The systemic workup documented the presence of double primary cancers with advanced stage gastric and rectal cancers, and the patient subsequently received palliative care. The outcome at 3 months was a modified Rankin Scale of 5, and the patient died 6 months after the stroke. DISCUSSION: Although systemic thrombolysis with tPA for ischemic stroke in patients with advanced-stage cancer may be performed relatively safely, optimal post-thrombolysis management is important to prevent the complications.

[Cervical retro-odontoid pseudo-tumor treated with posterior decompression surgery].

A cervical retro-odontoid pseudo-tumor, which is considered as a reactive fibrocartilaginous mass, is a rare condition in cervical myelopathy. A 63-year-old male, with repeated neck axial movements by a long-term leisure-time cycling, developed subacute myelopathy. Cervical MRI showed a mass lesion at the retro-odontoid region, compressing to the upper spinal cord. After detailed systemic and local examinations that ruled out primary or metastatic malignancy and inflammatory disorders such as rheumatoid arthritis or chronic kidney diseases, a retro-odontoid pseudo-tumor was diagnosed clinically. The patient underwent posterior C1-laminectomy without tumor resection and its pathological confirmation. After the surgery, his neurological signs of cervical myelopathy improved, and a follow-up MRI one year later showed a mild reduction of the tumor size. The neuro-physicians should recognize the relatively benign pseudotumor in cervical myelopathy, because the tumor size usually shows no further enlargement or regression only after decompression surgery without tumor resection.

[Endogenous endophthalmitis and meningo-encephalitis in septic bacteremia of Klebsiella pneumoniae].

Endogenous endophthalmitis may be a rare condition in acute meningo-encephalitis. A 69-year-old compromised adult abruptly developed septic bacteremia and meningo-encephalitis by Klebsiella pneumoniae. After an improvement from initial conscious disturbance and systemic inflammatory unstable vital conditions by treatment of intensive antibiotic medications, severe unilateral endogenous endophthalmitis with impaired visual acuity was diagnosed by detailed ophthalmological assessments and it deteriorated rapidly. After early vitreous surgery with anti-biotic direct injection, the patient successfully regained visual acuity of 20/200. Among the organisms of endogenous bacterial endophthalmitis, Klebsiella pneumoniae is the worst pathogen mostly resulting in vision loss or enucleation despite any aggressive treatments. The neuro-physicians should recognize the presence of refractory endophthalmitis by Klebsiella pneumoniae, even if clinically asymptomatic, because prompt ophthalmologic diagnosis and managements may improve the outcome.

[Dropped head plus syndrome; a case report].

We reported a patient with so-called "dropped head plus syndrome", a non-progressive myopathy characterized by striking neck extensor weakness followed by progressive limb weakness which is well controlled by azathioprine. This 74-year-old man complained of neck and shoulder fatigue followed by progressive neck extensor weakness over 7 months. On physical examination, neck extensor strength was 4/5 on the MMT scale, but the remainder of the neurological examination and blood tests were normal. Needle EMG showed myopathic changes in the right trapezius and biceps brachialis muscles. Without any treatment, he developed weakness of upper and lower limb muscles about 8 months later, and Gowers' sign was positive. Blood test and needle EMG was unchanged. Muscle biopsy of the left trapezius, deltoid and supraspinatus muscles disclosed nonspecific myopathic changes consisting of variation in fiber size with disorganized intermyofibrillar networks in all the fibers, and there were rimmed vacuoles in some fibers of the deltoid muscle. There was no change on corticosteroids, but there was a dramatic improvement with azathioprine and his muscle symptoms disappeared. We, therefore, made the diagnosis of "dropped head plus syndrome". This appears to be the first such case in Japan.