Neurologic disorders associated with anti-glutamic acid decarboxylase antibodies: A comparison of anti-GAD antibody titers and time-dependent changes between neurologic disease and type I diabetes mellitus.

To determine clinical features of neurologic disorders associated with anti-glutamic acid decarboxylase antibodies (anti-GAD-Ab), we examined titers and time-dependent changes of anti-GAD-Ab. Six patients, stiff person syndrome (2), cerebellar ataxia (1), limbic encephalitis (1), epilepsy (1), brainstem encephalitis (1), were compared with 87 type I diabetes mellitus (T1DM) patients without neurologic disorders. Anti-GAD-Ab titers and index were higher in neurologic disorders than in T1DM, suggesting intrathecal antibody synthesis. Anti-GAD-Ab titers in T1DM decreased over time, whereas they remained high in neurologic disorders. Immunotherapy improved neurological disorders and anti-GAD-Ab titers and index provide clinically meaningful information about their diagnostic accuracy.

Refractory Cryptococcus neoformans Meningoencephalitis in an Immunocompetent Patient: Paradoxical Antifungal Therapy-Induced Clinical Deterioration Related to an Immune Response to Cryptococcal Organisms.

We present a case of refractory Cryptococcus neoformans meningoencephalitis in an immunocompetent woman. Her clinical symptoms did not improve with 6 months of antifungal therapy, and MRI abnormalities, indicating severe meningeal and cerebral inflammation, persisted despite a decreasing cryptococcal antigen titer. The patient continued to deteriorate despite antifungal therapy, and her condition clearly improved following treatment with adjunctive corticosteroid. We postulate that the paradoxical antifungal therapy-related clinical deterioration was due to an immune response to cryptococcal organisms, which responded to corticosteroids. These observations provide rationale for a further evaluation of corticosteroids in the management of select cases of C. neoformans central nervous system infection.

Fear of hypoglycemia and its determinants in insulin-treated patients with type 2 diabetes mellitus.

The aim of the present study was to investigate the prevalence of fear of hypoglycemia, in association with severe hypoglycemia and social factors, in insulin-treated patients with type 2 diabetes mellitus. A questionnaire survey on hypoglycemia and patient-physician communication was carried out in 355 patients with insulin-treated type 2 diabetes mellitus patients at 16 hospitals and clinics. A fear of hypoglycemia was reported by 27.7% of patients. A stepwise logistic regression analysis found that severe hypoglycemia during the past 1 year was a significant determinant of fear of hypoglycemia (odds ratio 2.16, 95% confidence interval 1.06-4.41; P = 0.034), and age (odds ratio 1.02, 95% confidence interval 1.00-1.05, P = 0.038) and living alone (odds ratio 1.93, 95% confidence interval 1.00-3.73, P < 0.05) were significantly higher in patients with fear of hypoglycemia than in those without it.

[Multiple cerebral infarctions in a patient with Churg-Strauss syndrome: A case report].

We report the case of a 65-year-old woman who presented with Churg-Strauss syndrome (CSS) associated with multiple cerebral infarcts. Four years ago, she was diagnosed as having CSS based on asthma, hypereosinophilia and peripheral neuropathy, and corticosteroid therapy achieved a remission. However, she showed exacerbation of asthma and hypereosinophilia during the tapering schedule of steroid, and she was hospitalized because of dizziness and mild left side weakness. Analysis of blood chemistry detected significant hypereosinophilia (13,730/µl), increased blood-coagulating activity, elevated NT-proBNP concentration and renal dysfunction. MRI of the brain revealed multiple small infarcts in cortex and the watershed area. The patient was diagnosed with exacerbation of CSS, and treatment with increased dose of corticosteroid induced a clear improvement in symptoms, with decrease of the eosinophilia and a clear improvement of the renal function. The hypercoagulable state and direct eosinophil toxicity may contribute to strokes in hypereosinophilic condition of CSS. This case was remarkable for illustrating multiple cerebral infarctions in CSS. CSS should always be considered in patients with hypereosinophilia and stroke.

Glucagon underutilized among type 1 diabetes mellitus patients in Japan.

AIM: Glucagon is recommended to treat severe hypoglycemia in nonhospital environments, when a patient with type 1 diabetes mellitus (T1DM) is unconscious and unable to eat or drink. However, the actual possession rate of glucagon in Japan has not been investigated. SUBJECTS AND METHODS: We recruited 208 T1DM patients older than 15 years of age. The patients were treated at 16 hospitals and clinics in different regions of Japan. Answers were obtained using a self-administered questionnaire about the possession, the experience of usage, and the preference to possess glucagon after reading what is glucagon and when it is used. A stepwise logistic regression analysis was performed to assess the influence of various factors on the possession of glucagon. RESULTS: The possession rate of glucagon was 15.9%, and the rate of those who had experience of using glucagon to treat severe hypoglycemia was 6.0%. The rate of preference to possess glucagon at home after reading the description of glucagon was 39.0%. The possession of glucagon was significantly associated with results of the Glucagon Knowledge Test (odds ratio=24.1; 95% confidence interval, 3.2-183.3; P=0.002) and the history of severe hypoglycemia within 1 year (odds ratio=4.8; 95% confidence interval, 2.0-12.0; P=0.001). CONCLUSIONS: Glucagon as a measure to treat severe hypoglycemia was underutilized among T1DM patients in Japan.

The Relation of Urinary 8-OHdG, A Marker of Oxidative Stress to DNA, and Clinical Outcomes for Ischemic Stroke.

BACKGROUND: Oxidative stress/free radical generation after ischemic stroke contributes to neuronal cell injury. We evaluated the utility of an oxidative stress marker, urinary 8-hydroxy-2-deoxyguanosine (8-OHdG), to demonstrate an association between the changes of 8-OHdG and outcomes after acute ischemic stroke. METHODS: We enrolled 44 patients (26 males and 18 females) who visited our hospital due to acute ischemic stroke. Urine was collected on admission and on Days 7, and 8-OHdG was measured by ELISA. The relationships between 8-OHdG levels, stroke subtypes, and clinical outcomes based on the NIHSS and modified Rankin Scale (mRS) upon discharge was evaluated. RESULTS: In the overall cohort, the mean urinary level of 8-OHdG on Day 7 was increased than that on Day 0. The 8-OHdG levels on Day 0 were not different between patients with poor and good outcomes. However, an increasing rate from Day 0 to 7 (Δ 8-OHdG) in stroke patients with a poor outcome(mRS ≥3) was significantly higher than those with a good outcome (mRS ≤2) (2.54 vs 39.44, p = 0.004). CONCLUSIONS: The biochemical changes related to 8-OHdG and oxidative stress may be considered a marker of ischemic brain injury and clinical outcome of ischemic stroke.

Severe insulin allergy successfully treated with continuous subcutaneous insulin infusion.

Insulin allergy is a rare complication of insulin therapy. Proper management, though difficult, is critical. Here, we report the case of a patient with type 2 diabetes and insulin allergy, successfully treated with continuous subcutaneous insulin infusion (CSII).

[A case of clinically mild encephalitis/encephalopathy with a reversible splenial lesion associated with anti-glutamate receptor antibody].

We report the case of an 18-year-old boy who presented with disturbance of consciousness and generalized seizures following flu-like symptoms such as high fever and arthralgia. T2 and diffusion weighted brain magnetic resonance images showed a hyperintense ovoid lesion in the splenium of the corpus callosum and T, weighted images showed a hypointense lesion; the lesion completely disappeared on repeat imaging after 3 days. Antiglutamate epsilon2 receptor antibodies were detected in his cerebrospinal fluid. Although the patient had several episodes of generalized seizures, he completely recovered within 3 months. Our patient had a clinically mild encephalitis/encephalopathy with a reversible splenial lesion following flu-like symptoms, which indicated viral infection. As compared to previously reported cases, our case was characteristic because of the protracted recovery shown by the patient. Anti-glutamate epsilon2 receptor antibodies may be associated with prolonged generalized seizures in the case of our patient. Our results also suggest that anti-glutamate epsilon2 receptor antibodies may play a role in the pathogenesis of this condition.

[Neuromyelitis optica in a patient with Sjögren syndrome with distal renal tubular acidosis: case report].

We report the case of a 31-year-old woman who presented with neuromyelitis optica (NMO) associated with Sjögren syndrome and distal renal tubular acidosis. She was hospitalized because of cervical transverse myelopathy and right optic neuritis. She had been clinically diagnosed with Sj6gren syndrome, with a high titer of anti-SS-A antibody (1:500) and anti-SS-B antibody (1:498). She also showed hypokalemia, metabolic acidosis, and nephrocalcinosis caused by distal renal tubular acidosis associated with Sjögren syndrome. T2-weighted magnetic resonance imaging (MRI) revealed long lesions extending from the medulla oblongata to the lower thoracic cord. In addition, gadolinium-enhanced MRI revealed a right optic nerve lesion in the optic canal. High titer of anti-aquaporin-4 (AQP4) antibody was detected in the patient's serum (1:131,072). A combination therapy comprising steroid pulse therapy and plasmapheresis improved her clinical symptoms, and the administration of oral prednisolone (20 mg/ day) was effective in preventing the recurrence of NMO. In patients with myelitis/transverse myelopathy associated with autoimmune disorders such as Sjögren syndrome, examining the titer values of anti-AQP4 antibody is indispensable in determining the appropriate therapy.

[Case of incomplete brown-Séquard syndrome after thoracic herpes zoster infection].

e report an 87-year-old woman who presented with incomplete Brown-Séquard syndrome after reactivation of varicella-zoster virus (VZV). Two days after herpes zoster in the right side of the chest, she developed weakness of the right lower limb. Neurological examination revealed a spastic palsy in the right lower limb and left side loss of pain and temperature sense to T6. However, vibration and position sense was not impaired in both sides. Spinal T2-weighted MR images showed a high-intensity lesion in the right side of the spinal cord except posL terior funiculus at the level of T2. Cerebrospinal fluid analysis showed 109 leukocytes/mm3, 79 mg/dl protein, negative VZV PCR, elevated titer of anti-VZV IgM and IgG, and increase of IgG index. Although she was treated with a combination of acyclovir and steroid pulse therapy, her weakness in the right lower limb was not improved. In this case, since the posterior funiculus circulated from the posterior spinal artery was not involved, the incomplete Brown-S6quard syndrome may be caused by spinal cord infarction due to VZV vasculitis of the anterior spinal artery.

[A case of retroperitoneal solitary fibrous tumor associated with hypoglycemia].

Solitary fibrous tumor is an uncommon mesenchymal lesion, seldom associated with hypoglycemia and rarely presents as a retroperitoneal tumor. We present a case in a 56-year-old male patient whose initial symptom was unconsciousness due to hypoglycemia (blood glucose 16 mg/dl). Computed tomography indicated a mass (about 20 x 15 x 15 cm) in the retroperitoneum. Only surgical treatment was performed and the patient has been without hypoglycemia and recurrence for 12 months after surgery. This case had "patternless pattern" characterized by a haphazard, storiform arrangement of short spindle or ovoid cells, and "hemangiopericytoma-like appearance" with prominent vascularity by thin-walled vessels, as expressed CD34 immunohistochemically. Pathohistological examination revealed increased cellularity in the tumor tissues as well as tissues with atypical nuclei of the tumor cells with some cell division. Western immunoblotting and immunohistochemistry showed that tumor produced big IGF-II, leading to hypoglycemia. Due to these findings, it was diagnosed as malignant solitary fibrous tumor associated with non-islet cell tumor hypoglycemia (NICTH). This case is the second malignant solitary fibrous tumor in the retroperitoneum with hypoglycemia in the English literature.