Primary care clinic visits in formerly evacuated areas due to radiation disaster following the Great East Japan Earthquake: A retrospective descriptive study.

Radiation disasters pose distinctive medical challenges, requiring diverse care approaches. Beyond radiation exposure assessment, addressing health impacts due to lifestyle changes, especially among vulnerable populations, is vital. Evacuation orders issued in radiation-affected areas introduce unique healthcare dynamics, with their duration significantly influencing the recovery process. Understanding evolving patient demographics and medical needs after lifting evacuation orders is crucial for post-disaster care planning. Minamisoma Municipal Odaka Hospital, located 13 to 20 km from Fukushima Daiichi Nuclear power plant in a post-evacuation zone, was greatly affected by the Great East Japan Earthquake and subsequent radiation disaster. Data were retrospectively collected from patient records, including age, gender, visit date, diagnoses, and addresses. Patient records from April 2014 to March 2020 were analyzed, comparing data before and after the July 2016 evacuation order lift. Data was categorized into pre and post-evacuation order lifting periods, using International Classification of Diseases, Tenth Edition codes, to identify the top diseases. Statistical analyses, including χ-square tests, assessed changes in disease distributions. Population data for Odaka Ward and Minamisoma City fluctuated after lifting evacuation orders. As of March 11, 2011, Odaka Ward had 12,842 residents (27.8% aged 65+ years), dropping to 8406 registered residents and 2732 actual residents by April 30, 2018 (49.7%). Minamisoma City also saw declines, with registered residents decreasing from 71,561 (25.9%) to 61,049 (34.1%). The study analyzed 11,100 patients, mostly older patients (75.1%), between 2014 and 2020. Post-lifting, monthly patient numbers surged from an average of 55.2 to 213.5, with female patients increasing from 33.8% to 51.7%. Disease patterns shifted, with musculoskeletal cases declining from 23.8% to 13.0%, psychiatric disorders increasing from 9.3% to 15.4%, and trauma-related cases decreasing from 14.3% to 3.9%. Hypertension (57.1%) and dyslipidemia (29.2%) prevailed post-lifting. Urgent cases decreased from 1.3% to 0.1%. This study emphasizes the importance of primary care in post-evacuation zones, addressing diverse medical needs, including trauma, noncommunicable diseases, and psychiatric disorders. Changing patient demographics require adaptable healthcare strategies and resource allocation to meet growing demands. Establishing a comprehensive health maintenance system tailored to these areas' unique challenges is crucial for future disaster recovery efforts.

Neurofascin as a target for autoantibodies in peripheral neuropathies.

OBJECTIVES: We asked whether autoantibodies against neurofascin (NF)186 or NF155, both localized at the nodes of Ranvier, are present in serum of patients with inflammatory neuropathy, and whether NF-specific monoclonal antibodies are pathogenic in vivo. METHODS: We cloned human NF155 and NF186, and developed an ELISA and cell-based assay to screen for antibodies to human NF in a total of 434 donors including 294 patients with Guillain-Barré syndrome variants acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal neuropathy, and chronic inflammatory demyelinating polyneuropathy (CIDP). We characterized reactive samples by isotyping, tissue section staining, and epitope mapping. We also injected NF-specific monoclonal antibodies IV into rats with experimental autoimmune neuritis. RESULTS: We detected autoantibodies to NF by ELISA in 4% of patients with AIDP and CIDP, but not in controls. Most positive samples contained immunoglobulin G (IgG)1, IgG3, or IgG4 antibodies directed to only one isoform of NF. Two patients with CIDP showed particularly high (1:10,000 dilution) NF155-specific reactivity in both assays and stained paranodes. Two other patients with CIDP who benefited from plasma exchange exhibited antibodies to NF155 by ELISA, and upon affinity purification, antibodies to both isoforms were observed by both assays. Anti-NF monoclonal antibodies enhanced and prolonged induced neuritis in rats. CONCLUSIONS: Autoantibodies to NF are detected in a very small proportion of patients with AIDP and patients with CIDP, but may nevertheless be pathogenic in these cases.

Nodal proteins are target antigens in Guillain-Barré syndrome.

Neurofascin-186 (NF186), neuronal cell adhesion molecule (NrCAM), and gliomedin are adhesion molecules playing a central role in the formation of nodes of Ranvier. In Guillain-Barré syndrome (GBS), immune attack toward the nodes may participate in the disabilities. Autoantibodies to NF186 and gliomedin have been detected in a rat model of GBS. Here, we investigated the prevalence of antibodies against nodal adhesion molecules in patients with GBS or chronic inflammatory demyelinating polyneuropathy (CIDP). Sera from 100 GBS patients, 50 CIDP patients, 80 disease controls, and 50 healthy controls were tested for their ability to bind the nodes of Ranvier. To characterize the antigens, we performed cell binding assays against NF186, gliomedin, contactin, and NrCAM. We found that 43% of patients with GBS and 30% of patients with CIDP showed IgG fixation at nodes or paranodes. In eight patients with GBS or CIDP, we identified that IgG antibodies recognized the native extracellular domain of NF186, gliomedin, or contactin. Also, 29 patients showed IgM against nodal adhesion molecules. However, we did not detect IgM fixation at nodes or paranodes. Antibodies to gliomedin or NF186 were mostly detected in demyelinating and axonal GBS, respectively. The adsorption of the antibodies to their soluble antigens abolished IgG deposition at nodes and paranodes in nerves, indicating these were specific to NF186, gliomedin, and contactin. In conclusion, gliomedin, NF186, and contactin are novel target antigens in GBS. At nodes, additional epitopes are also the targets of IgG. These results suggest that antibody attack against nodal antigens participates in the etiology of GBS.

Guillain-Barré syndrome associated with normal or exaggerated tendon reflexes.

Areflexia is part one of the clinical criteria required to make a diagnosis of Guillain-Barré syndrome (GBS). The diagnostic criteria were stringently developed to exclude non-GBS cases but there have been reports of patients with GBS following Campylobacter jejuni enteritis with normal and exaggerated deep tendon reflexes (DTRs). The aim of this study is to expand the existing diagnostic criteria to preserved DTRs. From the cohort of patients referred for anti-ganglioside antibody testing from hospitals throughout Japan, 48 GBS patients presented with preserved DTR at admission. Thirty-two patients had normal or exaggerated DTR throughout the course of illness whereas in 16 patients the DTR became absent or diminished during the course of the illness. IgG antibodies against GM1, GM1b, GD1a, or GalNAc-GD1a were frequently present in either group (84 vs. 94%), suggesting a close relationship between the two groups. We then investigated the clinical and laboratory findings of 213 GBS patients from three hospital cohorts. In 23 patients, eight presented with normal tendon reflexes throughout the clinical course of the illness. Twelve showed hyperreflexia, with at least one of the jerks experienced even at nadir, and exaggerated reflexes returning to normal at recovery. The other three had hyperreflexia throughout the disease course. Compared to 190 GBS patients with reduced or absent DTR, the 23 DTR-preserved patients more frequently presented with pure motor limb weakness (87 vs. 47%, p = 0.00026), could walk 5 m independently at the nadir (70 vs. 33%, p = 0.0012), more frequently had antibodies against GM1, GM1b, GD1a, or GalNAc-GD1a (74 vs. 47%, p = 0.014) and were more commonly diagnosed with acute motor axonal neuropathy (65 vs. 34%, p = 0.0075) than with acute inflammatory demyelinating polyneuropathy (13 vs. 43%, p = 0.0011). This study demonstrated that DTRs could be normal or hyperexcitable during the entire clinical course in approximately 10% of GBS patients. This possibility should be added in the diagnostic criteria for GBS to avoid delays in diagnosis and effective treatment to these patients.

Conduction block in acute motor axonal neuropathy.

Guillain-Barré syndrome is divided into two major subtypes, acute inflammatory demyelinating polyneuropathy and acute motor axonal neuropathy. The characteristic electrophysiological features of acute motor axonal neuropathy are reduced amplitude or absence of distal compound muscle action potentials indicating axonal degeneration. In contrast, autopsy study results show early nodal changes in acute motor axonal neuropathy that may produce motor nerve conduction block. Because the presence of conduction block in acute motor axonal neuropathy has yet to be fully recognized, we reviewed how often conduction block occurred and how frequently it either reversed or was followed by axonal degeneration. Based on Ho's criteria, acute motor axonal neuropathy was electrodiagnosed in 18 patients, and repeated motor nerve conduction studies were carried out on their median and ulnar nerves. Forearm segments of these nerves and the across-elbow segments of the ulnar nerve were examined to evaluate conduction block based on the consensus criteria of the American Association of Electrodiagnostic Medicine. Twelve (67%) of the 18 patients with acute motor axonal neuropathy had definite (n=7) or probable (n=5) conduction blocks. Definite conduction block was detected for one patient (6%) in the forearm segments of both nerves and probable conduction block was detected for five patients (28%). Definite conduction block was present across the elbow segment of the ulnar nerve in seven patients (39%) and probable conduction block in two patients (11%). Conduction block was reversible in seven of 12 patients and was followed by axonal degeneration in six. All conduction blocks had disappeared or begun to resolve within three weeks with no electrophysiological evidence of remyelination. One patient showed both reversible conduction block and conduction block followed by axonal degeneration. Clinical features and anti-ganglioside antibody profiles were similar in the patients with (n=12) and without (n=6) conduction block as well as in those with (n=7) and without (n=5) reversible conduction block, indicating that both conditions form a continuum; a pathophysiological spectrum ranging from reversible conduction failure to axonal degeneration, possibly mediated by antibody attack on gangliosides at the axolemma of the nodes of Ranvier, indicating that reversible conduction block and conduction block followed by axonal degeneration and axonal degeneration without conduction block constitute continuous electrophysiological conditions in acute motor axonal neuropathy.

[Case of subdural empyema caused by Porphyromonas and Fusobacterium identified by 16S ribosomal RNA gene sequence analysis].

A 24-year-old woman presented subdural empyema developing from sinusitis caused by Porphyromonas and Fusobacterium infection. She experienced fever and progressive headache with gradually worsening symptoms. Neurological examination revealed drowsiness and neck stiffness. A CSF examination detected pleocytosis and a low glucose level. Gadolinium-enhanced T1-weighted images from brain MRI showed thickening enhancement at the leptomeninges in the left frontal to temporal lobes and interhemispheric fissure with edema. Based on the diagnosis of bacterial meningoencephalitis and subdural empyema developing from sinusitis primary to odontogenic infection, she received antibacterial chemotherapy with meropenem hydrate and vancomycin hydrochloride, after which motor aphasia and consciousness disturbance occurred. No bacteria were isolated from a trans-sphenoidal biopsy specimen and CSF culture. Molecular typing also was performed by sequencing the 16S ribosomal RNA intergenic spacer region, and Porphyromonas and Fusobacterium were identified. She was given cephalosporin and metronidazol, after which her neurological symptoms and signs gradually lessened. Physicians need to be aware that patients may develop subdural empyema subsequent to sinusitis associated with Porphyromonas and Fusobacterium infection and that amplification and sequence analysis of partial bacterial 16S ribosomal RNA gene should be examined when no bacteria is identified by culture.

Anti-GM1 IgG antibodies in Guillain-Barré syndrome: fine specificity is associated with disease severity.

BACKGROUND: Clinical severity of Guillain-Barré syndrome (GBS) is highly variable, but the immunopathological reason is unknown. OBJECTIVE: The study was designed to show which antibody parameters are associated with disease severity in GBS patients with serum anti-GM1 IgG antibodies. METHODS: Thirty-four GBS patients with anti-GM(1) IgG antibodies were grouped into two categories according to disease severity at nadir: mild (grades 1-3 by Hughes functional scale, n=13) and severe (grades 4 and 5, n=21). Titre, affinity, fine specificity and cell binding of anti-GM(1) antibodies were obtained and compared between the two groups. RESULTS: No differences in antibody titre (GM(1)-ELISA) or affinity were found between the two patient groups. In contrast, the severe group showed a significantly higher frequency (95%, vs 46% in the mild group, p=0.002) of specific (not cross-reacting with GD(1b)) anti-GM(1) antibodies. In addition, the severe group also exhibited a higher antibody binding titre to cellular GM(1). CONCLUSIONS: Differences in fine specificity of antibodies are strong indications that different regions of the GM(1)-oligosaccharide are involved in antibody binding. High titres of specific anti-GM(1) antibody binding to cellular GM(1) can be explained by antigen exposure, that is, GM(1) exposes or forms mainly epitopes recognised by specific antibodies, and 'hides' those involved in binding of cross-reacting antibodies. Thus, the fine specificity of anti-GM(1) antibodies may influence disease severity by affecting antibody binding to cellular targets. Additionally, since antibody specificity studies are relatively easy to implement, fine specificity could be considered a useful predictor of disease severity.

BAFF aids generation of IgG anti-ganglioside antibodies in response to Campylobacter jejuni lipo-oligosaccharide.

Ganglioside mimicry of Campylobacter jejuni lipo-oligosaccharide (LOS) can induce the production of IgG anti-ganglioside antibodies, but the generation mechanism has yet to be clarified. B-cell activating factor belonging to the TNF family (BAFF) helped murine B cells produce anti-ganglioside antibodies against C. jejuni LOS. In splenocyte culture, however, anti-ganglioside antibodies were produced in the presence of a soluble transmembrane activator and calcium-modulating and cyclophilin ligand interactor immunoadhesin (TACI-Ig), a receptor for BAFF. TACI-Ig adenoviral vectors failed to decrease production of anti-ganglioside antibodies in mice sensitized with C. jejuni LOS and did not alter IgG subclasses, evidence that BAFF aids but is not essential for the generation of IgG anti-ganglioside antibodies in response to C. jejuni LOS.

[Case of basilar artery occlusion caused by mucormycotic embolism in the course of myelodysplastic syndrome].

We report the case of a man in his sixties with mucormycosis in whom initial cerebellar infarction progressed into pontine infarction due to basilar artery occlusion. He had received blood transfusions for myelodysplastic syndrome for 1 year and suddenly developed ataxic speech and gait disturbances. On the basis of the diagnosis of cerebellar infarction and pneumonia, he was administered antifungal medications (micafungin sodium, fosfluconazole, and amphotericin B) in addition to glycerin, after which the patient suffered from high fever associated with meningeal irritation and consciousness disturbance. Diffusion-weighted images derived from brain magnetic resonance imaging (MRI) revealed the presence of high-signal intensity lesions extending to the bilateral pons. He died of tonsillar herniation associated with brainstem edema. Autopsy revealed mucormycosis occluding and invading the basilar artery, which caused fatal brainstem infarction. This case highlights the importance of the opportunistic infection, namely, mucormycosis, which is caused by Mucor.

[Paraneoplastic cerebellar degeneration and Lambert-Eaton myasthenic syndrome associated with anti P/Q-type voltage-gated calcium channel antibody in a patient with primary double lung cancer].

We report the case of a 50-year-old man with paraneoplastic cerebellar degeneration (PCD) and Lambert-Eaton myasthenic syndrome (LEMS) associated with primary double lung cancer. He developed acute progressive double vision, slurred speech, and gait disturbance. Neurological examination revealed diplopia, mild ptosis, bilateral horizontal gaze-evoked nystagmus, and cerebellar limb and truncal ataxia. The diffusion image of brain magnetic resonance imaging (MRI) revealed no abnormal findings in the cerebellum. On the basis of the diagnosis of acute cerebelitis, he was given methylprednisolone pulse therapy followed by oral prednisolone, which gradually improved his neurological signs and symptoms. The analysis of the possible etiology suggested that the PCD was induced by lung cancer, which led to ataxia. A chest computed tomography scan revealed mass lesions of irregular shape and unclear margins in the upper lobe of the right lung and a small nodule tumor in the upper lobe of the left lung. We performed transbronchial needle aspiration and detected the bronchioloalveolar carcinoma of the right lung. An electromyogram showed waxing phenomenon in the ulnar nerve at high-frequency (50Hz) stimulation. The serum levels of anti-P/Q-type voltage-gated calcium channel (VGCC) antibody were elavated in the patient. These findings confirmed that the pathogenesis of the condition of this patient to be associated with LEMS. His cerebellar symptoms were considered to be caused by the PCD, and the diplopia, ptosis, and hyporeflexia were attributed to LEMS. We performed upper left lobectomy with mediastinal lymphnode dissection via video-assisted thoracoscopic surgery. A histological study detected small cell carcinoma. A diagnosis of double primary lung cancer was made. Physicians need to be aware that patients may develop PCD and LEMS associated with anti-VGCC antibody caused by small cell lung cancer, and a mass survey should be conducted and careful examinations performed.

[Case of Leber's hereditary optic neuropathy with mitochondrial DNA 11778 mutation exhibiting cerebellar ataxia, dilated cardiomyopathy and peripheral neuropathy].

We report the case of a 28-year-old woman with Leber's hereditary optic neuropathy (LHON) associated with cerebellar ataxia, dilated cardiomyopathy and peripheral neuropathy. She had a mitochondrial DNA point mutation from guanine to adenine at nucleotide position 11778 and developed ataxic gait within 2 years after the onset of bilateral visual loss. A neurological examination detected horizontal nystagmus, bradylalia, and truncal and bilateral limb ataxia of the cerebellar type. She could walk, albeit unsteadily. There was no weakness in her arms and legs. Tendon jerks were diminished in both the upper arms. Bilateral knee and ankle jerks were absent, and the plantar responses were neutral. Paresthesia of the stocking type was present but no reduction of pinprick, position or vibration senses was detected in the paresthetic regions. Romberg's sign was negative. Brain MRI showed atrophic changes in both the cerebellar vermis and the hemispheres. Nerve conduction studies detected mildly decreased motor nerve conduction velocities in the median, ulnar and posterior tibial nerves. Ultrasound cardiography showed a dilated left ventricle. It was not possible to clarify the relationship between LHON and cerebellar atrophy, cardiomyopathy, and peripheral neuropathy. However, physicians, need to be aware that the patients may develop various neurological complications after the onset of optic neuropathy in LHON.

[Pontine hemorrhage in a patient with type 1 renal tubular acidosis associated with osmotic demyelination syndrome].

Here, we report the case of a 23-year-old man with type 1 renal tubular acidosis (RTA) associated with osmotic demyelination syndrome (ODS) who developed pontine hemorrhage. Acute progressive tetraparesis had developed during the clinical course of the RTA. Neurological examination revealed bilateral weakness in all 4 limbs associated with severe hypokalemia (K 1.4 mEq/L). He experienced a sudden onset of general convulsions and mutism during the treatment for metabolic acidosis and hypokalemia. The T2-weighted MR image of the brain revealed multiple hyperintense signal lesions in the central pons as well as in the extrapontine sites of the bilateral cortical and subcortical areas in the frontal and parietal lobes. A T2-star (T2*)-weighted MR image showed focal hemorrhagic lesions in the lower pons. On the basis of the diagnosis of ODS, he underwent corticosteroid and thyrotropin-releasing hormone therapy, after which his neurological signs and symptoms have gradually reduced. While analyzing the possible etiology, it has been suggested that osmotic vascular injuries induced by elevated levels of serum potassium and osmolarity give rise to edema and vascular endothelial damage; these conditions, consequently lead to hemorrhagic necrosis. Physicians need to be aware that RTA patients may develop ODS after hypokalemia, and the potassium levels need to be corrected carefully. (Received: November 6, 2007, Accepted: June 11, 2008)

[CSF filtration and interferon-beta for Guillain-Barré syndrome].

Cerebrospinal fluid (CSF) filtration has been proposed as a new treatment for Guillain-Barré syndrome (GBS). The theory behind filtering the CSF is that soluble pathogenetic factors or inflammatory mediators including cytokines might be removed from a site where nerve conduction could be impeded or nerve root damage inflicted. There is no pathologic background to recommend continuing with CSF filtration in GBS. Interferon is an immunoregulatory cytokine that reduces relapse frequency in multiple sclerosis and ameliorates experimental autoimmune neuritis, an animal model of GBS. A trial showed that interferon beta-1a would be safe in patients with GBS, but the sample size was too small to detect anything other than a large effect.

[Case of diabetes mellitus associated with cervical pyogenic spondylitis and meningoencephalitis secondary to retropharyngeal abscess caused by Streptococcus pneumoniae].

A 63-year-old man with diabetes mellitus had undergone insulin therapy for 10 years. He developed symptoms of upper respiratory tract infection and neck pain. After 5 days, he suddenly experienced high fever and consciousness disturbance. Neurological examination detected drowsiness and neck stiffness. Cerebrospinal fluid (CSF) examination revealed pleocytosis with low glucose level. Gram staining and a latex agglutination test of his CSF revealed Streptococcus pneumoniae to be the causative organism of meningoencephalitis in the patient. Gadolinium-enhanced T1-weighted images obtained from a cervical spine MRI showed ring enhancement in the anterior clivus and thickening in the anterior dura matter with specific thickening at the dens of the axis. Based on the diagnosis of cervical pyogenic spondylitis and meningoencephalitis secondary to retropharyngeal abscess caused by Streptococcus pneumoniae, the patient was administered panipenem/betamipron and dexamethasone, following which his neurological symptoms and signs gradually improved. Diabetes mellitus is a factor that predisposes patients to invasive pneumococcal infection. Thus, we conclude that physicians need to be aware of the possible development of cervical pyogenic spondylitis and meningoencephalitis subsequent to Streptococcus pneumoniae infection, and symptoms such as fever and neck pain should be carefully examined.