The application of shotgun metagenomics to the diagnosis of granulomatous amoebic encephalitis due to Balamuthia mandrillaris: a case report.

BACKGROUND: Granulomatous amoebic encephalitis (GAE) is an infrequent and fatal infectious disease worldwide. Antemortem diagnosis in this condition is very difficult because clinical manifestations and neuroimaging are nonspecific. CASE PRESENTATION: A 60-year-old Japanese woman was admitted with a chief complaint of left homonymous hemianopsia. Brain-MRI showed extensive necrotizing lesions enhanced by gadolinium, in the right frontal lobe, right occipital lobe, and left parietal lobe. Epithelioid granulomas of unknown etiology were found in the biopsied brain specimens. Shotgun metagenomic sequencing using a next-generation sequencer detected DNA fragments of Balamuthia mandrillaris in the tissue specimens. The diagnosis of granulomatous amoebic encephalitis was confirmed using an amoeba-specific polymerase chain reaction and immunostaining on the biopsied tissues. CONCLUSIONS: Shotgun metagenomics is useful for the diagnosis of central nervous system infections such as GAE wherein the pathogens are difficult to identify.

Appearance of bitemporal periodic EEG activity in the last stage of Gerstmann-Sträussler-Scheinker syndrome (Pro102Leu): A case report.

EEG findings in advanced Gerstmann-Sträussler-Scheinker syndrome (GSS) are shown. A 56-year-old woman developed GSS symptoms and was diagnosed as having GSS with the P102L mutation at age 58. During the early stage, there were no significant EEG findings. Her clinical condition worsened and she developed akinetic mutism at age 62. The patient died of pneumonia at age 65. EEGs were recorded annually from age 61 to 65. Bilateral independent periodic discharges (BIPDs) in both temporal areas appeared at age 64. No clinical seizures were noticed. MEG showed the sharp waves of BIPDs originated independently in each temporal lobe. Other causes of BIPDs were absent.

Enlarged, multifocal upper limb neuropathy with HTLV-I associated myelopathy in a patient with chronic adult T-cell leukemia.

The authors herein describe a case of multifocal peripheral neuropathy with HTLV-I-associated myelopathy (HAM) in a patient with chronic adult T-cell leukemia (ATL). The clinical features included subacute progressive sensory-motor neuropathy in the bilateral upper limbs, and bilateral pyramidal tract involvement with bladder dysfunction. An MRI with (67)gadolinium enhancement revealed enlargement of the affected peripheral nerves. (8)FDG positron emission tomography (PET) disclosed increased uptake in the affected nerves, suggesting neurolymphomatosis or inflammation. Anti-HTLV-I antibody was positive in both the serum and CSF. The HTLV-I proviral load in the peripheral blood mononuclear cells was high. Chemotherapy for ATL resulted in marked improvement of motor functions in the upper limbs. This is the first case of multifocal upper limb neuropathy with HAM in a patient with chronic ATL.

Guillain-Barré syndrome and optic neuritis after Mycoplasma pneumoniae infection.

We report the case of a 12-year-old girl who developed Guillain-Barré syndrome (GBS) and optic neuritis (ON) following Mycoplasma pneumoniae infection. Her symptoms, including bilateral vision impairment and tingling in her hands and right foot, were resolved after methylprednisolone pulse therapy. Serum anti-galactocerebroside (Gal-C) IgM antibodies were detected in our patient. This is the first report of a child with GBS and ON associated with M. pneumoniae infection.

Correlation between clinical and radiologic features of patients with Gerstmann-Sträussler-Scheinker syndrome (Pro102Leu).

BACKGROUND AND PURPOSE: Gerstmann-Sträussler-Scheinker syndrome is a rare hereditary neurodegenerative disorder with clinical heterogeneity. This study is aim to demonstrate the clinical spectrum and radiologic characteristics of patients caused by Pro102Leu mutation in PRNP. MATERIALS AND METHODS: We retrospect clinical manifestations of five patients from four Japanese families, and comprehensively analyzed their brain MRI, SPECT (N-isopropyl-p-[123I] iodoamphetamine), and PET (18F-2-fluoro-2-deoxy-d-glucose) images. RESULTS: All patients developed ataxia of lower limbs and trunk, gait disturbance, dysesthesia in legs, and lower limb hyporeflexia. In the early clinical stage before dementia began, no noticeable abnormalities could be observed from brain MRI, but SPECT and PET revealed mosaic-like pattern of blood flow and glucose metabolism of the brain. Predominant abnormalities were found in the occipital and frontal lobes on SPECT and PET analysis, respectively. In SPECT analysis, blood flow of the anterior cerebellar lobes was lower than that of the posterior cerebellar lobes. CONCLUSIONS: Clinical symptoms resulting from failure of dorsal horn of spinal cord and spinocerebellar tracts were observed in all cases. Radiologic findings revealed individual differences of involved region in their brain, which could produce clinical diversity. We identified a downtrend of blood flow in the anterior cerebellar lobes, a projection field of the spinocerebellar tracts, which is an important feature of Gerstmann-Sträussler-Scheinker syndrome.

Toxocara canis myelitis involving the lumbosacral region: a case report.

CONTEXT: Toxocara canis is a parasite known to cause visceral larva migrans. The infection rarely affects the central nervous system but there have been several reports of myelitis caused by visceral larva migrans due to Toxocara canis. In previous reported cases, the lesions were located in the thoracic or cervical spinal cord. To the best of our knowledge, this is the first report of a lesion involving the lumbosacral region. FINDINGS: A 60-year-old man developed weakness and dysesthesia in the lower limbs. The symptoms resolved spontaneously, but recurred after five months. One month later, the patient developed pollakiuria and constipation. He was a dog owner and frequently ate raw chicken meat and beef liver. Sagittal T2-weighted image (T2WI) showed swelling and hyperintensity in the spinal cord from T10 to the lumbosacral region and focal nodular enhancement on the posterior segment of the lumbar spinal cord. Blood cell counts showed slight eosinophilia and elevated serum immunoglobulin E level. Cerebrospinal fluid examination showed slight pleocytosis with eosinophilia. Enzyme-linked immunosorbent assay showed high levels of anti-Toxocara antibodies in the serum and cerebrospinal fluid. In addition, confirmatory test by Western blot was positive. The patient was initially treated with intravenous methylprednisolone with slight improvement in muscle weakness. Albendazole was added with a second course of intravenous methylprednisolone. The muscle weakness in the lower limbs improved considerably, and swelling and hyperintensity on T2WI almost disappeared. CONCLUSION: Our results suggest that Toxocara canis myelitis cannot be discounted even if the myelitis involves the lumbosacral region.

New type of encephalomyelitis responsive to trimethoprim/sulfamethoxazole treatment in Japan.

OBJECTIVE: To determine the causative pathogen and investigate the effective treatment of a new type of encephalomyelitis with an unknown pathogen in Japan and report the preliminary ultrastructural and genomic characterization of the causative agent. METHODS: From 2005 to 2012, we treated 4 Japanese patients with geographic clustering and comparable clinical features, serum/CSF cytology, and radiologic findings. Brain biopsy was conducted in all patients to analyze neuropathologic changes by histology, and electron microscopy was applied to reveal the features of the putative pathogen. Genomic DNA was obtained from the affected brain tissues and CSF, and an unbiased high-throughput sequencing approach was used to screen for specific genomic sequences indicative of the pathogen origin. RESULTS: All patients exhibited progressive dementia with involuntary tongue movements. Cytologic examination of CSF revealed elevated mononuclear cells. Abnormal MRI signals were observed in temporal lobes, subcortical white matter, and spinal cord. Biopsied brain tissue exhibited aggregated periodic acid-Schiff-positive macrophages and 2-7 µm diameter round/oval bodies without nuclei or cell walls scattered around the vessels. Unbiased high-throughput sequencing identified more than 100 archaea-specific DNA fragments. All patients were responsive to trimethoprim/sulfamethoxazole (TMP-SMX) plus corticosteroid therapy. CONCLUSIONS: We report 4 cases of encephalomyelitis due to an unknown pathogen. On the basis of ultrastructural and genomic studies, we propose a new disease entity resulting from a causative pathogen having archaeal features. TMP-SMX therapy was effective against this new type of encephalomyelitis.

[The electrophysiologic diagnosis for muscle ion channelopathies].

The periodic paralysis (PP) and myotonic syndromes have been recognized as muscle ion channelopathies (MIC) consequent to the discovery of genetic abnormalities of muscle ion channels. Genetic studies are therefore indispensable in the diagnosis of MIC. However, it is not practical to examine all muscle ion channels immediately upon identification of clinical symptoms. Clinical symptoms of MIC occur due to the abnormal excitability of the muscle membrane which is in turn related to abnormal ion channel genes. Therefore, a series of electrophysiologic tests is useful in examining the characteristics of abnormal excitability and predicting the abnormal ion channel Needle EMG studies can detect myotonic discharges while the prolonged exercise test can distinguish between primary and secondary PP. For myotonia, pattern I which includes the repeated short exercise test at room temperature or at cold skin temperature is specific for paramyotonia congenita, pattern II is characteristic for myotonia congenita, and pattern III is useful for Na channel myotonia. The decrement of CMAP with 10 Hz repetitive stimulation is related to mutation type in myotonia congenita. Thus, these electrophysiological tests may be of use in screening for MIC to narrow down the diagnosis and the selection of candidates for gene analysis.