[123I]Iomazenil SPECT Detects a Reversible Lesion of the Left Medial Temporal Lobe in a Case of Global Autobiographical Amnesia.

Global autobiographical amnesia is a rare disorder that is characterized by a sudden loss of autobiographical memories covering many years of an individual's life. Generally, routine neuroimaging studies such as CT and MRI yield negative findings in individuals with global autobiographical amnesia. However, in recent case reports, functional analyses such as SPECT and fMRI have revealed changes in activity in various areas of the brain when compared with controls. Studies using iomazenil (IMZ) SPECT with individuals with global autobiographical amnesia have not been reported. We report the case of a 62-year-old Japanese woman with global autobiographical amnesia who had disappeared for ∼4 weeks. [123I]-IMZ SPECT showed reduced IMZ uptake in her left medial temporal lobe and no significant reduction on N-isopropyl-[123I] p-iodoamphetamine (IMP) SPECT in the identical region. Because IMZ binds to the central benzodiazepine receptor, this dissociation between IMZ and IMP SPECT was thought to reflect the breakdown of inhibitory neurotransmission in the left medial temporal lobe. Moreover, when the woman recovered most of her memory 32 months after fugue onset, the IMZ SPECT-positive lesion had decreased in size. Because the woman had long suffered verbal abuse from her former husband's sister and brother, which can also cause global autobiographical amnesia, it is difficult to conclude whether the IMZ SPECT-positive lesion in the left medial temporal lobe was the cause or the result of her global autobiographical amnesia. Although only one case, these observations suggest that IMZ SPECT may be useful in uncovering the mechanisms underlying global autobiographical amnesia.

Prevalence of elevated serum anti-N-methyl-D-aspartate receptor antibody titers in patients presenting exclusively with psychiatric symptoms: a comparative follow-up study.

BACKGROUND: Increasing numbers of patients with elevated anti-N-methyl-D-aspartate (NMDA) receptor antibody titers presenting exclusively with psychiatric symptoms have been reported. The aim of the present study was to clarify the prevalence of elevated serum anti-NMDA receptor antibody titers in patients with new-onset or acute exacerbations of psychiatric symptoms. In addition, the present study aimed to investigate the association between elevated anti-NMDA receptor titers and psychiatric symptoms. METHODS: The present collaborative study included 59 inpatients (23 male, 36 female) presenting with new-onset or exacerbations of schizophrenia-like symptoms at involved institutions from June 2012 to March 2014. Patient information was collected using questionnaires. Anti-NMDA receptor antibody titers were measured using NMDAR NR1 and NR2B co-transfected human embryonic kidney (HEK) 293 cells as an antigen (cell-based assay). Statistical analyses were performed for each questionnaire item. RESULTS: The mean age of participants was 42.0 ± 13.7 years. Six cases had elevated serum anti-NMDA antibody titers (10.2 %), four cases were first onset, and two cases with disease duration >10 years presented with third and fifth recurrences. No statistically significant difference in vital signs or major symptoms was observed between antibody-positive and antibody-negative groups. However, a trend toward an increased frequency of schizophrenia-like symptoms was observed in the antibody-positive group. CONCLUSION: Serum anti-NMDA receptor antibody titers may be associated with psychiatric conditions. However, an association with specific psychiatric symptoms was not observed in the present study. Further studies are required to validate the utility of serum anti-NMDA receptor antibody titer measurements at the time of symptom onset.

Resection of Gastric Cancer Remitted Anti-signal Recognition Particle Myopathy.

A 72-year-old woman presented with gradually-worsening myalgia and muscle weakness of the proximal lower limbs as well as elevated serum creatine kinase level. Based on a clinicoseropathological examination including a muscle biopsy, she was diagnosed with anti-signal recognition particle (SRP) myopathy. Although the myopathy relapsed two times in two years under oral prednisolone and intravenous immunoglobulin therapy, the myopathy remained in remission for more than three years after resection of gastric cancer. Although the anti-SRP myopathy is not considered to be cancer-associated in general, we should note that some cases of anti-SRP myopathy may be ameliorated with appropriate cancer treatment.

A Patient with Noonan Syndrome with a KRAS Mutation Who Presented Severe Nerve Root Hypertrophy.

We report a 45-year-old female with clinical features resembling Noonan syndrome (NS) who presented with significant nerve root hypertrophy. She was initially diagnosed with Charcot-Marie-Tooth disease because her gait disturbance gradually deteriorated and nerve conduction velocity was reduced. However, she did not carry a PMP22 gene mutation. RASopathies are a group of phenotypically overlapping developmental syndromes caused by germline mutations that encode components of the Ras/MAPK signaling pathway. These disorders include NS, cardiofaciocutaneous (CFC) syndrome, and Costello syndrome and are associated with molecular abnormalities in the Ras/MAPK pathway. The patient was suspected to have NS and related disorders because of pulmonary artery stenosis, lymphedema, distinctive facial appearance, and intellectual disability. Genetic analysis identified a heterozygous de novo mutation in KRAS (c.211T>G, p.Tyr71Asp), which is usually observed in patients with NS or CFC syndrome. Although our patient was diagnosed with NS, she revealed clinical manifestations that were typical to CFC syndrome, including intellectual disability. It has been reported that some patients diagnosed with RASopathies with mutations in PTPN11, SOS1, or KRAS developed nerve root hypertrophy. These results suggest that nerve root hypertrophy may be associated with RASopathy, although the onset mechanisms of nerve root hypertrophy are unknown.

Cybernic treatment with wearable cyborg Hybrid Assistive Limb (HAL) improves ambulatory function in patients with slowly progressive rare neuromuscular diseases: a multicentre, randomised, controlled crossover trial for efficacy and safety (NCY-3001).

BACKGROUND: Rare neuromuscular diseases such as spinal muscular atrophy, spinal bulbar muscular atrophy, muscular dystrophy, Charcot-Marie-Tooth disease, distal myopathy, sporadic inclusion body myositis, congenital myopathy, and amyotrophic lateral sclerosis lead to incurable amyotrophy and consequent loss of ambulation. Thus far, no therapeutic approaches have been successful in recovering the ambulatory ability. Thus, the aim of this trial was to evaluate the efficacy and safety of cybernic treatment with a wearable cyborg Hybrid Assistive Limb (HAL, Lower Limb Type) in improving the ambulatory function in those patients. RESULTS: We conducted an open-label, randomised, controlled crossover trial to test HAL at nine hospitals between March 6, 2013 and August 8, 2014. Eligible patients were older than 18 years and had a diagnosis of neuromuscular disease as specified above. They were unable to walk for 10 m independently and had neither respiratory failure nor rapid deterioration in gait. The primary endpoint was the distance passed during a two-minute walk test (2MWT). The secondary endpoints were walking speed, cadence, and step length during the 10-m walk test (10MWT), muscle strength by manual muscle testing (MMT), and a series of functional measures. Adverse events and failures/problems/errors with HAL were also evaluated. Thirty patients were randomly assigned to groups A or B, with each group of 15 receiving both treatments in a crossover design. The efficacy of a 40-min walking program performed nine times was compared between HAL plus a hoist and a hoist only. The final analysis included 13 and 11 patients in groups A and B, respectively. Cybernic treatment with HAL resulted in a 10.066% significantly improved distance in 2MWT (95% confidence interval, 0.667-19.464; p = 0.0369) compared with the hoist only treatment. Among the secondary endpoints, the total scores of MMT and cadence at 10MWT were the only ones that showed significant improvement. The only adverse effects were slight to mild myalgia, back pain, and contact skin troubles, which were easily remedied. CONCLUSIONS: HAL is a new treatment device for walking exercise, proven to be more effective than the conventional method in patients with incurable neuromuscular diseases. TRIAL REGISTRATION: JMACTR, JMA-IIA00156.

[Incomplete Gerstmann syndrome with a cerebral infarct in the left middle frontal gyrus].

A 65-year-old right-handed man noted a sudden onset of numbness and weakness of the right hand. On the initial visit to our hospital, he showed severe acalculia, and transient agraphia (so called incomplete Gerstmann syndrome) and transcortical sensory aphasia. Brain MRI revealed a fresh infarct in the left middle frontal gyrus. The paragraphia and aphasia improved within 14 days after onset, but the acalculia persisted even at seven months after onset In an 123I-IMP SPECT study, the cerebral blood flow (CBF) was found to be decreased in the infarction lesion and its adjacent wide area, the ipsilateral angular and supramarginal gyri, and contralateral cerebellar hemisphere. We speculate that inactivation in the infarction lesion caused the CBF decrease in the non-infarcted areas due to diaschisis. This case indicates that Gerstmann syndrome can be caused by not only dysfunction of the angular gyrus but also of the left middle frontal gyrus in the dominant hemisphere.

Neurosarcoidosis Occurring 6 Years after Onset of Vogt-Koyanagi-Harada Disease.

A 43-year-old Japanese woman visited a clinic with a 2-week history of visual loss, hyperemia, and bilateral eye pain. Dilated fundus and optical coherence tomography showed hyperemic optic disc and multifocal serous retinal detachments. Fundus fluorescein angiography revealed optic disc leakage and numerous hyperfluorescent pinpoints of leakage, which are typical of Vogt-Koyanagi-Harada disease (VKHD). She also showed tinnitus, poliosis, and alopecia. With a diagnosis of VKHD, steroid therapy was started. At the age of 48, oral prednisolone was tapered off, and only corticosteroid eye drops were continued. Eighteen months later, dysesthesia appeared in the left side of her face and in her left ring and little fingers, which spread to the ulnar side of her forearm. Blood tests indicated elevated serum angiotensin-converting enzyme (ACE) levels. Chest CT showed bilateral lymphadenopathy, and histological analysis of the subcutaneous mass in her right arm showed multinucleated giant cells. Steroid therapy was started under a diagnosis of sarcoidosis. Serum ACE and lysozyme levels decreased in response to steroid therapy. We report a case of the concurrence of VKHD and sarcoidosis, which may share a common pathophysiology. Accumulation of further similar cases is necessary to elucidate the precise mechanism underlying the concurrence of these two diseases.

Significance of N-isopropyl-[123I] p-iodoamphetamine single-photon emission computed tomography in detection of responsible hypoperfusion in hemichorea.

Hemichorea is relatively an uncommon clinical presentation while its known etiology are vascular, metabolic, neoplastic, infectious, autoimmune, and inherited disorders. In the acquired case of hemichorea, the most common cause is the cerebrovascular insult, which is often diagnosed by the magnetic resonance (MR) imaging. An 84-year-old woman reported a one-week history of involuntary movements in the left side of her face and left limbs. Blood tests were normal and brain MR imaging showed no responsible hyperintense lesion on T1-, FLAIR, and diffusion-weighted imaging. N-isopropyl-[123I] p-iodoamphetamine single-photon emission computed tomography (SPECT) detected hypoperfusion in the right thalamus. Further three-dimensional tomography clearly detected the hypoperfusion in the right subthalamic nucleus. The hypoperfused lesion was MR-negative and remained unchanged in SPECT one year after the onset. After the treatment with 0.35 mg of oral haloperidol was initiated, the hemichorea was gradually decreased and completely disappeared in 9 months. Because the three-dimensional analysis performs voxel-by-voxel analysis, it possibly detects the precise hypoperfusion in a specific region. In conclusion, evaluation of cerebral blood flow using SPECT on patients presenting with acute hemichorea can lead to the detection of responsible lesion when the routine examinations are negative.

Postural Abnormality in Parkinson's Disease: A Large Comparative Study With General Population.

BACKGROUND: Postural abnormalities in Parkinson's disease (PD) patients and unimpaired elderly are not well differentiated. Factors related to postural abnormality associated with PD are controversial. OBJECTIVE: We assessed differences in postural change between PD patients and unimpaired elderly and elucidated factors related to abnormal posture in PD patients. METHODS: We measured the dropped head angle (DHA), anterior flexion angle (AFA), and lateral flexion angle (LFA) of the thoracolumbar spine of an unprecedented 1,117 PD patients and 2,732 general population participants (GPPs) using digital photographs. Two statistical analyses were used for elucidating factors related to these angles. RESULTS: In GPPs, age was correlated with DHA, AFA, and LFA. DHAs, AFAs, and LFAs of PD patients and age-matched GPPs were 21.70° ± 14.40° and 13.13° ± 10.79°, 5.98° ± 12.67,°and - 3.82° ± 4.04°, and 0.86° ± 4.25° and 1.33° ± 2.16°, respectively. In PD patients, factors related to DHA were age, male sex, and H & Y stage during ON time. Factors related to AFA were age, duration of disease, H & Y stage during ON and OFF times, pain, vertebral disease, and bending to the right. A factor related to LFA was AFA. CONCLUSIONS: DHA and AFA of GGPs correlated with age and were larger in PD patients than those with in GPPs. Some PD patients showed angles far beyond the normal distribution. Thus, factors associated with disease aggravation affected postural abnormality in PD patients.

Reversible limbic encephalitis with antibodies against the membranes of neurones of the hippocampus.

The authors report a patient with limbic encephalitis associated with an ovarian teratoma. An antibody against the membranes of neurones of the hippocampus was identified in both serum and CSF. Immunosuppressive treatments such as plasmapheresis and high-dose intravenous immunoglobulin administration resulted in a rapid clinical recovery.