Long-term neurological and neuropsychological complications of sulfur mustard and Lewisite mixture poisoning in Chinese victims exposed to chemical warfare agents abandoned at the end of WWII.

In August 2003, 44 victims were poisoned by chemical warfare agents (CWAs) leaked from five drums that were excavated at a construction site in Qiqihar, Northeast China. The drums were abandoned by the former Japanese imperial army during World War II and contained a mixture of Sulfur mustard (SM) and Lewisite. We carried out a total of six regular check-ups between 2006 and 2014, and from 2008 we added neurological evaluations including neuropsychological test and autonomic nervous function test in parallel with medical follow-up as much as was possible. Severe autonomic failure, such as hyperhidrosis, pollakiuria, diarrhoea, diminished libido, and asthenia appeared in almost all victims. Polyneuropathy occurred in 35% of the victims and constricted vision occurred in 20% of them. The rates of abnormal response on cold pressor test (CPT), active standing test (AST), Heart rate variability (CVR-R), performed in 2014, were 63.1%, 31.6%, and 15.9%, respectively. On neuropsychological testing evaluated in 2010, a generalized cognitive decline was observed in 42% of the victims. Memories and visuospatial abilities were affected in the remaining victims. Finally, a 17-item PTSD questionnaire and the Beck Depression Inventory evaluated in 2014 revealed long-lasting severe PTSD symptoms and depression of the victims. Our findings suggest that an SM/Lewisite compound have significant adverse consequences directly in cognitive and emotional network and autonomic nervous systems in the brain.

Coiled-coil domain containing 85B suppresses the beta-catenin activity in a p53-dependent manner.

Aberrant accumulation of beta-catenin is closely related to carcinogenesis. Mutations in the p53 gene are reported to induce the aberrant accumulation of beta-catenin in the absence of dysfunction in the glycogen synthase kinase 3beta (GSK3beta)-mediated degradation pathway, but the mechanism remains incompletely understood. Here, we show that human coiled-coil domain containing 85B (CCDC85B) is induced by p53 and regulates beta-catenin activity via interaction with the T-cell factor 4 in the nucleus. Moreover, CCDC85B enhances the degradation of beta-catenin and suppresses tumor cell growth. In conclusion, we revealed that CCDC85B-induced degradation of beta-catenin is independent of GSK3beta and other p53-inducible products, Siah-1L, suggesting that CCDC85B constitutes the one of the frameworks of p53-induced multiple regulatory pathways for beta-catenin activity.

Prosopagnosia: a clinical and anatomical study of four patients.

We tested in great detail face perception and face memory in four cases of prosopagnosia. Three of them showed deficits of face perception and/or of familiar faces memory. There was one prosopagnosic patient, however, who showed no abnormality in face perception and discrimination and could recall familiar faces. This case suggests that a form of prosopagnosia may exist, which is due to the disconnection between face perception and face memory. X-ray CT, MRI and PET studies revealed that two patients did not have damage of the left hemisphere, supporting the view that prosopagnosia can arise from unilateral right-sided lesion.

[Hypoglycemic encephalopathy demonstrating generalized multiple cortical infarctions--sequential CT findings].

A fifty-nine-year-old alcoholic man with severe hypoglycemic encephalopathy was examined using sequential CT scans of the brain (CT). Twenty-seven hours after the attack, which resulted in a comatose state, CT disclosed multiple low density areas throughout the cerebral cortex which resembled multiple cortical infarctions. CT obtained four days after the ictus demonstrated more prominent low density areas in the cerebral cortex, diffuse cerebral edema and partial cortical enhancement after administration of contrast medium. Sixteen days after the ictus, the multiple low density areas in the cerebral cortex disappeared. Enhanced CT on day 23 demonstrated marked gyral enhancement throughout the cerebral cortex. Thereafter diffuse brain atrophy progressed rapidly as demonstrated by MRI on day 82 which showed extensive cortical and subcortical atrophy particularly in the frontoparietal and parieto-occipital regions bilaterally with dilated lateral ventricles. Hypoglycemia and anoxia have long been thought to give rise to similar types of brain damage based on neuropathological observations. But it has recently been shown that they are quite different based on neurochemical and neurophysiological findings. Numerous previously reported autopsy cases of hypoglycemia confirm these findings which are neuropathologically similar to the multiple infarction seen in the present case. We conclude that the acute cortical changes of the present case are specific for hypoglycemic encephalopathy. The findings indicate that the basic mechanisms operating in hypoglycemia and anoxia are different.

Cheiro-oral topography of sensory disturbances due to lesions of thalamocortical projections.

Sensory disturbance in the unilateral hand and ipsilateral mouth region, the cheiro-oral syndrome, may be due to cortical, thalamic, or brainstem lesions. We report five patients with this syndrome due to infarction at the border of the posterior limb of the internal capsule and the corona radiata. The sensory fibers from the mouth area and hand probably travel to the cortical sensory areas in close proximity after leaving the posterior ventral thalamic nucleus.

[A case of acute mountain sickness with bilateral lesion of pallidum].

The patient was 56-year-old female, who suffered from ataxia and then fell into coma on the next day after she had moved from the sea level to an altitude of 4,200 m. After she was brought to lower altitude, consciousness recovered within several hours. For about 2 days thereafter, disorientation was observed, and she was diagnosed as AMS (acute mountain sickness). Only insomnia continued in chronic stage. The results of X-ray computed tomography (CT) on 25th day after the onset of the disease revealed no abnormal finding except the slightly increasing uptake of contrast material. Symmetrical low density regions were seen in bilateral basal ganglia after one year, and the globus pallidus lesions were confirmed by magnetic resonance imaging. In the past, cerebral edema has been reported in most cases of AMS, and the neurotic symptoms of AMS have been attributed to cerebral edema, while the essential condition of this disease is not yet elucidated. In the present case, the globus pallidus lesions could be identified through the following-up of the central nervous system by X-ray CT and MRI as the first attempt for the case of AMS. There has been no report of globus pallidus lesions in the cases of AMS. Whereas low oxygen partial pressure is the primary cause of AMS, and it is highly probable that the disorders in globus pallidus as reported in the cases of carbon monoxide poisoning, anesthetic accident, etc. are related to the occurrence of AMS.

[Paroxysmal cerebellar ataxia--an evaluation using the findings from magnetic resonance imaging, positron emission tomography, and acetazolamide treatment].

Paroxysmal cerebellar ataxia (PCA) is a specific disease which exhibits spasmodic cerebellar ataxia but rarely shows abnormal neurological findings in the intermission. Verger first described an isolated case. Subsequent reports of the disease included mostly cases with autosomal dominant inheritance, but the reports have been limited to about 20 families. Although both the lesion and the cause have not been clearly identified, since Vighetto et al. demonstrated the atrophy of the anterosuperior region of the cerebellar vermis using magnetic resonance imaging (MRI), the lesion of PCA captured the attention of researchers. The patient was a 40-year-old male, who exhibited spasmodic inarticulation and dizziness during walking when he was 10 years old. The symptoms gradually became aggravated in both frequency and duration. Abnormal findings were observed by electroencephalography and Hydantol F was given with no successful effect. The results of a CT scan of the head revealed no abnormality, whereas those of MRI revealed the atrophy in the folia of anterosuperior region of the cerebellar vermis by MRI as in the case of Vighetto et al., and PCA was suspected. Findings from positron emission tomography (PET) for the first time disclosed the abnormality in the cerebellar vermis and brainstem, and suggested an organic disorder in the cerebellar vermis and a functional abnormality in the cerebellum and brainstem. Since the report by Griggs et al., it has been known that acetazolamide is effective for PCA although the pharmacological mechanism is not yet clear. In our present case, the attack was improved in both frequency and duration by the administration of acetazolamide, and the effectiveness of acetazolamide in the patient was confirmed.(ABSTRACT TRUNCATED AT 250 WORDS)

[Reading and writing deficit in cases of localized infarction of the left anterior thalamus].

We have observed two cases with marked reading and writing deficits, in which speech and oral comprehension were generally intact. Detailed symptomatological study was performed on these cases, and the lesions were examined organically (X-ray computed tomography [X-ray CT], magnetic resonance imaging [MRI] and functionally (positron emission tomography [PET]. In addition to the marked reading and writing deficits, mild naming and memory disorders were found. X-ray CT and MRI revealed that the lesions were limited to the regions fed by the polar and paramedian arteries in the left thalamus. In one case, PET demonstrated a functional disturbance of the left parietal and temporal lobes in addition to the left thalamus. Most previous cases have shown lesions in the anterior portion of the thalamus. It is possible that the reading and writing deficits in these cases may be due to the thalamic lesion itself, but the PET findings strongly suggest that a secondary cortical lesion may be involved in producing the higher cognitive disorders.

[Antemortem diagnosis of Marchiafava-Bignami disease].

Marchiafava-Bignami disease (M-B disease) is a peculiar disease, observed in hardened drinkers and resulting in demyelinization and necrosis of the corpus callosum. The clinical symptoms are diverse, and it is difficult to diagnose accurately while the patient is alive. Almost all reports in the past have been based on necropsy. Only three cases of M-B disease have been reported in Japan so far, none of which was based on a diagnosis while the patient was alive. We have been able to perform diagnosis of M-B disease while the patients were still alive by means of X-ray computed tomography (CT) and magnetic resonance imaging (MRI), and to study the clinical symptoms from the acute stage. In addition to the study on our own patients, we also conducted a neurosymptomatic study on the clinical symptoms of 6 cases, for which details of the symptomatology have been described-out of about 150 cases reported in the past. In the acute stage of M-B disease, we observed psychic symptoms, such as clouding of consciousness, mnemonic disorders and disorders and disorientation, or various frontal lobe symptoms, such as change in personality, raptus nervorum, dysphemia, pyramidal signs and astasia-abasia. These are non-specific symptoms and it is necessary to differentiate from encephalitis and other encephalopathy. In the chronic stage, dysphemia becomes sustained and, in addition, symptoms of transection of the corpus callosum are noted among the disorders of higher cerebral functions. If M-B disease is suggested from clinical symptoms, it is advisable to confirm the lesions in the corpus callosum by X-ray CT and MRI.(ABSTRACT TRUNCATED AT 250 WORDS)

[Alexia with agraphia produced by localized infarction in the inferior posterior region of the left temporal lobe].

There have been several reports on alexia with agraphia due to hemorrhage or trauma in the inferior posterior region of the left temporal lobe since Yamadori (1982) first reported a case of cerebral hemorrhage. We presented the first case of alexia with agraphia due to a circumscribed infarct in the inferior posterior region of the left temporal lobe. A 65-year-old right-handed man had an acute onset of inability to read Japanese "kana" letters and to write any letters. He had no difficulty in speaking or understanding. Neurological examination on admission was normal except for homonymous quadrantanopia in the right upper field. Neuropsychological findings: Spontaneous speech was fluent without dysprosody. There were no disturbances in auditory understanding or in repetition. He could read Japanese "kanji" characters correctly, however, he could not read any "kana" letters. Writing was also disturbed severely even as to his address, name or telephone number. Calculation was also difficult. There were no disturbances in naming colors, no ideomotor or constructional apraxia nor visual agnosia. X-ray computed tomography (CT) scan showed a faint low density area with ring enhancement suggesting a cerebral infarct in the inferior posterior region of the left temporal lobe. Patient's hospital course was characterized by a marked improvement of alexia, especially of "kana" letters as compared with that of "kanji" characters. Dissociative improvement of alexia compared with agraphia in this case could be explained by the fact that the lesion was in close contact with the occipital lobe and that he also had pure alexia in the early stage.