SCA27 caused by a chromosome translocation: further delineation of the phenotype.

We report of a spinocerebellar ataxia (SCA)27 in a daughter and her mother whose karyotype is 46, XX t(5;13)(q31.2;q33.1). The translocation breakpoint is identical in both patients, disrupting the gene-encoding fibroblast growth factor 14 isoform b (FGF14-1b). Clinically, both show signs of SCA, although the daughter is the most affected with early onset cerebellar ataxia, microcephaly, and severe mental retardation. FGF14-1b is the predominant isoform in brain, where it interacts with the voltage gated Na channel. Fgf14(-/-) mice develop ataxia and paroxysmal dyskinesia and have cognitive deficits. One missense and one non-sense mutation in FGF14 have previously been linked to SCA27. Truncation of one allele in our patients suggests that haploinsuffiency of FGF14 can cause SCA27.

Hazardous peak concentrations of hydrogen sulfide gas related to the sewage purification process.

The concentration of hydrogen sulfide in the atmosphere of a sewage purification plant in Norway was studied. Continuous measurements over several 3-week periods showed that the concentrations generally were lower than 2 ppm, but peak concentrations over 100 ppm were discovered. Rapid onset and decline characterized these peak concentrations, which occurred at regular intervals. Through evaluation of the time pattern of these peaks compared with plant operations, a specific process was identified as the likely causative factor of the spikes. Through simple remedial actions the hydrogen sulfide concentration associated with this activity was reduced from above 100 ppm to less than 2 ppm. Olfactory fatigue to hydrogen sulfide and strong offensive odors from other compounds in the sewage makes smell ineffective for signaling high concentrations. Peak concentrations may therefore pass unnoticed unless detected with continuous measuring equipment. The risk for exposure may be reduced by enclosing processes and through the use of spot extraction ventilation in areas with compacted anaerobic waste material.

[Chronic CO poisoning. Use of generator gas during the second world war and recent research]. / Kronisk CO-forgiftning. Bruken av generatorgass under den annen verdenskrig og nyere forskning.

The consequences of long-lasting and low-grade exposure to carbon monoxide are a matter of debate. During the second world war, lack of petrol led to widespread use of wood as fuel (generator gas vehicles), especially in the Nordic countries. This caused many cases of "acute" or "chronic" carbon monoxide poisoning. Typical symptoms of "chronic poisoning" were headache, dizziness and tiredness. Usually the symptoms disappeared after some weeks or month, but in some patients probably became permanent. The experiences from the generator gas era are now almost forgotten, and chronic carbon monoxide poisoning is easily overlooked. The authors describe two cases of such poisoning. A crane driver at a smelting works developed permanent symptoms after twenty years of exposure. A faulty oil-fired central heating system caused long-lasting symptoms in four members of a family.

[Hypoxic brain damage after carbon monoxide poisoning. Visual agnosia, reduced initiative and memory and delayed sequelae]. / Hypoksiske hjerneskader etter forgiftning med karbonmonoksid. Visuell agnosi, nedsatt initiativ og hukommelse og forsinkede skader.

Four patients with hypoxic brain damage caused by carbon monoxide poisoning are described. Three of these had attempted suicide with car exhaust fumes. Two patients had visual agnosia due to lesions in the parieto-occipital cortex. Three patients had temporary Parkinsonian symptoms. In two of these patients CT and MRI showed lesions in the globus pallidus. They also showed reduced initiative, and in one patient this was combined with minor tics and obsessive symptoms. One patient had impaired memory as the only symptom. The patient with the longest lasting exposure developed delayed sequelae; three weeks after the poisoning he became apathetic and confused, with failing memory, Parkinsonian symptoms, and urinary and faecal incontinence. MRI showed demyelination in the periventricular white matter. His condition started to improve two months after the accident.

[Delayed symptoms of hypoxic brain damage after temporary improvement]. / Forsinkede symptomer på hypoksisk hjerneskade etter forbigående bedring.

A shipyard worker was doing welding work inside a pipe with argon as cover gas. After taking a break he fainted while controlling the weld, also inside the pipe. He was rescued after 15-20 minutes and regained consciousness after a few hours. Two days later he was discharged from hospital in apparently good health. After a week he returned to the hospital suffering from confusion, failing memory, aphasia, apraxia and urinary incontinence. MR showed elevated signal intensity bilaterally in the caudate nucleus. He improved gradually and six months later was given less demanding work. The course of his illness is consistent with delayed neuropsychiatric sequelae after hypoxia, probably due to displacement of oxygen by argon. Delayed symptoms are caused by demyelination in the subcortical white matter.

Regional cerebral blood flow after long-term exposure to carbon disulfide.

Sixteen former rayon viscose workers were investigated four years after the exposure to carbon disulfide was discontinued. Median age was 58 years (range 43-65 years), median exposure time was 17 years (range 10-35 years). Encephalopathy was diagnosed in altogether 14 workers. To further explore pathophysiological mechanisms, cerebrovascular investigations were employed. Doppler ultrasound examination of the precerebral vessels in 15 workers showed a slight stenosis of the left internal carotid artery in one. Regional cerebral blood flow investigation (rCBF) with single photon emission computerized tomography (SPECT) with Xenon-133 gas was performed in 14. There was no significant difference from a control group. Regional side-to-side asymmetries beyond reference limits were demonstrated in eight workers. The abnormalities were modest, but may indicate a tendency toward focal blood flow disturbances in workers with long-term exposure to carbon disulfide.

Delayed neuropsychiatric sequelae after acute hydrogen sulfide poisoning: affection of motor function, memory, vision and hearing.

A shipyard worker was poisoned by hydrogen sulfide (H2S), and rescued after 15-20 min. He regained consciousness after 2 days. Three days later his condition deteriorated, and he was more or less comatose for a month. When he woke up, he was amnesic, nearly blind, had reduced hearing, and had a moderate spastic tetraparesis and ataxia. Two months after the accident, he had greatly improved. Audiograms showed hearing loss with maximum at 2000 Hz and significantly poorer speech discrimination. EEG showed generalized dysrhythmia. At follow-up 5 years later he had not been able to resume his work, and had slight motor, memory and visual symptoms. CT and MRI showed slight cerebral atrophy. EEG and evoked responses were normal.

Brain damage caused by hydrogen sulfide: a follow-up study of six patients.

Hydrogen sulfide (H2S) poisoning involves a risk of hypoxic brain damage. Six patients who lost consciousness due to H2S poisoning are described. The symptoms varied from anosmia in the patient with the shortest but highest exposure to delayed neurological deterioration in the patient with the longest exposure. The two patients with the most serious symptoms developed pulmonary edema, which may have prolonged the hypoxia. The patients were reexaminated 5 years or more after the poisoning. The five patients who had been unconscious in H2S atmosphere for from 5 to 15-20 min showed persisting impairment at neurological and neuropsychological re-examination. Memory and motor function were most affected. One patient was seriously demented. Recent reports of large groups of H2S-poisoned workers probably underestimate the risk of sequelae, due to the inclusion of cases with exposure of short duration and lack of follow-up.

Carbon disulfide exposure and neurotoxic sequelae among viscose rayon workers.

In Norway's only viscose rayon plant, carbon disulfide (CS2) concentrations in ambient air usually were between 30 and 50 mg/m3 during the first 23 years of production. From 1970/1971 until the factory was closed in 1982, corresponding values were 10-25 mg/m3. Through all of these years, high peak exposures of CS2 and H2S occurred. In 1986, 16 of the 24 men still at work in 1982 and with at least 10 years' experience in the spinning room agreed to participate in this study. Clinical neurological examination demonstrated abnormalities in 15; neuropsychological tests showed impairments of probable organic origin in 14. Thirteen had cerebral atrophy demonstrated by cerebral computed tomography (CT). Electromyography (EMG) was abnormal in six, neurography in 11. Regional cerebral blood flow measurements indicated flow asymmetries in eight, whereas Doppler investigation of the extracranial carotid and vertebral arteries, electroencephalography (EEG), and evoked response investigations were mostly normal. Based on these results and the exposure data, a diagnosis of CS2-induced encephalopathy was reached in eight workers; another six had an encephalopathy in which CS2 exposure was regarded as a partial cause. Correspondingly, seven had a neuropathy probably caused by CS2 exposure alone; in three others, CS2 was found to be the partial cause of a neuropathy. This indicates that long-term, relatively moderate exposure to CS2 in association with high peak exposures to CS2 and H2S involves a substantial risk of developing neurotoxic disease.

[H2S poisoning and nervous system damage]. / H2S-forgiftning og skader i nervesystemet.

H2S (hydrogen sulfide) is a very toxic gas. Even brief exposure to high concentrations may be fatal. Unconsciousness may occur without warning. Those who try to help are often poisoned too. In Norway, most poisonings have been described in connection with the herring oil and fish meal industry, farmers handling manure, and sewage work. The risk of hypoxic damage to the nervous system is considerable. The clinical picture varies, and the connection between the patients' symptoms and the poisoning is easily overlooked, especially with delayed sequelae, which may occur several weeks after the acute poisoning. The risk of damage depends on both the exposure time and the concentration of H2S, and a thorough anamnesis, noting the course of events, is important in order to achieve a correct diagnosis.

[Late sequelae after occupational exposure to organic solvents. Exposure assessment in diagnosing chronic toxic encephalopathy]. / Senskader etter yrkeseksponering for organiske løsemidler. Vurdering av eksponeringen i den diagnostiske utredning av kronisk toksisk encefalopati.

Organic solvents are debated as a cause of chronic toxic encephalopathy. The pathogenesis is not completely known. There are some indications of structural changes in the central nervous system. Epidemiological studies are saddled with potential faults and methodological problems, but in total the epidemiological evidence for a causal association between solvents and encephalopathy is sound. The first step in the diagnosis is to demonstrate encephalopathy by neurological and neuropsychological methods. The next step is to estimate the probability of solvents being the cause of this encephalopathy. Misjudgement of diagnosis is often due to uncertainty in the exposure evaluation. We discuss elements of the exposure assessment, and outline neuropsychological testing as part of the diagnostic process.

Chronic toxic encephalopathy among house painters with disability pension.

Among a group of 14 painters accorded a disability pension, 11 showed signs and symptoms of slight encephalopathy. Five of these 11 painters previously had been pensioned with a diagnosis of musculoskeletal disease, while the encephalopathy was unrecorded in the disability pension records. The combined effect of the two diseases may have caused the disability. We considered occupational solvent exposure the most probable cause of the encephalopathy in four of these five painters. This study indicates that case-referent studies based on diagnoses from disability pension registers may lead to underestimation of the risk of toxic encephalopathy.

[Nervous system damage caused by H2S poisoning without unconsciousness]. / Skade av nervesystemet etter H2S-forgiftning uten bevisstløshet.

Acute H2S (hydrogen sulfide) poisoning can cause permanent damage to the nervous system. We describe two patients with such damage. Both reported nausea, feeling unwell and irritation of the eyes during work, and have developed persistent memory problems and neurasthenic symptoms. Neither of them had been unconscious. The first patient was exposed during one and a half hours welding of a sewage pump. The second patient worked for three weeks in a laboratory where hydrogen sulfide leaked from faulty equipment. The cases demonstrate the need for thorough work and symptom anamnesis together with neuropsychological testing in order to achieve a correct diagnosis of encephalopathy caused by hydrogen sulfide exposure.

Neurological examination, computerized tomography, cerebral blood flow and neuropsychological examination in workers with long-term exposure to carbon disulfide.

Sixteen males, formerly exposed to carbon disulfide (CS2) for at least 10 years (mean 20 years), were administered a neurological examination, cerebral computerized tomography (CT), regional cerebral blood flow (rCBF) examination and neuropsychological examination. The clinical neurological examination revealed abnormalities in 15; cerebral CT showed signs of atrophy in 13; and neuropsychological examination indicated brain organic changes in 13. With the rCBF examination, slight abnormalities were found in 8. The findings indicate that long-term exposure to CS2 involves a risk of developing toxic encephalopathy, demonstrable on both neurological and neuropsychological examination. Furthermore, structural changes in the brain may be demonstrable by cerebral CT.