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Objective: Since the first report of CHCHD10 gene mutations in amyotrophiclateral sclerosis (ALS)/frontotemporaldementia (FTD) patients, genetic variation in CHCHD10 has been inconsistently linked to disease. A pathological assessment of the CHCHD10 protein in patient neuronal tissue also remains to be reported. We sought to characterise the genetic and pathological contribution of CHCHD10 to ALS/FTD in Australia., Methods: Whole-exome and whole-genome sequencing data from 81 familial and 635 sporadic ALS, and 108 sporadic FTD cases, were assessed for genetic variation in CHCHD10 . CHCHD10 protein expression was characterised by immunohistochemistry, immunofluorescence and western blotting in control, ALS and/or FTD postmortem tissues and further in a transgenic mouse model of TAR DNA-binding protein 43 (TDP-43) pathology., Results: No causal, novel or disease-associated variants in CHCHD10 were identified in Australian ALS and/or FTD patients. In human brain and spinal cord tissues, CHCHD10 was specifically expressed in neurons. A significant decrease in CHCHD10 protein level was observed in ALS patient spinal cord and FTD patient frontal cortex. In a TDP-43 mouse model with a regulatable nuclear localisation signal (rNLS TDP-43 mouse), CHCHD10 protein levels were unaltered at disease onset and early in disease, but were significantly decreased in cortex in mid-stage disease., Conclusions: Genetic variation in CHCHD10 is not a common cause of ALS/FTD in Australia. However, we showed that in humans, CHCHD10 may play a neuron-specific role and a loss of CHCHD10 function may be linked to ALS and/or FTD. Our data from the rNLS TDP-43 transgenic mice suggest that a decrease in CHCHD10 levels is a late event in aberrant TDP-43-induced ALS/FTD pathogenesis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Neurofibromatosis type 1 (NF1) is a multisystem disease associated with a lifelong risk of debilitating and potentially life-limiting complications, however many adults with NF1 have no regular health surveillance. We interviewed and examined 17 young adults with NF1 between the ages of 25 and 33. Most had not been assessed for NF1-related complications within the previous 8 years, including patients with known serious vascular complications, for example, renal artery stenosis. Acute and/or chronic pain, particularly back and plexiform-related pain were common symptoms, and despite a significant impact on quality of life, was untreated in most instances. Symptom and examination-directed imaging revealed serious complications in 41% of the cohort. These included severe spinal cord compression (two cases), a highly SUV avid lesion suggestive of malignancy (one case), and a Juvenile Pilocytic Astrocytoma in a patient without any previous NF1-related complications. Few study participants had a good understanding of NF1, its associated risks and complications, and many had not sought appropriate medical advice as questions or problems arose. NF1-related cognitive deficits in some participants, and the lack of a clear source of expert medical advice for adults with NF1 likely contributed to poor health surveillance and management in this population. Overall, these findings suggest that many Australian adults with NF1 are at risk of serious and life-threatening medical complications, but are not accessing and receiving adequate health care. Access to multidisciplinary adult clinics that specialize in NF1 may address many of the unmet health needs of young adults with NF1., (Copyright © 2013 Wiley Periodicals, Inc.)

Objectives: To characterise West Australian cases of longitudinally extensive myelopathy (LEM)., Methods: Twenty six patients with LEM were identified from a cohort of 983 patients with demyelinating disease. Clinical and MRI data and AQP4-IgG results were reviewed., Results: LEM cases were classified as conventional MS (CMS) 13, neuromyelitis optica (NMO) 7, and isolated LEM 6. LEM was the initial presentation in 13/26 cases. In CMS cases lesions were mainly in the lower cervical cord (C4-C7) whereas in NMO and isolated LEM they were more often thoracic and were longer. The severity of disability was highly variable but was greater in the NMO than the CMS group. Only one of 20 patients tested was seropositive for AQP4-IgG., Conclusion: LEM occurred as part of CMS or NMO or in isolation. Patients with LEM had highly heterogeneous clinical characteristics and a low rate of AQP4-IgG seropositivity.

The incidence of injuries to the spinal cord sustained at rugby in South Africa, New Zealand and Australia is reviewed. Ninety-seven injuries seen at Stoke Mandeville Hospital at the National Spinal Injuries Centre (NSIC) between 1956 and 1993 are analysed in detail. There were 93 accidents at rugby union, two at American football and two at rugby league. The injuries were of the cervical spine apart from four hysterics and one thoracic injury. The thoracic injury occurred after the game when the player fell downstairs. The injuries were analysed according to the mechanism of injury, the neurological condition, the causation, the standard of the player and the position in the field. The injuries caused were the result of force being applied to the skull which was transmitted to the cervical spine resulting in injury to the cervical cord. As a result of this research, representations were made to the appropriate authorities and changes in the laws were made. As a result of these law changes there has been a dramatic reduction in the overall number of injuries and the elimination of the injury from the loose scrum. This paper discusses the historical sequence of how these preventative measures came about to reduce the incidence of injuries and the legal implications whereby the authors took part in two law suits. The legal consequences are analysed in detail.

The mercury levels in 69 muscle samples from fish weighing from 0.3 to 200 kg caught in Moreton Bay, Queensland, in the latter half of 1976 ranged from less than 10 to 2,030 ng/g. Mercury levels in blood samples from 53 humans and 100 dogs in Brisbane almost all contained less than 10 ng/ml while the level in 162 cats sampled ranged from less than 10 to 329 ng/ml. Chronic methylmercurialism developed in 2 cats dosed daily with methylmercury, bound to cysteine, at the rate of 0.6 mg/kg body weight for 74 and 77 days respectively. Terminal clinical signs included anorexia, weight loss, knuckling over at the carpus and tarsus, hypermetria initially involving the forelegs and later the hindlegs, sluggish reflexes, paresis involving all limbs, persistent crying, apparent blindness, tonic and clonic convulsions and salivation. Pathological changes were confined to the nervous system and included degeneration of neurones and perivascular cuffing in the cerebrocortical grey matter, focal atrophy of the granular layer, focal spongiosus of the molecular layer and degeneration and loss of Purkinje cells in the cerebellum and demyelination in the fibre tracts of the dorsal funiculus, mainly the fasciculus cuneatus and in the lateral and ventral corticospinal tracts. Terminal blood methylmercury levels were in excess of 18 microgram/ml, while brain methylmercury levels ranged from 21.0 to 28.4 microgram/g. The liver and kidney contained the highest total levels of mercury of 50 to 80 microgram/g, of which 23 to 37% was inorganic.

Among 20 consecutive autopsies of amyotrophic lateral sclerosis (ALS) occurring in Caucasians in Western Australia (WA), 85% were males. The median age of onset was 58.9 years and the average duration of illness was 2.4 years. Twenty-two randomly selected ALS occurring among natives in Guam also showed a male predominance of 75%, younger age of onset (median 48.5 years) and longer survival period (median 3.4 years). 45% of the WA patients presented with bulbar involvement at the time of first examination. These patients had the lowest median survival period of 1.5 years when compared with the other forms of ALS, the classic upper and lower motor system involvement and progressive muscular atrophy. Theneuropathologic lesions of ALS in WA and Guam were similar with the exception that neurofibrillary tangles were frequently present in the Guamanian brains. In 14%, neuronal loss, gliosis and frequency of tangles in the cerebral cortex especially in Ammon's horn, substantia nigra, and locus ceruleus, were sufficiently severe to indicate the coexistence of another disorder, Parkinsonism-Dementia Complex. This condition was not clinically recognized. In the WA cases only one patient had tangles in the brain and he had concurrent Alzheimers disease. While senile plaques were present in this patient they were usually absent in the Guamanian brains.

Humpy back, a disease of Merino sheep in western Queesland, occurs during mustering for shearing. It is usually seen in summer 6-10 weeks after substantial rainfall and is thought to be caused by the ingestion of a toxic plant. The disease is characterised clinically by a short-stepping, stilted gait of the hind limbs, followed by lowering of the head, arching of the back and inability to continue walking. Histopathological examination of 8 cases from 5 properties revealed a Wallerian degeneration of the white matter throughout the length of the spinal cord with the ventral and lateral columns most severely affected. A similar degenerative change was seen in the posterior cerebellar peduncles of 3 of the sheep. A more severe hind limb incoordination with more extensive degeneration of the white matter of the spinal cord, medulla and cerebellum was seen in a case of humpy back of two years duration. Similar, but much milder, spinal cord lesions were found in apparently unaffected sheep from the same group as the sheep affected with humpy back on 2 properties. Severe myodegeneration of hind limb muscle groups was seen in 3 affected sheep. It was thought to be associated with the long rail journey (1500 km) to the laboratory after the sheep were affected in the field.