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01.12.2011 | Case report | Ausgabe 1/2011 Open Access

Journal of Medical Case Reports 1/2011

Severe brain atrophy after long-term survival seen in siblings with familial amyotrophic lateral sclerosis and a mutation in the optineurin gene: a case series

Journal of Medical Case Reports > Ausgabe 1/2011
Hiroki Ueno, Keitaro Kobatake, Masayasu Matsumoto, Hiroyuki Morino, Hirofumi Maruyama, Hideshi Kawakami
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1752-1947-5-573) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Authors' contributions

HU compiled the data and interpreted the CT studies. KK analyzed and interpreted the patient data regarding the neurological disease. HMa, HMo and HK diagnosed the OPTN mutation. MM, HM, HM and HK helped conceive the study and design and helped co-ordinate the study. HU was a major contributor in writing the manuscript. All authors read and approved the final manuscript.



Previous studies have shown widespread multisystem degeneration in patients with sporadic amyotrophic lateral sclerosis who develop a total locked-in state and survive under mechanical ventilation for a prolonged period of time. However, the disease progressions reported in these studies were several years after disease onset. There have been no reports of long-term follow-up with brain imaging of patients with familial amyotrophic lateral sclerosis at an advanced stage of the disease. We report the cases of siblings with amyotrophic lateral sclerosis with homozygous deletions of the exon 5 mutation of the gene encoding optineurin, in whom brain computed tomography scans were followed up for more than 20 years.

Case presentation

The patients were a Japanese brother and sister. The elder sister was 33 years of age at the onset of disease, which began with muscle weakness of her left lower limb. Two years later she required mechanical ventilation. She became bedridden at the age of 34, and died at the age of 57. A computed tomography scan of her brain at the age of 36 revealed no abnormality. Atrophy of her brain gradually progressed. Ten years after the onset of mechanical ventilation, atrophy of her whole brain, including the cerebral cortex, brain stem and cerebellum, markedly progressed. Her younger brother was 36 years of age at the onset of disease, which presented as muscle weakness of his left upper limb. One year later, he showed dysphagia and dysarthria, and tracheostomy ventilation was performed. He became bedridden at the age of 37 and died at the age of 55. There were no abnormal intracranial findings on brain computed tomography scans obtained at the age of 37 years. At the age of 48 years, computed tomography scans showed marked brain atrophy with ventricular dilatation. Subsequently, atrophy of the whole brain rapidly progressed as in his elder sister.


We conclude that a homozygous deletion-type mutation in the optineurin gene may be associated with widespread multisystem degeneration in amyotrophic lateral sclerosis.

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