Volume 138, Issue 1, January 2015

This scientific commentary refers to ‘Treatment-induced neuropathy of diabetes: an acute, iatrogenic complication of diabetes’ by Gibbons and Freeman (10.1093/brain/awu307).

This scientific commentary refers to ‘Temporal lobe surgery in childhood and neuroanatomical predictors of long-term declarative memory outcome’ by Skirrow et al. (10.1093/brain/awu313).

This scientific commentary refers to ‘Human N-methyl D-aspartate receptor antibodies alter memory and behaviour in mice’ by Planagumà et al. (doi: 10.1093/brain/awu310).

This scientific commentary refers to ‘Neutralization of TNFSF10 ameliorates functional outcome in a murine model of Alzheimer’s disease’ by Cantarella et al. (doi: 10.1093/brain/awu318).

Visual impairment is a key manifestation of multiple sclerosis, and correlates with reduced quality of life. Balcer et al. review current knowledge of vision and visual outcomes in multiple sclerosis, and provide recommendations for the management of visual impairment, the conduct of clinical trials, and topics for future research.

Adenosine’s analgesic effects have previously been attributed to A₁ and A_2A adenosine receptors. However, Little et al. now show that A₃ adenosine receptor activation by endogenous adenosine and potent agonists selectively suppresses persistent pain states by activating brain-to-spinal cord circuits that inhibit pain processing. Targeting A₃ receptors could help relieve chronic pain.

Harston et al. establish proof of principle for clinical use of pH-weighted MRI in patients with acute ischaemic stroke. Detailed tissue-level analysis reveals that cerebral intracellular pH, a marker of metabolic stress, is associated with eventual tissue outcome, and complements established imaging modalities.

Treatment induced neuropathy of diabetes is an iatrogenic neuropathy that develops in the setting of a rapid improvement in glycaemic control. Through retrospective review of case records, Gibbons and Freeman reveal that symptom severity and the risk of developing the disorder correlate strongly with the magnitude of glycaemic change.

See Low and Singer (10.1093/brain/awu327) for a scientific commentary on this article.

Microglia have been implicated in amyotrophic lateral sclerosis (ALS) progression, but the underlying mechanisms are unclear. Mesci et al. reveal that suppression of system $xC−$ (a cystine/glutamate transporter) reduces microglia-triggered glutamate excitotoxicity and switches microglia to a neuroprotective phenotype: this slows disease progression and increases neuronal survival in ALS mice.

Senatorov et al. reveal a bilateral reduction in anterior insula volume, and bilateral increase in amygdala volume, in alcohol-dependent subjects compared to healthy controls. Post-mortem histological studies suggest that the lower anterior insula volumes may reflect a 60% reduction in von Economo neurons in subjects with a history of alcoholism.

See Berg (doi:10.1093/brain/awu320) for a scientific commentary on this article.

In a long-term follow-up study of children who underwent temporal lobe surgery for treatment of epilepsy, Skirrow et al. identify no significant pre-to-post-surgery memory losses, but instead robust improvements in memory functions supported by the unoperated temporal lobe. The integrity of remaining temporal lobe structures places constraints on long-term memory outcomes.

Planagumà et al. show that infusing CSF from patients with anti-NMDAR encephalitis into the mouse brain induces progressive memory and behavioural deficits that correlate with levels of brain-bound human NMDAR-antibodies and a reduction in NMDARs. The changes, which are reversible, confirm the pathogenicity of NMDAR-antibodies and have therapeutic implications.

See Honnorat (doi:10.1093/brain/awu342) for a scientific commentary on this article.

Giannetti et al. use the PET ligand [11C]-(R)-PK11195 to explore microglial activation in normal-appearing white matter of subjects with clinically isolated syndrome. Microglial activation is increased in patients compared to healthy controls, and increased in subjects who develop multiple sclerosis within two years compared to those who do not.

Wegener et al. reveal that upregulation of Olig2 in oligodendrocyte progenitor cells enhances their migration and differentiation, leading to precocious myelination in prenatal mice and accelerated remyelination of lesions in adults. The presence of Olig2 in regenerating oligodendrocytes in multiple sclerosis lesions suggests that its upregulation could facilitate myelin repair.

Post-stroke fatigue is common, but its causes are unclear. Using TMS to investigate motor functioning in affected individuals, Kuppuswamy et al. show that low levels of excitability of the cortical areas that control motor output are associated with high levels of post-stroke fatigue.

In a double-blind sham-controlled study in stroke patients, Lefebvre et al. show that transcranial direct current stimulation improves learning and one-week retention of a motor skill performed with a paretic upper limb. They also reveal a trend towards normalisation of brain activation patterns during execution of the learned motor skill.

Little is known about how non-V1 inputs influence motion area V5/MT+. Ajina et al. reveal that after V1 damage, V5/MT+ activity resembles that of early visual cortex, perhaps driven by similar subcortical inputs. While these inputs are normally overshadowed by V1 connections, acknowledging their contribution may improve neuronal models.

Cerebral amyloid angiopathy is an important risk factor for cognitive impairment. Reijmer et al. use multimodal MRI and amyloid PET imaging to report changes in the brain network structure, which may represent a key step between small vessel brain disease and cognitive and gait impairment.

Auditory spatial processing is vulnerable in dementia. Golden et al. show that patients with typical Alzheimer’s disease or posterior cortical atrophy are impaired relative to controls in detecting the movement and location of sounds. The deficits have anatomical correlates in right parietal cortex, with implications for studies of network degeneration.

See Frenkel (doi:10.1093/brain/awu334) for a scientific commentary on this article.

TNFSF10, a pro-apoptotic cytokine of the TNF superfamily, is released during amyloid-related neurodegeneration. Cantarella et al. show that neutralization of TNFSF10 reduces cognitive deficits in the triple transgenic mouse model of Alzheimer’s disease. Hippocampal amyloid-beta, gliosis and inflammation are also reduced, suggesting that TNFSF10 has potential as a therapeutic target.

A single dose of heroin can reduce stress responses in heroin-dependent patients. Schmidt et al. report that increased amygdala-related functional connectivity during fearful face processing in heroin-dependent patients transiently normalises after a single dose of heroin. This measure may help to assess the efficacy of maintenance treatments in drug addiction.