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Issue Cover
Volume 140, Issue 2
February 2017
ISSN 0006-8950
EISSN 1460-2156

Editorial

Scientific Commentaries

This scientific commentary refers to ‘Predicting neurosurgical outcomes in focal epilepsy patients using computational modelling’, by Sinha et al. (doi:10.1093/brain/aww299).

This scientific commentary refers to ‘Genetic inactivation of glutamate neurons in the rat sublaterodorsal tegmental nucleus recapitulates REM sleep behaviour disorder’, by Valencia Garcia et al. (doi:10.1093/brain/aww310).

This scientific commentary refers to ‘Trajectories of prediagnostic functioning in Parkinson disease’, by Darweesh et al. (doi:10.1093/brain/aww291).

This scientific commentary refers to ‘Finding the imposter: brain connectivity of lesions causing delusional misidentifications’, by Darby et al. (doi:10.1093/brain/aww288).

Tags: delusions, brain

Review Article

In tauopathies and synucleinopathies, the normally soluble intracellular proteins tau and alpha-synuclein become insoluble and filamentous. Goedert et al. review recent evidence for non-cell autonomous mechanisms of aggregate formation in these disorders. Increasing data suggest that nucleation-dependent aggregation occurs in a localised fashion, and is followed by seed-dependent propagation.

Report

Koch et al. report biallelic mutations in CAD, encoding an enzyme of pyrimidine biosynthesis, in four children with developmental disability, epileptic encephalopathy, anaemia and anisopoikilocytosis. Two died following progressive neurodegeneration; the surviving children showed a striking clinical response to uridine. The findings establish CAD deficiency as a treatable neurometabolic disorder.

Original Articles

Hereditary spastic paraplegias are heterogeneous neurodegenerative disorders characterized by progressive lower limb spasticity. Estrada-Cuzcano et al. report that mutations in the lysosomal transport ATPase gene ATP13A2 – previously associated with Kufor-Rakeb syndrome – cause HSP, and present the first data implicating impaired autophosphorylation of ATP13A2 in the pathogenesis of ATP13A2-associated disease.

Epilepsy is common in Rett syndrome, but seizure burden over time is unclear. By following 778 affected individuals for 3939 person-years, Tarquinio et al. show that the lifetime risk of epilepsy is almost 90%, but that most patients experience remission. The results will contribute to the planning of therapeutic trials.

See Eissa and Schevon (doi:10.1093/aww332) for a scientific commentary on this article.

Neurosurgical treatment of focal epilepsy is highly unpredictable in cases where a lesion is not apparent by any imaging modality. Sinha et al. propose a computational approach to predict the outcome of a planned resection prior to surgery and investigate the pathophysiology of epileptic networks to delineate cortical areas crucial for ictogenesis.

Traumatic brain injury (TBI) can lead to the neurodegenerative disease chronic traumatic encephalopathy (CTE). Using a computational TBI model, Ghajari et al. show that mechanical strain during head injury is greatest in sulci — the principal sites of CTE pathology — paving the way for improvements to areas such as helmet design.

Spontaneous intracranial hypotension (SIH) is usually treated with an epidural blood patch (EBP), but response rates vary and there are no clear outcome predictors. Wu et al. identify specific brain and spinal imaging measures which, together with EBP blood volume, can be used to predict targeted first-EBP response in SIH.

Neuroinflammation is thought to contribute to the failure to recover functions lost to stroke. Stokowska et al. show that C3a-C3aR signalling stimulates neural plasticity in a mouse model of ischaemic stroke. Intranasal treatment with C3a increases synaptic density and axonal plasticity, and leads to faster and more complete functional recovery.

Falik-Zaccai et al. report a novel human progressive leukoencephalopathy syndrome with spastic quadriparesis, microcephaly, startle response and severe global developmental delay in seven patients, caused by a homozygous sequence variation in PLAA (phospholipase A2-activating protein). The mutation joins other complex phospholipid defects known to affect white matter development and maintenance.

In multiple sclerosis, increasing abnormality of the magnetization transfer ratio (MTR) is seen with increasing proximity to the lateral ventricles. Brown et al. identify an abnormal periventricular MTR gradient in individuals with a recent clinically isolated syndrome. Its presence is independent of lesions, and predicts early conversion to multiple sclerosis.

Astrocytes are key players in propelling the development of demyelinating lesions. Ponath et al. report that astroglial myelin phagocytosis is a general phenomenon in CNS pathologies with myelin injury, and further elucidate the functional consequences. Modulating this phagocytic response may have therapeutic potential in conditions with prominent myelin damage.

See Schenck and Mahowald (doi:10.1093/aww329) for a scientific commentary on this article.

Glutamatergic neurons in the pontine sublaterodorsal tegmental nucleus are proposed to generate REM sleep. Valencia Garcia et al. report that their genetic inactivation with AAV-shRNA targeting vGluT2 mRNA does not block REM sleep in rats. Instead it recapitulates REM Sleep Behaviour Disorder, with dream-enacting behaviours and loss of muscle atonia.

See Breen and Lang (doi:10.1093/aww321) for a scientific commentary on this article.

At clinical diagnosis, patients with Parkinson’s disease show a wide range of motor and non-motor features that affect their daily functioning. Darweesh et al. examine trajectories of patients with Parkinson’s disease in the 23 years preceding diagnosis, and observe significant differences versus controls beginning approximately 7 years before diagnosis.

The subthalamic nucleus (STN) has been implicated in impulse control. Voon et al. report that the associative-limbic STN is involved in hasty decisions for short-term gain. STN stimulation in obsessive-compulsive disorder shifts individuals towards less cautious decision making. Limbic and motor function and connectivity are dissociable in the human STN.

There are conflicting data on the origin and progression of neurodegeneration in semantic variant primary progressive aphasia (svPPA). Collins et al. identify a left temporal pole region with consistent atrophy in two patient cohorts. The region’s connectivity in healthy adults predicts the localization and magnitude of distributed atrophy in svPPA.

At best only 30–40% of patients with major depressive disorder experience remission with any given treatment. Crane et al. evaluate neural network and behavioural performance predictors of treatment response, and report that individuals with poorer and less efficient cognitive control benefit more from treatment with antidepressants.

Understanding how antipsychotics exert their effects would allow the development of new treatments and the identification of response markers in psychosis. Crossley et al. show that the global organization of white matter tracts predicts response to treatment. Individuals with a more efficiently wired connectome tend to show better responses.

See McKay and Furl (doi:10.1093/aww323) for a scientific commentary on this article.

How a focal brain injury can lead to Capgras Syndrome, the delusion that a family member has been replaced by an imposter, is unknown. Darby et al. report that such delusions may arise when a lesion is functionally connected to brain regions involved in feelings of familiarity and belief evaluation.

Dorsal column

From the Archives

Letters to the Editor

  • Cover Image

    Cover Image

    issue cover

    Cover image: Spontaneous intracranial hypotension is often treated by epidural blood patches, akin to the Little Dutch Boy who saved his town by plugging a hole in a dyke with his finger. From Wu et al. Factors predicting response to the first epidural blood patch in spontaneous intracranial hypotension. Pp. 344–352

    Cover art by Ta-Yu Wu, MD.

  • Front Matter
  • Table of Contents
  • Back Matter
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