Dear Editor, We were intrigued to read the article by Martos et al.1 about a boy affected by progressive dystonia, spasticity, retinitis pigmentosa, and psychomotor delay. They labeled this boy as having “HARP”, a term coined almost 3 decades ago to summarize a clinical syndrome of “hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration.”2 As acknowledged in their contribution’s title, “HARP” has long been established as allelic with pantothenate kinase-associated neurodegeneration (PKAN).3,4 We are therefore perplexed as to why the boy’s condition is not merely termed PKAN, and even more so why it is labeled “incomplete HARP syndrome”, justified according to the authors by the failed detection of “hypoprebetalipoproteinemia.” Such redundant as well as nonsensical terminology perpetuates the use of diagnostic terms that convey no relevant meaning, and distracts from focusing on the possible significance, if any, of observations hidden in a seemingly attractive acronym. We initially raised this concern some years ago5 when we explained that the term “hypoprebetalipoproteinemia” had originated in “a bygone era when gel or paper electrophoresis was used to separate plasma lipoproteins.” The “prebetalipoprotein” fraction migrates faster than low-density lipoprotein (LDL, or “betalipoprotein”) and in ultracentrifugally separated plasma corresponds to particles known today, respectively, as lipoprotein (a) [Lp(a)] and very-low-density lipoproteins (VLDL). Modern biochemical methods can precisely quantitate both, eliminating the requirement for semiquantitative electrophoresis.” We emphasized then that “hypoprebetalipoproteinemia” and “aprebetalipoproteinemia” are meaningless from a metabolic perspective and are absent from the lipoprotein literature.5 Neither isolated low plasma VLDL nor Lp(a) have since been connected to pathophysiological consequences, and both research and clinical experience have confirmed that no clinically meaningful entities correspond to these terms. VLDL and its end product LDL each contain one molecule of apolipoprotein B; it is impossible for humans to have isolated VLDL deficiency (i.e., “hypoprebetalipoproteinemia”) without concurrent LDL deficiency. This inappropriately named phenotype has never been documented using modern quantification methods. However, while terms with “..prebeta..” should be discontinued, “abetalipoproteinemia” (ABL, Bassen-Kornzweig syndrome; OMIM #200100) and “hypobetalipoproteinemia” (FHBL1, OMIM #615558; FHBL1, OMIM # 605019) refer to underlying entities that actually do exist and are characterized by concurrent deficiencies of VLDL and LDL particles. Even if only a single additional case6 received the “HARP” label since its creation in 1992,2 the acronym persists despite the

There is evidence that the cognitive system processes human faces faster and more precisely than other stimuli. Also, faces summon visual attention in an automatic manner, as evidenced by efficient, ‘pop-out’ search for face targets amongst homogeneous non-face distractors. Pop-out for faces implies that faces are processed as a basic visual ‘feature’ by specialized face-tuned detectors, similar to the coding of other features (e.g., color, orientation, motion, etc.). However, it is unclear whether such face detectors encode only the global face configuration or both global and local face features. If the former were correct, the face detectors should be unable to support search for a local face feature, rendering search slower relative to non-face stimuli; that is, there would be local feature suppression (LFS) for faces. If the latter was the case, there should be no difference in the processing of local and, respectively, global face features. In two experiments, participants discerned the presence (vs. absence) of a local target defined as a part of either a normal or a scrambled (schematic or realistic) face or of a non-face (Kanizsa diamond or realistic house) configuration. The results consistently showed a robust LFS effect in both reaction times and error rates for face stimuli, and either no difference or even a local feature enhancement effect for the control stimuli. Taken together, these findings indicate that faces are encoded as a basic visual feature by means of globally tuned face detectors.

The occipital and frontal lobes are anatomically distant yet functionally highly integrated to generate some of the most complex behaviour. A series of long associative fibres, such as the fronto-occipital networks, mediate this integration via rapid feed-forward propagation of visual input to anterior frontal regions and direct top-down modulation of early visual processing.Despite the vast number of anatomical investigations a general consensus on the anatomy of fronto-occipital connections is not forthcoming. For example, in the monkey the existence of a human equivalent of the 'inferior fronto-occipital fasciculus' (iFOF) has not been demonstrated. Conversely, a 'superior fronto-occipital fasciculus' (sFOF), also referred to as 'subcallosal bundle' by some authors, is reported in monkey axonal tracing studies but not in human dissections.In this study our aim is twofold. First, we use diffusion tractography to delineate the in vivo anatomy of the sFOF and the iFOF in 30 healthy subjects and three acallosal brains. Second, we provide a comprehensive review of the post-mortem and neuroimaging studies of the fronto-occipital connections published over the last two centuries, together with the first integral translation of Onufrowicz's original description of a human fronto-occipital fasciculus (1887) and Muratoffs report of the `subcallosal bundle' in animals (1893).Our tractography dissections suggest that in the human brain (i) the iFOF is a bilateral association pathway connecting ventro-medial occipital cortex to orbital and polar frontal cortex, (ii) the sFOF overlaps with branches of the superior longitudinal fasciculus (SLF) and probably represents an 'occipital extension' of the SLF, (iii) the subcallosal bundle of Muratoff is probably a complex tract encompassing ascending thalamo-frontal and descending fronto-caudate connections and is therefore a projection rather than an associative tract.In conclusion, our experimental findings and review of the literature suggest that a ventral pathway in humans, namely the iFOF, mediates a direct communication between occipital and frontal lobes. Whether the iFOF represents a unique human pathway awaits further ad hoc investigations in animals. (C) 2012 Elsevier Ltd. All rights reserved.

Chorea-Akanthozytose ist eine seltene Differenzialdiagnose des M. Huntington und wird durch Mutationen des VPS13A-Gens verursacht. Der chronisch progrediente Verlauf beginnt typischerweise zwischen dem 20. und 40. Lebensjahr und ist charakterisiert durch Epilepsie, orofaziale Dyskinesien, Zungenprotrusionsdystonie, choreatische Bewegungsstörung der Extremitäten, des Rumpfes und von Hals und Kopf („Head drops“). Die Erkrankung endet zumeist fatal nach ca. 12 Jahren Krankheitsdauer. Weltweit einzigartig bieten wir seit 2006 eine Westernblot basierte Diagnostikmöglichkeit für diese seltene neurodegenerative Erkrankung an. Bis Ende 2010 sind mehr als 320 Proben von Patienten mit seltenen und ungelösten Bewegungsstörungen aus 20 Ländern weltweit eingegangen. Ca. 30% konnten positiv auf Chorea-Akanthozytose gestestet werden, während hingegen bei etwa 200 Patienten nach wie vor keine Diagnose gestellt werden konnte. Durch die Präselektion des Patientenkollektives auf ungewöhnliche choreatische und dystone Bewegungsstörungen ergibt sich eine Kohorte mit einem mittleren Alter von 46 Jahren (Standardabweichung: 20,2J.; Min: 4,2J.; Max. 87,3J.) und zumeist schon erfolgtem Ausschluss der häufigeren Differenzialdiagnosen wie beispielsweise dem M. Huntington, dem M. Wilson und tardiver Dystonie. Zusammen mit einer standardisierten Beschreibung des klinischen Syndroms sowie einer zumeist ärztlichen Kontaktperson ergibt sich eine Sammlung an hochselektierten DNA-Proben, die bei Bedarf noch weiter eingegrenzt werden können und bei denen ein Bedarf an weiteren Kooperationen besteht.

The basal ganglia participate in anticipatory motor control. The particular role at the different levels of control – from reflexes to reward systems – is however unclear. Studies of grip forces during object manipulation in patients with Parkinson's disease provide mixed evidence: Grip forces successfully anticipated physical object properties in weight-lifting tasks, but multi-finger grasping tasks suggest impaired anticipation. To further explore this issue, we applied a paradigm that had revealed clear deficits of grip force anticipation in a recent study of patients with pure cerebellar diseases(*).

BACKGROUND:Mutation in the progranulin gene (GRN) can cause frontotemporal dementia (FTD). However, it is unclear whether some rare FTD-related GRN variants are pathogenic and whether neurodegenerative disorders other than FTD can also be caused by GRN mutations. OBJECTIVES:To delineate the range of clinical presentations associated with GRN mutations and to define pathogenic candidacy of rare GRN variants. DESIGN:Case-control study. SETTING:Clinical and neuropathology dementia research studies at 8 academic centers. PARTICIPANTS:Four hundred thirty-four patients with FTD, including primary progressive aphasia, semantic dementia, FTD/amyotrophic lateral sclerosis (ALS), FTD/motor neuron disease, corticobasal syndrome/corticobasal degeneration, progressive supranuclear palsy, Pick disease, dementia lacking distinctive histopathology, and pathologically confirmed cases of frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U); and 111 non-FTD cases (controls) in which TDP-43 deposits were a prominent neuropathological feature, including subjects with ALS, Guam ALS and/or parkinsonism dementia complex, Guam dementia, Alzheimer disease, multiple system atrophy, and argyrophilic grain disease. MAIN OUTCOME MEASURES:Variants detected on sequencing of all 13 GRN exons and at least 80 base pairs of flanking introns, and their pathogenic candidacy determined by in silico and ex vivo splicing assays. RESULTS:We identified 58 genetic variants that included 26 previously unknown changes. Twenty-four variants appeared to be pathogenic, including 8 novel mutations. The frequency of GRN mutations was 6.9% (30 of 434) of all FTD-spectrum cases, 21.4% (9 of 42) of cases with a pathological diagnosis of FTLD-U, 16.0% (28 of 175) of FTD-spectrum cases with a family history of a similar neurodegenerative disease, and 56.2% (9 of 16) of cases of FTLD-U with a family history. CONCLUSIONS:Pathogenic mutations were found only in FTD-spectrum cases and not in other related neurodegenerative diseases. Haploinsufficiency of GRN is the predominant mechanism leading to FTD.

Bildgebung bei frontotemporalen Lobärdegenerationen, Neuropathologie, Genetik.