Validation Study for Non-Invasive Prediction of IDH Mutation Status in Patients with Glioma Using In Vivo 1H-Magnetic Resonance Spectroscopy and Machine Learning.

The isocitrate dehydrogenase (IDH) mutation status is an indispensable prerequisite for diagnosis of glioma (astrocytoma and oligodendroglioma) according to the WHO classification of brain tumors 2021 and is a potential therapeutic target. Usually, immunohistochemistry followed by sequencing of tumor tissue is performed for this purpose. In clinical routine, however, non-invasive determination of IDH mutation status is desirable in cases where tumor biopsy is not possible and for monitoring neuro-oncological therapies. In a previous publication, we presented reliable prediction of IDH mutation status employing proton magnetic resonance spectroscopy (1H-MRS) on a 3.0 Tesla (T) scanner and machine learning in a prospective cohort of 34 glioma patients. Here, we validated this approach in an independent cohort of 67 patients, for which 1H-MR spectra were acquired at 1.5 T between 2002 and 2007, using the same data analysis approach. Despite different technical conditions, a sensitivity of 82.6% (95% CI, 61.2-95.1%) and a specificity of 72.7% (95% CI, 57.2-85.0%) could be achieved. We concluded that our 1H-MRS based approach can be established in a routine clinical setting with affordable effort and time, independent of technical conditions employed. Therefore, the method provides a non-invasive tool for determining IDH status that is well-applicable in an everyday clinical setting.

A comprehensive clinico-radiological, neuropsychological and biomechanical analysis approach to patients with idiopathic normal pressure hydrocephalus.

BACKGROUND: A systematic approach to patients with suspected idiopathic normal pressure hydrocephalus (iNPH) is essential to recognize the subset of patients who may benefit from ventriculoperitoneal shunt surgery (VPS). Quantitative biomechanical analysis of gait and balance (QBAGB) may help objectify the response to the cerebrospinal fluid tap test (CSF-TT) and VPS outcome after 3 months and support identification of candidates for VPS. METHODS: We retrospectively reviewed data from all patients with probable iNPH who 1) underwent clinico-radiological and neuropsychological assessments using validated scales (iNPH Scale and iNPH Radscale) at our centre in the period from January to December 2018; and 2) had completed QBAGB before CSF-TT ('baseline'), shortly after CSF-TT, and at three months after either VPS or conservative treatment. RESULTS: At the time-points 'after CSF-TT' and '3 months', patients with iNPH and VPS (n = 11) significantly improved on the Kiefer Scale score, iNPH Scale total score and gait domain score, as well as in gait velocity and step length measured by QBAGB. In contrast, patients without surgery (n = 10) had unchanged iNPH Scale scores and motor performance throughout. Using data from all patients, we calculated cut-off levels for substantial improvements in gait velocity, step length, and the iNPH Scale domain gait score at the time-point 'after CSF-TT'. CONCLUSION: QBAGB helps to objectify the response to CSF-TT to select candidates for VPS and corroborates clinico-radiological and neuropsychological data derived from validated scales. The QBAGB cut-off values for substantial improvement after CSF-TT need further elucidation in larger, preferably prospective studies.

An fMRI study of training voluntary smooth circular eye movements.

Despite a large number of recent studies, the promise of fMRI methods to produce valuable insights into motor skill learning has been restricted to sequence learning paradigms, or manual training paradigms where a relatively advanced capacity for sensory-motor integration and effector coordination already exists. We therefore obtained fMRIs from 16 healthy adults trained in a new paradigm that demanded voluntary smooth circular eye movements without a moving target. This aimed to monitor neural activation during two possible motor learning processes: (a) the smooth pursuit control system develops a new perceptual-motor relationship and successfully becomes involved in voluntary action in which it is not normally involved or (b) the saccadic system normally used for voluntary eye movement and which only exhibits linear action skill develops new dynamic coordinative control capable of smooth circular movement. Participants were able to improve within half an hour, typically demonstrating saccadic movement with progressively reduced amplitudes, which better approximated smooth circular movement. Activity in the inferior premotor cortex was significantly modulated and decreased during the progress of learning. In contrast, activations in dorsal premotor and parietal cortex along the intraparietal sulcus, the supplementary eye field and the anterior cerebellum did not change during training. Thus, the decrease of activity in inferior premotor cortex was critically related to the learning progress in visuospatial eye movement control.

Hereditary neuropathy with liability to pressure palsies presenting with sciatic neuropathy.

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal-dominant disorder associated with recurrent mononeuropathies following compression or trivial trauma. Reports on sciatic neuropathy as the presenting manifestation of HNPP are very scarce. We report on a 21-year-old previously healthy man who was admitted with sensorimotor deficits in his left leg. He had no history of preceding transient episodes of weakness or sensory loss. Clinical and electrophysiological examinations were consistent with sciatic neuropathy. Cerebrospinal fluid investigation and MRI of the nerve roots, plexus, and sciatic nerve did not indicate the underlying aetiology. When extended electrophysiological tests revealed multiple subclinical compression neuropathies in the upper limbs, HNPP was contemplated and eventually confirmed by genetic testing.