This study demonstrates the power of NGS of the CSF coupled with a bioinformatic pipeline in the diagnosis of NB.

Cross-correlations between stimuli delivered to peripheral nerves and the discharges of single, voluntarily activated, motor units can provide information about facilitatory and inhibitory projections to single spinal motoneurons in man. The projection frequency, under the given circumstances, of a facilitatory or inhibitory pathway can be obtained from the proportion of the sampled motor units of a given muscle showing the facilitatory or inhibitory effect. Deductions about the shape and relative amplitude of the underlying post-synaptic potentials can be made from the profile of the changes in firing probability. This technique has been used to explore the projections of low threshold muscle afferents to motoneurons of various leg muscles in man. Homonymous facilitation was demonstrated to all the sampled motor units of soleus (SOL), medial gastrocnemius (MG), tibialis anterior (TA) and vastus medialis (VM) and is presumed to represent the effects of the composite muscle spindle group Ia EPSP. Heteronymous facilitation was demonstrated between certain synergists. The projection frequency was less and the magnitude of the change in firing probability was smaller than for homonymous facilitation. SOL motoneurons, however, were not facilitated from low threshold afferents in the medial gastrocnemius nerve. Reciprocal inhibition was demonstrated between certain antagonists. The majority of the sampled motor units of SOL, however, were facilitated from low threshold afferents in the common peroneal nerve. The threshold for this facilitation was higher than for the homonymous facilitation elicited from this nerve and thus a different class of afferents and/or intercalated interneurons may be involved. There are projections across the knee joint in man. Motor units in vastus medialis (VM) were facilitated from low threshold afferents in the common peroneal nerve. It is likely that these reflex connections, which differ from those in other species, reflect the functional relationships between various lower limb muscles in man.

BackgroundAbnormal expanded GGC repeats within the NOTCH2HLC gene has been confirmed as the genetic mechanism for most Asian patients with neuronal intranuclear inclusion disease (NIID). This cross-sectional observational study aimed to characterise the clinical features of NOTCH2NLC-related NIID in China.MethodsPatients with NOTCH2NLC-related NIID underwent an evaluation of clinical symptoms, a neuropsychological assessment, electrophysiological examination, MRI and skin biopsy.ResultsIn the 247 patients with NOTCH2NLC-related NIID, 149 cases were sporadic, while 98 had a positive family history. The most common manifestations were paroxysmal symptoms (66.8%), autonomic dysfunction (64.0%), movement disorders (50.2%), cognitive impairment (49.4%) and muscle weakness (30.8%). Based on the initial presentation and main symptomology, NIID was divided into four subgroups: dementia dominant (n=94), movement disorder dominant (n=63), paroxysmal symptom dominant (n=61) and muscle weakness dominant (n=29). Clinical (42.7%) and subclinical (49.1%) peripheral neuropathies were common in all types. Typical diffusion-weighted imaging subcortical lace signs were more frequent in patients with dementia (93.9%) and paroxysmal symptoms types (94.9%) than in those with muscle weakness (50.0%) and movement disorders types (86.4%). GGC repeat sizes were negatively correlated with age of onset (r=−0.196, p<0.05), and in the muscle weakness-dominant type (median 155.00), the number of repeats was much higher than in the other three groups (p<0.05). In NIID pedigrees, significant genetic anticipation was observed (p<0.05) without repeat instability (p=0.454) during transmission.ConclusionsNIID is not rare; however, it is usually misdiagnosed as other diseases. Our results help to extend the known clinical spectrum of NOTCH2NLC-related NIID.