Vestibular rehabilitation in cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS)- A case report.

Background and purpose: Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) is a neurodegenerative disease of the cerebellum. The disease progression is slow, with up to 25% of people diagnosed needing to use a wheelchair after 15 years from diagnosis. Vestibular symptoms arise from centrally-mediated ocular movement degradation and the reduced vestibular-ocular reflex functioning bilaterally. To date, no report has shown an improvement in VOR gain or gait outcome measures in someone with CANVAS after a course of vestibular physical therapy. Case description: A 65-year-old male, Patient X, first noticed symptoms in his fourth decade of life and was diagnosed with (CANVAS) in his seventh decade. Patient X reported numbness and tingling in his hands and feet, decreased ability to perform daily activities, and several falls. Intervention: Patient X completed a four-month course of vestibular physical therapy, including vestibular ocular reflex exercises, balance training, gait training, and the VestAid application for eye gaze compliance monitoring. The Vestaid application uses eyes and facial recognition software to record the percentage of time that the patient kept their eyes on the target. Outcomes: After vestibular therapy, Patient X had a clinically meaningful improvement in gait speed: from 1.02 m/s to 1.13 m/s and in the Functional Gait Assessment from 20/30 to 27/30. Patient X's eye gaze compliance improved from a median of 43% (range 25-68%) to a median of 67% (58-83%). Discussion: This case study demonstrates that vestibular rehabilitation improved eye gaze compliance and functional outcomes in a person living with CANVAS.

Pathways of glycosphingolipid biosynthesis in SW13 cells in the presence and absence of vimentin intermediate filaments.

We reported previously that the incorporation of sugars into glycosphingolipids (GSL) is diminished in SW13 cells that lack a vimentin intermediate filament (IF) network (vim-) compared to vim+ cells. To further analyze the nature of this abnormality, we double-labeled cells with 3H-serine and 14C-sugars. There was no difference between vim+ and vim- cells in the incorporation of serine into GSL, although the usual difference in sugar incorporation was observed. This indicated that the defect in vim- cells was not in the incorporation of sugars into ceramide synthesized de novo by acylation of sphinganine (pathway 1). Sugars can also be incorporated into ceramide synthesized from sphingosine that is derived from catabolism of sphingolipids (pathway 2), and into GSL that recycle through the Golgi apparatus from endosomes (pathway 3). The amount of galactose and glucosamine incorporated into GSL in these three pathways was analyzed by the use of two inhibitors of sphingolipid biosynthesis. beta-Chloroalanine inhibits the de novo synthesis of sphinganine (pathway 1), and fumonisin B1 inhibits the acylation of sphinganine and sphingosine (pathways 1 and 2). We were surprised to observe that in both vim+ and vim- cells only 20-40% of sugar incorporation into GSL took place in pathway 1, and 60-80% of sugar incorporation took place in the recycling pathways. Moreover, in contrast to larger GSL, GlcCer was not synthesized in pathway 3. Our observations indicate that vimentin IF facilitate the recycling of GSL and sphingosine, and that the differences between vim+ and vim- cells are predominantly in pathways 2 and 3. Furthermore, although it is generally believed that virtually all GSL are synthesized in the de novo pathway, these data indicate that the recycling pathways predominate in the incorporation of sugars into GSL in SW13 cells.

Biosynthesis of glycosphingolipids is reduced in the absence of a vimentin intermediate filament network.

Our previous observations on the immunocytochemical colocalization of intermediate filaments and glycosphingolipids led us to analyze the role of filaments in the biosynthesis and intracellular transport of glycosphingolipids. Cells with (vim+) and without (vim-) vimentin intermediate filaments were cloned from the adrenal carcinoma cell line SW13. There was no difference between vim+ and vim- cells in the proportion of newly synthesized C6-NBD-glucosylceramide transported to the plasma membrane. The vim+ cells synthesized glycosphingolipids, especially lactosylceramide and globotriosylceramide, and to a lesser extent GM3 ganglioside, more rapidly than vim- cells. The altered rate of biosynthesis did not result from differences in the levels of the glycosyltransferases that synthesize those compounds. To determine whether the presence of a vimentin network was responsible for the differences in biosynthesis, mouse vimentin cDNA was transfected into vim- cells. Transfected cells that expressed a mouse vimentin network demonstrated a twofold or greater increase in the rate of biosynthesis of neutral glycosphingolipids and gangliosides. There was no difference between vim+ and vim- cells in the synthesis of ceramide or sphingomyelin, or in their content of phospholipids or cholesterol. The nature of the biochemical defect(s) underlying the diminished incorporation of radiolabeled sugars into glycosphingolipids is unclear. Possibilities include alterations in the ultrastructure of the Golgi and/or abnormalities in a portion of the endocytic pathway.

Postcardiotomy confusion and sleep loss.

To examine the relationship between sleep loss and confusion after open-heart surgery, 27 consecutive patients were monitored 1 day preoperatively and 5 days postoperatively with the Folstein Mini-Mental State examination, a modified sleep latency test, and a sleep log. Confusion (low Mini-Mental State scores) peaked on postoperative Days 1 and 2 and correlated with insomnia (sleep time) during the following night but not during the preceding night. The results suggest that sleep loss is not the cause but, rather, a consequence of postcardiotomy confusion. Confusion, not insomnia, should be the focus of treatment.