[Vanishing white matter disease, a rare leukodystrophy with mutation in the EIF2B5 gene]. / Eltuno fehérállomány-betegség, a leukodystrophiák ritka altípusa az EIF2B5 gén mutációjával.

Background - Leukodystrophies, a hete­ro­­ge­neous group of brain and spinal cord dis­orders, often pose challenges in es­tab­li­shing molecular etiology. Vanishing White Matter Disease (VWMD) is a rare sub­type of leu­ko­dys­trophies presenting with characteristic clinical and MRI features, ne­ver­theless, achieving diag­nostic certainty requires genetic studies.

Case presentation - Our patient is a nine year old girl, who developed progressive gait difficulties at around 3-4 years of age. Her brain MRI showed confluent lesions with in­­creased signal intensity in the cerebral and cerebellar white matter on T2/FLAIR se­quen­ces, within which hypointense regions ap­peared with signal intensity resembling that of the cerebrospinal fluid on T1 sequences. Whole exome sequencing identified a homozygous likely pathogenic variant within the EIF2B5 gene in the proband, which was present in a heterozygous state in both asymptomatic parents. Having the clinical and molecular genetic diagnosis established, we explored therapeutic possibilities for the patient.

Conclusion - VWMD is a severe form of leukodystrophies with little or no disease modifying therapy available until recently. A better understanding of its molecular pathogenesis offers some hope for new inventive therapies. 

Long term follow-up study of non-invasive brain stimulation (NBS) (rTMS and tDCS) in Parkinson's disease (PD). Strong age-dependency in the effect of NBS.

BACKGROUND: Transcranial magnetic stimulation (rTMS) may influence the progression of PD compared with levodopa. The long term mind modification effect of repeated rTMS and tDCS is not known, nor are the predictors for the effect of NBS. OBJECTIVE/HYPOTHESIS: We hypothesized that the regularly repeated rTMS would decrease the development of PD. Later, the treatment protocol was completed with transcranial direct current stimulation (tDCS), supposing that there is an add-on effect. NBS may differently influence motor and mental aspects of the disease. METHODS: Thirty patients with PD were followed for 3.5 years in an open study. They were stimulated with 1 Hz rTMS every half year for 1.5 years. After that the tDCS was add to the stimulation over both sides of the cerebellum for the next 2 years. UPDRS, Trail Making Test and dual tests were used. The linear regression lines of score systems and percentage of yearly increment were counted, analyzed by ANOVA. RESULTS: The yearly progression rate for UPDRS total was 2% for 3.5 years, 0.6% ≤65 years, 3.6% >65 years. The increment was around zero during the rTMS + tDCS stimulations in patients ≤65 years. The slope of the equation showed the same tendency. The individual sensitivity to the NBS was high. tTMS and tDCS >65 yrs improved pathological executive function (p < 0.0001). CONCLUSION: The motor ability in PD was maintained at the same level in patients ≤65 years with NBS for the 3.5 years in contrast to patients >65 years. The cognitive function of patients >65 yrs was favorable influenced by rTMS and tDCS. Age is the main predictor of the effect of NBS. rTMS and tDCS can slow the progression of PD without any side effects but in an age-dependent way.

[Nusinersen in the treatment of spinal muscular atrophy]. / Nusinersen a spinalis izomatrophia kezelésében.

Until recently, the diagnosis of spinal muscular atrophy (SMA) has been associated with severe life-long motor disability in adults and with early death in infants. The new experimental therapeutic approaches of the last few years have become more and more promising, while nusinersen was approved for the treatment of SMA in December 2016 in the USA, and in May 2017 in Hungary. Our paper presents mechanisms and clinical benefits of this new medication, and highlights some of the other therapeutic strategies still in experimental stages.