Here we analyzed whether the anti-neoplastic effect of carnosine, which inhibits glycolytic ATP production, can be antagonized by ATP production via oxidative phosphorylation fueled by pyruvate. Therefore, glioblastoma cells were cultivated in medium supplemented with glucose, galactose or pyruvate and in the presence or absence of carnosine. CPI-613 was employed to inhibit the entry of pyruvate into the tricarboxylic acid cycle and 2,4-dinitrophenol to inhibit oxidative phosphorylation. Energy metabolism and viability were assessed by cell based assays and histochemistry.ATP in cell lysates and dehydrogenase activity in living cells revealed a strong reduction of viability under the influence of carnosine when cells received glucose or galactose but not in the presence of pyruvate. CPI-613 and 2,4-dinitrophenol reduced viability of cells cultivated in pyruvate, but no effect was seen in the presence of glucose. No effect of carnosine on viability was observed in the presence of glucose and pyruvate even in the presence of 2,4-dinitrophenol or CPI-613.In conclusion, glioblastoma cells produce ATP from pyruvate via the tricarboxylic acid cycle and oxidative phosphorylation in the absence of a glycolytic substrate. In addition, pyruvate attenuates the anti-neoplastic effect of carnosine, even when ATP production via tricarboxylic acid cycle and oxidative phosphorylation is blocked. We also observed an inhibitory effect of carnosine on the tricarboxylic acid cycle and a stimulating effect of 2,4-dinitrophenol on glycolytic ATP production.

Introduction“Recurrent Vertigo of Childhood” (RVC) has recently replaced the term “Benign Paroxysmal Vertigo of Childhood” and was defined as recurrent spells of vertigo without evidence of a vestibular migraine of childhood (VMC). RVC and VMC are considered the most frequent causes of vertigo and dizziness in children below 18 years of age. Diagnosis might be challenging since clinical features of RVC and VMC may overlap.ObjectiveThis study aims to characterize clinical and instrument-based findings in patients with RVC and to evaluate the course of the disorder.MethodsWe prospectively collected clinical and instrument-based data of children/adolescents younger than 18 years, who presented at the German Center for Vertigo and Balance Disorders (DSGZ) at the LMU University Hospital in Munich. All patients underwent a comprehensive neurological, ocular motor, vestibular and cochlear examination. Furthermore, findings from follow-up examinations were analyzed.ResultsOverall 42 children (24 male and 18 female) with RVC were included in the study. The mean age at diagnosis was 7 ± 3.6 years with a mean onset of symptoms at the age of 5.6 ± 3.4 years. Attack duration ranged between 1 min and 4 h. The most common accompanying symptoms included nausea, vomiting, expression of fear, and falls. Non-migrainous headaches were reported by 11 patients during initial presentation, 7 of whom were later diagnosed with migraine. Female patients showed a higher age at symptom onset, a higher attack frequency, and attack duration. Eleven of the 24 patients seen at a 3.5 year follow-up reported a complete cessation of attacks. Patients still experiencing vertigo attacks had a significantly reduced attack frequency, especially those who implemented at least one prophylactic measure.ConclusionA precise characterization of symptoms is essential for diagnosing children with RVC. Age at symptom onset does not exceed the age of 12. Gender-specific differences should be considered and may further support the evidence of an association with migraine. The disease course of RVC is benign, nevertheless implementing prophylactic measures such as regular exercise, increased fluid intake, sleep hygiene, and relaxation exercises, can improve attack frequency.

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BackgroundThe main clinical presentation of episodic ataxias (EAs) consists of vertigo and dizziness attacks lasting for minutes to hours with widely varying accompanying symptoms. The differentiation of EA and episodic vertigo/dizziness syndromes in childhood and adolescence such as vestibular migraine (VM) and recurrent vertigo of childhood (RVC) can be challenging. Furthermore, only few prospective studies of children/adolescents with EA are available.ObjectiveThis study aims to characterize clinical and instrument-based findings in EA patients under 18 years of age, to delineate the clinical and therapeutic course in EA, and to present potentially new genetic mutations. Furthermore, the study aims to differentiate distinct characteristics between EA, VM, and RVC patients.MethodsWe prospectively collected clinical and instrument-based data of patients younger than 18 years, who presented at the German Center for Vertigo and Balance Disorders (DSGZ) at the LMU University Hospital in Munich with EA, VM, or RVC between January 2016 and December 2021. All patients underwent a comprehensive evaluation of neurological, ocular-motor, vestibular and cochlear function, including video-oculography with caloric testing, video head impulse test, vestibular evoked myogenic potentials, posturography, and gait analysis.ResultsTen patients with EA, 15 with VM, and 15 with RVC were included. In EA the main symptoms were vertigo/dizziness attacks lasting between 5 min and 12 h. Common accompanying symptoms included walking difficulties, paleness, and speech difficulties. Six EA patients had a previously unknown gene mutation. In the interictal interval all EA patients showed distinct ocular-motor deficits. Significant differences between EA, VM, and RVC were found for accompanying symptoms such as speech disturbances and paleness, and for the trigger factor “physical activity”. Furthermore, in the interictal interval significant group differences were observed for different pathological nystagmus types, a saccadic smooth pursuit, and disturbed fixation suppression.ConclusionBy combining clinical and ocular-motor characteristics we propose diagnostic criteria that can help to diagnose EA among children/adolescents and identify patients with EA even without distinct genetic findings. Nevertheless, broad genetic testing (e.g., next generation sequencing) in patients fulfilling the diagnostic criteria should be conducted to identify even rare or unknown genetic mutations for EA.