Progressive Unspecified Motor Speech Disorder: A Longitudinal Single Case Study of an Older Subject.

INTRODUCTION: In a few cases, neurodegenerative diseases debut with a speech disorder whose differential diagnosis can be difficult. CASE REPORT: We describe the case of a right-handed woman with a progressive speech impairment, which debuted when she was 80 years old. We report the results of neurological, neuropsychological, and imaging assessments with positron emission tomography (PET) over a period of nine years. Metabolic PET with 18F-FDG was performed at the age of 81 and repeated two years later due to the worsening of symptoms; amyloid PET with 18F-flutemetamol was performed at the age of 86. All PET results were quantitatively analyzed. A speech impairment remained the isolated neurological symptom for a long time, together with a mood disorder. Early FDG-PET showed hypometabolism in the left superior and inferior frontal areas, in the left superior temporal area, and in the right superior frontal area. Two years later, the hypometabolic area was more extensive. Amyloid PET was qualitatively and quantitatively normal. Nine years after the first symptoms, the speech production progressively worsened until complete anarthria, in association with writing impairment onset and signs of behavioral impairments. No signs of motor involvement were found. CONCLUSIONS: A progressive articulatory disorder without an evolution of motor disorders may be a distinct neurological degenerative entity, mainly affecting speech production for very a long time and with a specific early metabolic pattern in brain FDG-PET in the language production area. Monitoring patients with FDG-PET could predict the disease evolution years before a clinical deterioration.

Amnesia of Uncertain Etiology in an Adolescent during COVID-19 Pandemic: A Case Report.

Sudden retrograde memory loss, in the absence of neurological causes, is usually referred to as a dissociative symptom. Dissociative amnesia, defined in the DSM-V as an inability to remember important autobiographical experiences, usually of a traumatic or stressful nature, is however a controversial phenomenon. Few cases with this pattern are described in the scientific literature and still fewer regarding adolescents. The objective of this study was to describe the case of an unexplained sudden memory loss that only partially fits with the criteria for dissociative amnesia, in a juvenile patient aged 16 years, which occurred during the COVID-19 lockdown. After the exclusion of any organic disturbances, 10 days after the clinical onset, a series of psychometric (neuropsychological and psychodiagnostics) tests were administered to the patient. Recent distress associated with COVID-19 lockdown was reported, while no previous significant distress or psychiatric history emerged during the clinical interview, conducted with the patient and parents. Severe disturbances in remote memory tests were registered, while no impairments in cognitive or anterograde amnestic functions were found or personality disorders. The disturbance was diagnosed as "amnesia of uncertain etiology."

Quantification of dimethyl-ifosfamide and its N-deschloropropylated metabolites in mouse plasma by liquid chromatography-tandem mass spectrometry.

Among antitumor oxazaphosphorine drugs, the prodrug ifosfamide (IFO) and its analogs require metabolic activation by specific liver cytochrome P450 (CYP) enzymes to become therapeutically active. New 7,9-dimethyl-ifosfamide analogs have shown greater cytotoxic activity than IFO, whereas side-chain oxidation still occurred leading to monochloroacetone after N-dechloropropylation. A sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay was developed and validated for the simultaneous quantitation of the prodrug 7S,9S-dimethyl-ifosfamide (diMeIFO) and its two inactive metabolites, N(2)- and N(3)-deschloropropyl-dimethylifosfamide (N(2)-DCP-diMeIFO and N(3)-DCP-diMeIFO) in mouse plasma. After protein precipitation with methanol, the analytes were separated by isocratic reversed-phase chromatography with (methanol/ammonium formate pH 5.5, 60:40, v/v) and detected by tandem mass spectrometry using multiple reaction monitoring of transitions ions m/z 289→168 for diMeIFO, m/z 213→168 for N(2)-DCP-diMeIFO, m/z 213→92 for N(3)-DCP-diMeIFO and m/z 261→154 for IFO (internal standard). The calibration curves were linear over the concentration range of 20-10,000ng/mL for the three analytes. Mean extraction recoveries from mouse plasma were 99, 96, 99 and 100% for diMeIFO, N(2)-DCP-diMeIFO, N(3)-DCP-diMeIFO and IFO, respectively. The lower limit of quantitation for diMeIFO and its metabolites was 20 ng/mL in 50 µL plasma. The method was accurate with calculated bias from -5.8 to 4.0% for diMeIFO, from -1.1 to 10.6% for N(2)-DCP-diMeIFO and from -6.9 to 9.8% for N(3)-DCP-diMeIFO, and precise with coefficients of variation lower than 6.8%, 7.8% and 14.3%, respectively. The assay was successfully applied to a preliminary pharmacokinetic study of diMeIFO and of its metabolites in mice.