AZATAX: Acetazolamide safety and efficacy in cerebellar syndrome in PMM2 congenital disorder of glycosylation (PMM2-CDG).

OBJECTIVE: Phosphomannomutase deficiency (PMM2 congenital disorder of glycosylation [PMM2-CDG]) causes cerebellar syndrome and strokelike episodes (SLEs). SLEs are also described in patients with gain-of-function mutations in the CaV2.1 channel, for which acetazolamide therapy is suggested. Impairment in N-glycosylation of CaV2.1 promotes gain-of-function effects and may participate in cerebellar syndrome in PMM2-CDG. AZATAX was designed to establish whether acetazolamide is safe and improves cerebellar syndrome in PMM2-CDG. METHODS: A clinical trial included PMM2-CDG patients, with a 6-month first-phase single acetazolamide therapy group, followed by a randomized 5-week withdrawal phase. Safety was assessed. The primary outcome measure was improvement in the International Cooperative Ataxia Rating Scale (ICARS). Other measures were the Nijmegen Pediatric CDG Rating Scale (NPCRS), a syllable repetition test (PATA test), and cognitive scores. RESULTS: Twenty-four patients (mean age = 12.3 ± 4.5 years) were included, showing no serious adverse events. Thirteen patients required dose adjustment due to low bicarbonate or asthenia. There were improvements on ICARS (34.9 ± 23.2 vs 40.7 ± 24.8, effect size = 1.48, 95% confidence interval [CI] = 4.0-7.6, p < 0.001), detected at 6 weeks in 18 patients among the 20 responders, on NPCRS (95% CI = 0.3-1.6, p = 0.013) and on the PATA test (95% CI = 0.5-3.0, p = 0.006). Acetazolamide improved prothrombin time, factor X, and antithrombin. Clinical severity, epilepsy, and lipodystrophy predicted greater response. The randomized withdrawal phase showed ICARS worsening in the withdrawal group (effect size = 1.46, 95% CI = 2.65-7.52, p = 0.001). INTERPRETATION: AZATAX is the first clinical trial of PMM2-CDG. Acetazolamide is well tolerated and effective for motor cerebellar syndrome. Its ability to prevent SLEs and its long-term effects on kidney function should be addressed in future studies. Ann Neurol 2019;85:740-751.

Length of illness does not predict cognitive dysfunction in chronic fatigue syndrome.

Neuropsychological studies have shown cognitive impairment in chronic fatigue syndrome (CFS), particularly in information-processing speed. The aim of this study was to examine the evolution of cognitive impairment in CFS. The evolution is one of the most disabling aspects of the CFS, and it has received little attention in the literature. Fifty-six women with CFS were assessed with neuropsychological tests. Patients were divided into three groups based on the duration of the disease. There were no differences between groups in terms of cognitive function. The cognitive impairment in CFS was not found to be more severe with longer disease duration. These data suggest that there is no progressive cognitive impairment in patients with CFS. Therefore, the cognitive deficits in CFS should be treated with cognitive rehabilitation programs focused on improving emotional distress associated to the illness and on promoting functional abilities.

[The role of depression in cognitive impairment in patients with chronic fatigue syndrome]. / El rol de la depresión en el déficit cognitivo del paciente con síndrome de fatiga crónica.

BACKGROUND AND OBJECTIVE: To analyze the role of depression in cognitive deficits of patients with chronic fatigue syndrome (CFS). PATIENTS AND METHODS: 57 women with CFS were assessed by neuropsychological tests that included measures of attention: CalCap, Mental control of the WMS-III, PASAT, forward and backward digits (WAIS-III), symbol digit modalities test (SDMT); executive functions: Stroop Test, Trail Making Test (TMT A y B), FAS, Tower of London; memory: Auditory-Verbal Learning Test (AVL), Rey Complex Figure (RCF), and psychomotor skills: Grooved Pegboard. The raw scores on the tests were adjusted according to normative data and transformed to T scores. The sample was divided into two groups based on the presence or absence of depression, assessed by clinical interview and administration of the Hospital Anxiety and Depression Scale (HADS). This study compared neuropsychological test scores between the two groups. RESULTS: CFS patients showed cognitive deficit in attention and executive functions, regardless of the presence of depression. There were no significant differences between the two CFS groups. CONCLUSIONS: The cognitive impairments in patients with CFS are not secondary to the presence of depression. These results should be taken into account in the implementation of therapeutic programs in these patients.

El rol de la depresión en el déficit cognitivo del paciente con síndrome de fatiga crónica / The role of depression in cognitive inpairment in patients with chronic fatigue syndrome

Fundamento y objetivo: Analizar el rol de la depresión en el déficit cognitivo del paciente con síndrome de fatiga crónica (SFC). Pacientes y método: Un total de 57 mujeres con diagnóstico de SFC fueron evaluadas mediante tests neuropsicológicos que incluían medidas de atención (CalCap, Control Mental del WMS-III, PASAT, dígitos directos e inversos del WAIS-III y symbol digit modalities test [SDMT]) funciones ejecutivas (test Stroop, Trail Making Test [TMT A y B], FAS y Torre de Londres), memoria (Test de Aprendizaje Auditivo-Verbal [TAAVL] y Test de la Figura Compleja de Rey [FCR]) y velocidad psicomotora (Grooved Pegboard). Las puntuaciones directas fueron ajustadas de acuerdo a datos normativos y transformadas a puntuaciones típicas. La muestra fue dividida en dos grupos en función de la presencia o no de depresión, evaluada mediante entrevista clínica y la administración de la Escala Hospitalaria de Ansiedad y Depresión (HAD). Las puntuaciones de los test neuropsicológicos fueron comparadas entre ambos grupos de pacientes.Resultados: Los pacientes con SFC presentaron déficit cognitivo en funciones atencionales y ejecutivas, independientemente de la presencia de depresión. No se observaron diferencias significativas en funciones cognitivas entre los dos grupos de pacientes.Conclusiones: Estos datos sugieren que el déficit cognitivo que presentan los pacientes con SFC no es secundario a la depresión. Se debería tener en cuenta este resultado en la implementación de un programa terapéutico en estos enfermos (AU)

Background and objective: To analyze the role of depression in cognitive deficits of patients with chronic fatigue syndrome (CFS). Patients and methods: 57 women with CFS were assessed by neuropsychological tests that included measures of attention: CalCap, Mental control of the WMS-III, PASAT, forward and backward digits (WAIS-III), symbol digit modalities test (SDMT); executive functions: Stroop Test, Trail Making Test (TMT A y B), FAS, Tower of London; memory: Auditory-Verbal Learning Test (AVL), Rey Complex Figure (RCF), and psychomotor skills: Grooved Pegboard. The raw scores on the tests were adjusted according to normative data and transformed to T scores. The sample was divided into two groups based on the presence or absence of depression, assessed by clinical interview and administration of the Hospital Anxiety and Depression Scale (HADS). This study compared neuropsychological test scores between the two groups.Results: CFS patients showed cognitive deficit in attention and executive functions, regardless of the presence of depression. There were no significant differences between the two CFS groups.Conclusions: The cognitive impairments in patients with CFS are not secondary to the presence of depression. These results should be taken into account in the implementation of therapeutic programs in these patients (AU)