Evaluation of the Patients with the Diagnosis of Pontocerebellar Hypoplasia: A Multicenter National Study.

Pontocerebellar hypoplasia (PCH) is a heterogeneous group of neurodegenerative disorders characterized by hypoplasia and degeneration of the cerebellum and pons. We aimed to identify the clinical, laboratory, and imaging findings of the patients with diagnosed PCH with confirmed genetic analysis. We collected available clinical data, laboratory, and imaging findings in our retrospective multicenter national study of 64 patients with PCH in Turkey. The genetic analysis included the whole-exome sequencing (WES), targeted next-generation sequencing (NGS), or single gene analysis. Sixty-four patients with PCH were 28 female (43.8%) and 36 (56.3%) male. The patients revealed homozygous mutation in 89.1%, consanguinity in 79.7%, pregnancy at term in 85.2%, microcephaly in 91.3%, psychomotor retardation in 98.4%, abnormal neurological findings in 100%, seizure in 63.8%, normal biochemistry and metabolic investigations in 92.2%, and dysmorphic findings in 51.2%. The missense mutation was found to be the most common variant type in all patients with PCH. It was detected as CLP1 (n = 17) was the most common PCH related gene. The homozygous missense variant c.419G > A (p.Arg140His) was identified in all patients with CLP1. Moreover, all patients showed the same homozygous missense variant c.919G > T (p.A307S) in TSEN54 group (n = 6). In Turkey, CLP1 was identified as the most common causative gene with the identical variant c.419G > A; p.Arg140His. The current study supports that genotype data on PCH leads to phenotypic variability over a wide phenotypic spectrum.

Chromosomal microarray and exome sequencing in unexplained early infantile epileptic encephalopathies in a highly consanguineous population.

AIM: To identify genetic causes for early infantile epileptic encephalopathies (EIEE) in Turkish children with mostly consanguineous parents. METHODS: In a selected EIEE group (N = 59) based on results of nongenetic and initial genetic testing with unexplained etiology, 49 patients underwent array-based comparative genomic hybridization (aCGH) and 49 patients underwent whole exome sequencing (WES) including 39 with negative aCGH results and 10 with WES-only. RESULTS: Diagnostic yield of aCGH and WES for pathogenic or likely pathogenic variants was 14.3% and 38.8%, respectively. Including de novo variants of uncertain significance linked to compatible phenotypes, increased the diagnostic yield of WES to 61.2%. Out of 38 positive variants, 18 (47.4%) were novel and 16 (42.1%) were de novo. Twenty-one (56.8%) patients had recessive variants inherited from mostly consanguineous healthy parents (85.7%). Fourteen (37.8%) of patients with diagnostic results had positive variants in established EIEE genes. Seizures started during neonatal period in 32.4% patients. Posture or movement disorders were comorbid with EIEE in 40.5% of diagnosed patients. We identified treatable metabolic disorders in 8.1% of patients and pathogenic variants in genes which support using targeted medicine in 19% of patients. CONCLUSIONS: Detailed electro-clinical phenotyping led to expansion of some of the known phenotypes with non-neurological and neurological findings in addition to seizures, as well as suggestion of candidate genes (SEC24B, SLC16A2 and PRICKLE2) and a copy number variant (microduplication of Xp21.1p11.4). The high ratio of recessive inheritance could be important for family counseling.

How do presentation age and CSF opening pressure level affect long-term prognosis of pseudotumor cerebri syndrome in children? Experience of a single tertiary clinic.

BACKGROUND: Diagnosis and treatment of pseudotumor cerebri syndrome in children is still a challenge for clinicians. The aim of this study is to reveal the influence of presentation age and CSF opening pressure on long-term prognosis of pseudotumor cerebri and share our clinical data of the very young age (≤ 5-year) group. METHOD: This retrospective study includes the patients followed by the Marmara University Pediatric Neurology Clinic between years 2012 and 2020 diagnosed with definite, probable, or suggestive pseudotumor cerebri syndrome according to modified Friedman criteria. Patients were classified into three groups according to presentation age: group 1: ≤ 5 years old; group 2: 6-10 years; and group 3 > 10 years old. CSF opening pressure was also categorized into three groups as CSF < 20 cmH20; CSF 20-30 cmH20; and CSF > 30 cmH20. RESULTS: One hundred three patients, 62.1% female (n = 64), were enrolled in the study. Group 1 consisted of 16 patients (60% male), group 2 consisted of 30 patients (63.3% female), and group 3 consisted of 57 patients (66.7% female). The mean CSF opening pressure did not differ between the three age groups in our study (p > 0.05). Treatment response was not correlated with CSF opening pressure. Papilledema presence and level of CSF opening pressure were independent of age (p > 0.05). CONCLUSIONS: Age at presentation and CSF opening pressure at diagnosis are not any predictive factors that influence long-term prognosis of pseudotumor cerebri syndrome in children. Evaluation and follow-up of children should be done in personalized approach.

Respiratory outcome of spinal muscular atrophy type 1 patients treated with nusinersen.

BACKGROUND: Respiratory failure is the leading cause of mortality in spinal muscular atrophy type 1 (SMA1) children. The current study aims to evaluate the effect of nusinersen treatment on respiratory outcome of the patients with SMA1. METHODS: In this retrospective, single-center study, 52 SMA1 patients treated with nusinersen were included in the analysis. Patients were divided into two groups based on their age at the time of their first nusinersen treatment (Group 1: ≤6 months, Group 2: >6 months). Respiratory outcome on the 180th day of treatment is defined as the type of ventilation support (spontaneous breathing, noninvasive ventilation (NIV), and tracheostomized or intubated on invasive mechanical ventilation). Demographic data, respiratory outcome, and Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders scores were obtained from medical records. RESULTS: On the 180th day of treatment, 46 of the 52 (88.4%) children were alive. Prevalence of the mortality was similar in both groups (P = 0.65). The comparison of respiratory outcome in patients between group 1 and group 2 was as follows: spontaneous breathing, 7 (43.7%) versus 4 (13.3%) (P = 0.03); NIV <16 h/day, 3 (18.7%) versus 4 (13.3%) (P = 0.68); invasive mechanical ventilation, 6 (37.5%) versus 22 (73.3%) (P = 0.01). There were no patients using NIV ≥16 h/day. There were significant improvements in Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders scores of the patients at day 180 in comparison with the baseline (P < 0.001). CONCLUSIONS: Early initiation of nusinersen treatment in SMA1 patients may alter the disease's natural course.

Genomic variants causing mitochondrial dysfunction are common in hereditary lower motor neuron disease.

Hereditary lower motor neuron diseases (LMND) other than 5q-spinal muscular atrophy (5q-SMA) can be classified according to affected muscle groups. Proximal and distal forms of non-5q-SMA represent a clinically and genetically heterogeneous spectrum characterized by significant overlaps with axonal forms of Charcot-Marie-Tooth (CMT) disease. A consensus for the best approach to molecular diagnosis needs to be reached, especially in light of continuous novel gene discovery and falling costs of next-generation sequencing (NGS). We performed exome sequencing (ES) in 41 families presenting with non-5q-SMA or axonal CMT, 25 of which had undergone a previous negative neuromuscular disease (NMD) gene panel analysis. The total diagnostic yield of ES was 41%. Diagnostic success in the cohort with a previous NMD-panel analysis was significantly extended by ES, primarily due to novel gene associated-phenotypes and uncharacteristic phenotypic presentations. We recommend early ES for individuals with hereditary LMND presenting uncharacteristic or significantly overlapping features. As mitochondrial dysfunction was the underlying pathomechanism in 47% of the solved individuals, we highlight the sensitivity of the anterior horn cell and peripheral nerve to mitochondrial imbalance as well as the necessity to screen for mitochondrial disorders in individuals presenting predominant lower motor neuron symptoms.

Relationships Among 3 Movement Analysis Tests in Preterm Infants.

PURPOSE: To investigate the relationships among the Infant Motor Profile (IMP), the Neuro-Sensory Motor Developmental Assessment (NSMDA), and the Alberta Infant Motor Scale (AIMS) in prematurely born infants. METHODS: Sixty-one preterm infants with a birth weight under 2500 g were assessed by the IMP, the NSMDA, and the AIMS. RESULTS: There was a significant correlation between the IMP total score and the AIMS percentile and between the IMP total score and the NSMDA functional levels. There were significant correlations between the AIMS percentile age and the NSMDA functional levels and between the AIMS total scores and the IMP total scores. In the infants with atypical development, the relationship was significant between the AIMS and the IMP; however, there was no relationship between the IMP and the NSMDA. CONCLUSIONS: The 3 movement analysis tests are related. The IMP was found to be consistent with other movement analysis tests.

Transient Splenial Lesion of the Corpus Callosum Related to Migraine with Aura in a Pediatric Patient.

BACKGROUND: Transient splenial lesions of the corpus callosum are rare radiological findings first described in association with epilepsy, antiepileptic drugs and viral encephalitis. However, subsequently more cases were described associated with diverse clinical conditions. CASE REPORT: We describe a 13-year-old girl suffering from migraine with aura presenting with headache, right-sided hemiparesis and encephalopathy. Brain magnetic resonance imaging revealed an ovoid lesion in the splenium of the corpus callosum. The patient's neurological symptoms resolved within 3 days without therapy and the lesion disappeared in follow up magnetic resonance images obtained 3 weeks after the onset of the symptoms. RESULTS: Migraine with aura was considered to be the cause of the lesion. To our knowledge the present case is the first report of a pediatric patient with a diagnosis of migraine with aura presenting with hemiparesis and encephalopathy. CONCLUSIONS: A diagnosis of transient lesion of the corpus callosum should be suspected in patients with migraine with aura presenting with hemiparesis and encephalopathy. A mild course and a good prognosis might be expected in the presence of a splenial lesion of the corpus callosum.

Neural tube defect family with recessive trait linked to chromosome 9q21.12-21.31.

PURPOSE: Meningomyelocele is one of the most common and socioeconomically, psychologically, and physically debilitating neurodevelopmental diseases. A few chromosomal locus and genes have been identified as responsible for the disease; however, clear evidence still needs to be produced. This study aimed to show evidence of a strong genetic linkage in a novel chromosomal locus in a family with this neural tube defect. METHODS: We identified a neural tube defect family in eastern Turkey, where two of six offspring had operations due to thoracolumbar meningomyelocele. The parents were of a consanguineous marriage. We collected venous blood from six offspring of the family. Whole genome linkage analysis was performed in all offspring. RESULTS: A theoretical maximum logarithm of an odds score of 3.16 was identified on chromosome 9q21.12-21.31. This result shows a strong genetic linkage to this locus. CONCLUSIONS: Our results identified a novel chromosomal locus related to meningomyelocele and provide a base for further investigations toward the discovery of a new causative gene.

Gómez-López-Hernández Syndrome: A Rare Cause of Bilateral Nonscarring Alopecia.

Gómez-López-Hernández syndrome is a rare neurocutaneous disorder characterized by the triad of rhombencephalosynapsis, parietal alopecia, and trigeminal anesthesia. We report a 16-year-old girl with bilateral parietotemporal alopecia in whom cranial magnetic resonance imaging revealed rhombencephalosynapsis, suggesting a diagnosis of Gómez-López-Hernández syndrome. Neurologic examination and neuroimaging may be warranted in select patients with parietal alopecia to exclude this uncommon entity.

Effect of antiepilepsy drug therapy on ventricular function in children with epilepsy: a tissue Doppler imaging study.

Impaired cardiac myocardial function may contribute to the risk for sudden unexpected death of a patient with epilepsy. This study aimed to investigate the effect of antiepilepsy drugs (AEDs) on cardiac function in pediatric epileptic patients using standard and tissue Doppler imaging (TDI) echocardiography. This hospital-based, prospective cross-sectional study investigated 52 epileptic children (mean age 9.3 ± 3.1 years) treated with AEDs (duration 2.4-10.0 years) and 36 healthy children (mean age 9.5 ± 4.0 years). In the epilepsy group, standard echocardiography showed increased left ventricular (LV) end-diastolic and end-systolic diameters, an increased LV mass index, and preserved ejection fraction. The patients also exhibited increased mitral peak A-wave velocity and mitral E-wave deceleration time as well as a decreased mitral E/A ratio. The E/Em ratio was significantly higher in the epilepsy group (5.6 ± 1.2) than in the control group (5.2 ± 1.1) (p = 0.016). In the epilepsy group, TDI showed an increased isovolumetric relaxation time and myocardial performance index (MPI). It also exhibited decreased early diastolic velocity (Em) and a decreased mitral annular displacement index in these patients. There were positive correlations between the LV lateral wall MPI (r = 0.231), septal MPI (r = 0.223), and LV mass index (p < 0.05) but no correlation with the duration of AED treatment. The authors detected subclinical ventricular dysfunction associated with AEDs at a preclinical stage. They suggest that TDI can be useful for determining the short- and long-term cardiac effects of AEDs.

Optic neuritis in Turkish children and adolescents: A multicenter retrospective study.

BACKGROUND: Various etiologies may underlie optic neuritis, including autoantibody-mediated disorders described in the last decade. We re-examined demographic, clinical, laboratory features and prognostic factors in pediatric patients with autoimmune optic neuritis according to current knowledge. METHODS: Cases of pediatric ON from 27 centers in Türkiye diagnosed between 2009 and 2022 were included for retrospective evaluation. RESULTS: The study included 279 patients, 174 females and 105 males, with a female-to-male ratio of 1.65. The average age at onset was 12.8 ± 3.4 years, and mean follow-up, 2.1 years (range: 1-12.1 years). Patients <10 years old were grouped as "prepubertal" and those ≥10 years old as "others". The diagnoses made at the end of follow-up were multiple sclerosis associated optic neuritis (n = 90, 32.3 %), single isolated optic neuritis (n = 86, 31 %), clinically isolated syndrome (n = 41, 14.7 %), myelin oligodendrocyte glycoprotein antibody associated optic neuritis (n = 22, 7.9 %), and relapsing isolated optic neuritis (n = 18, 6.5 %). Predominant diagnoses were myelin oligodendrocyte glycoprotein antibody associated optic neuritis and acute disseminated encephalomyelitis associated optic neuritis in the prepubertal group and multiple sclerosis associated optic neuritis in the older group. Recurrences were observed in 67 (24 %) patients, including 28 with multiple sclerosis associated optic neuritis, 18 with relapsing isolated optic neuritis, 11 with myelin oligodendrocyte glycoprotein antibody associated optic neuritis, 8 with aquaporin-4 antibody related optic neuritis, and 2 with chronic relapsing inflammatory optic neuropathy. Recurrences were more common among female patients. Findings supporting the diagnosis of multiple sclerosis included age of onset ≥ 10 years (OR=1.24, p = 0.027), the presence of cranial MRI lesions (OR=26.92, p<0.001), and oligoclonal bands (OR=9.7, p = 0.001). Treatment in the acute phase consisted of intravenous pulse methylprednisolone (n = 46, 16.5 %), pulse methylprednisolone with an oral taper (n = 212, 76 %), and combinations of pulse methylprednisolone, plasmapheresis, or intravenous immunoglobulin (n = 21, 7.5 %). Outcome at 12 months was satisfactory, with 247 out of 279 patients (88.5 %) demonstrating complete recovery. Thirty-two patients exhibited incomplete recovery and further combination treatments were applied. Specifically, patients with relapsing isolated optic neuritis and aquaporin-4 antibody related optic neuritis displayed a less favorable prognosis. CONCLUSION: Our results suggest optic neuritis is frequently bilateral in prepubertal and unilateral in peri­ or postpubertal patients. Age of onset 10 or older, presence of oligoclonal bands, and brain MRI findings reliably predict the development of multiple sclerosis. The risk of developing multiple sclerosis increases mostly during the second and third years of follow-up. Relapsing isolated optic neuritis remains a separate group where the pathogenesis and outcome remain unclear. Investigation of predisposing and diagnostic biomarkers and long follow-up could help to define this group.

Depression, anxiety, and sleep quality of caregivers of children with spinal muscular atrophy.

BACKGROUND: The aim of this study was to evaluate the prevalence of anxiety, depression, sleep, and associated factors in caregivers of children with spinal muscular atrophy (SMA). MATERIALS AND METHODS: Beck Depression Inventory (BDI), the State-Trait Anxiety Inventory-State (STAI-S), the State-Trait Anxiety Inventory-Trait (STAI-T), and Pittsburgh Sleep Quality Index (PSQI) were used to assess the anxiety, depression, and sleep quality of the caregivers of children with SMA. Higher scores indicated worse outcome for all three questionnaires. RESULTS: Fifty-six caregivers of children with SMA were included in the study. Median age of children was 6 (3.2-10) years and mean age of the caregivers was 37.0 ± 6.5 years. Median scores of the BDI, STAI-S, STAI-T, and PSQI were 12 (7.2-17), 35.5 (31-44), 40.5 (35-48), and 7.0 (5.0-10.0), respectively. There was a positive correlation between BDI and PSQI scores (p < 0.05). There was a negative correlation between the age of the caregivers and PSQI, BDI, STAI-T scores (p = 0.01, r = -0.341; p = 0.006, r = -0.364; p = 0.003, r = -0.395, respectively). There was a negative correlation between the age of the patients and the PSQI scores of the caregivers (p = 0.01, r = -0.33). There was a negative correlation between BDI scores and household income (p = 0.01, r = -0.34). CONCLUSION: Caregivers of children with SMA had elevated depression and anxiety levels and they also had decreased sleep quality. Economic and social support resources are needed to help caregivers of those children.

The outcome of two SMA cases treated with nusinersen at seven hours and at three days of life: the earliest ever.

New molecular therapies are available for the treatment of spinal muscular atrophy (SMA) but early intervention is required. We report two cases that were diagnosed prenatally, where treatment with nusinersen was initiated within 7 h and three days respectively. The children were followed up for 13 months and almost six years respectively. Both children have developed within entirely normal centiles, indicating that initiating treatment immediately after birth, as in these cases, is essential for a good outcome.

Re-examining the characteristics of pediatric multiple sclerosis in the era of antibody-associated demyelinating syndromes.

BACKGROUND: The discovery of anti-myelin oligodendrocyte glycoprotein (MOG)-IgG and anti-aquaporin 4 (AQP4)-IgG and the observation on certain patients previously diagnosed with multiple sclerosis (MS) actually have an antibody-mediated disease mandated re-evaluation of pediatric MS series. AIM: To describe the characteristics of recent pediatric MS cases by age groups and compare with the cohort established before 2015. METHOD: Data of pediatric MS patients diagnosed between 2015 and 2021 were collected from 44 pediatric neurology centers across Türkiye. Clinical and paraclinical features were compared between patients with disease onset before 12 years (earlier onset) and ≥12 years (later onset) as well as between our current (2015-2021) and previous (<2015) cohorts. RESULTS: A total of 634 children (456 girls) were enrolled, 89 (14%) were of earlier onset. The earlier-onset group had lower female/male ratio, more frequent initial diagnosis of acute disseminated encephalomyelitis (ADEM), more frequent brainstem symptoms, longer interval between the first two attacks, less frequent spinal cord involvement on magnetic resonance imaging (MRI), and lower prevalence of cerebrospinal fluid (CSF)-restricted oligoclonal bands (OCBs). The earlier-onset group was less likely to respond to initial disease-modifying treatments. Compared to our previous cohort, the current series had fewer patients with onset <12 years, initial presentation with ADEM-like features, brainstem or cerebellar symptoms, seizures, and spinal lesions on MRI. The female/male ratio, the frequency of sensorial symptoms, and CSF-restricted OCBs were higher than reported in our previous cohort. CONCLUSION: Pediatric MS starting before 12 years was less common than reported previously, likely due to exclusion of patients with antibody-mediated diseases. The results underline the importance of antibody testing and indicate pediatric MS may be a more homogeneous disorder and more similar to adult-onset MS than previously thought.

Neurodevelopmental Findings and Epilepsy in Malformations of Cortical Development.

AIM: The purpose of this study is to classify the malformations of cortical development in children according to the embryological formation, localization, and neurodevelopmental findings. Seizure/epilepsy and electrophysiological findings have also been compared. MATERIAL AND METHODS: Seventy-five children (age: 1 month-16.5 years; 56% male) followed with the diagnosis of malformation of cortical development, in Marmara University Pendik Research and Educational Hospital Department of Pediatric Neurology, were included in the study. Their epilepsy characteristics, electroencephalogram (EEG) findings, and prognosis were reported. Neurodevelopmental characteristics were evaluated by the Bayley Scales of Infant and Toddler Development (Bayley-III) for the ages of 0-42 months (n = 30); the Denver Developmental Screening Test-II (DDST-II) for ages 42 months-6 years (n = 11); and the Wechsler Intelligence Scales for Children (WISC-R), used for children 6 years and older (n = 34). RESULTS: The patients were classified as 44% premigrational (14.6% microcephaly, 24% tuberous sclerosis, 2.7% focal cortical dysplasia, 1.3% hemimegalencephaly, and 1.3% diffuse cortical dysgenesis); 17.3% migrational (14.6% lissencephaly, 2.7% heterotopia); and 38.6% postmigrational (14.6% schizencephaly, 24% polymicrogyria) developmentally. According to involved area, the classification was 34.7% hemispheric/multilobar, 33.3% diffuse, and 32% focal. Seventy-five percent of the patients had a history of epilepsy, and 92% were resistant to treatment. The seizures started before the age of 12 months in diffuse malformations, and epileptic encephalopathy was more common in microcephaly with a rate of 80% and lissencephaly with a rate of 54.5% in the first EEGs. Ninety-five percent of patients had at least one level of neurodevelopmental delay detected by DDST/Bayley-III; this was more common in patients with accompanying epilepsy (P < .05). As seen more commonly in patients with diffuse pathologies and intractable frequent seizures, mental retardation was detected by WISC-R in 64.5% of patients (P < .05). CONCLUSION: In cases with cortical developmental malformation, epilepsy/EEG features and neurodevelopmental prognosis can be predicted depending on the developmental process and type and extent of involvement. Patients should be followed up closely with EEG.

The Burden of Primary Caregivers of Spinal Muscular Atrophy Patients and Their Needs.

AIM: This study aims to reveal the problems faced by families of children with spinal muscular atrophy (SMA), by evaluating their care burden, needs, and expectations. MATERIALS AND METHODS: The participants were the primary caregivers of 34 children between the ages of 0 and 18 years diagnosed with SMA. Thirteen children were diagnosed with type 1, 13 children with type 2 and 8 children with type 3 SMA. Data on the medical history, functional levels of the participants, and the characteristics of families were collected. The childrens' parents completed the Family Needs Survey and the Zarit Caregiver Burden Scale. RESULTS: According to the results of the Family Needs Survey, it was found that information was the most common requirement, and this was independent of the level of education. According to the Caregiver Burden Scale, it was recorded that 64.7% of the caregivers were under mild/moderate burden. While there was a moderate correlation (r = 0.574; P < .001) between the Caregiver Burden Scale and the Family Needs Survey, it was observed that the functional level of the child was not associated with family needs and caregiver burden. CONCLUSIONS: Our study suggests that the needs of families of SMA patients, especially related to income level, have changed. The caregivers' burden is not directly related to the income level or the functional level of the child. Families' need for information should also be prioritized within the rehabilitation program.

Acute flaccid myelitis outbreak through 2016-2018: A multicenter experience from Turkey.

AIM: We aim to describe the demographic characteristics, etiology, neurophysiology, imaging findings, treatment, prognosis, and prognostic factors of acute flaccid myelitis. METHODS: The clinical data, laboratory test and, magnetic resonance imaging (MRI) results of pediatric patients diagnosed with acute flaccid myelitis according to the Centers for Disease Control criteria between August 1, 2016, and December 31, 2018, from 13 centers in Turkey were reviewed. RESULTS: Of the 34 cases identified, 31 were confirmed (91.2%). Eighteen patients (55.9%) were boys. The median patient age was 4 years (interquartile range 2.5-6.9 years). Most of the patients were admitted in 2018 (n = 27). A preceding history of a febrile illness was reported in all patients, with a median of 4 days (interquartile range 3-7 days) before symptom onset. Thirty-one patients had T2 hyperintensity on spinal MRI, and 18 patients had cerebrospinal fluid pleocytosis. The most common infectious agents were entero/rhinoviruses (n = 5) in respiratory specimens. All patients except one received immunotherapy either alone or in combination. Among 27 patients with follow-up data 24 had persistent weakness. Involvement of four limbs together with an abnormal brain MRI at onset were associated with a poor prognosis. CONCLUSION: The number of patients with acute flaccid myelitis increased since 2012, spiking with every 2-year interval, largely in the pediatric population. The median age decreases with every outbreak. Clinicians should be aware of the clinical picture for early collection of specimens and early start of rehabilitation programs. Further studies are needed to better characterize the etiology, pathogenesis, risk factors, and treatment of this rare condition.

A comparison of the Mediterranean diet and current food consumption patterns in Spain from a nutritional and water perspective.

The promotion of responsible consumption is a key strategy to achieve environmental benefits, sustainable food security, and enhance public health. Countries like Spain are making efforts to reverse growing obesity and promote healthy diets, such as the recommended and traditional Mediterranean, recognized as a key strategy to improve the population's health with locally grown, traditional, and seasonal products like fruits, vegetables, olive oil, and fish. With a view to connecting water, agriculture, food security, nutrition and health, this research aims to investigate and compare the nutritional and water implications of the current food consumption of Spanish households with the recommended Mediterranean diet. Besides, we calculate their nutritional composition, compare their water footprints, and develop a new methodological approach to assess nutritional water productivity (i.e. the nutritional value per unit of embedded water). Results show that the current Spanish diet is shifting away from the recommended Mediterranean towards an alternative one containing three times more meat, dairy and sugar products, and a third fewer fruits, vegetables, and cereals. The Mediterranean diet is also less caloric, as it contains smaller amounts of proteins and fats and is richer in fiber and micronutrients. Due to the high-embedded water content in animal products, a shift towards a Mediterranean diet would reduce the consumptive WF about 750 l/capita day. Additionally, the Mediterranean diet has better water-nutritional efficiency than the current one: it provides more energy, fiber, and nutrients per liter of consumptive water. The study confirms the Mediterranean diet is a healthier and more sustainable diet with strong cultural heritage.