Late adult-onset adrenomyeloneuropathy evolving with atypical severe frontal lobe syndrome: Importance of neuroimaging.

X-linked adrenoleukodystrophy (X-ALD) is a rare inherited metabolic disease affecting the nervous system and the adrenal glands. It is caused by a mutation of the ABCD1 gene, resulting in the impaired degradation of very long-chain fatty acids and their subsequent accumulation in several organs and tissues. X-ALD is notable for its high phenotypical variability, that includes isolated adrenocortical insufficiency, slowly progressive myelopathy with paraparesis, ataxia, and peripheral neuropathy to severe childhood cerebral forms. Here, we describe the case of an X-ALD patient with a p.Gly343Val mutation in ABCD1 gene, who presented in adulthood with a spinal syndrome of mild severity, and later developed a progressive cognitive and behavioral syndrome. Our patient showed a striking correlation between clinical phenotype and neuroimaging, including a brain fluoro-2-deoxy-d-glucose positron emission tomography that displayed an atypical cerebral glucose metabolism.

Synergistic Interplay between Curcumin and Polyphenol-Rich Foods in the Mediterranean Diet: Therapeutic Prospects for Neurofibromatosis 1 Patients.

Neurofibromas are the hallmark lesions in Neurofibromatosis 1 (NF1); these tumors are classified as cutaneous, subcutaneous and plexiform. In contrast to cutaneous and subcutaneous neurofibromas, plexiform neurofibromas can grow quickly and progress to malignancy. Curcumin, a turmeric-derived polyphenol, has been shown to interact with several molecular targets implicated in carcinogenesis. Here, we describe the impact of different dietary patterns, namely Mediterranean diet (MedDiet) compared to the Western diet (WesDiet), both with or without curcumin, on NF1 patients' health. After six months, patients adopting a traditional MedDiet enriched with 1200 mg curcumin per day (MedDietCurcumin) presented a significant reduction in the number and volume of cutaneous neurofibromas; these results were confirmed in subsequent evaluations. Notably, in one patient, a large cranial plexiform neurofibroma exhibited a reduction in volume (28%) confirmed by Magnetic Resonance Imaging. Conversely, neither unenriched MedDiet nor WesDiet enriched with curcumin exhibited any significant positive effect. We hypothesize that the combination of a polyphenol-rich Mediterranean diet and curcumin was responsible for the beneficial effect observed on NF1. This is, to the best of our knowledge, the first experience with curcumin supplementation in NF1 patients. Our report suggests that an integrated nutritional approach may effectively aid in the management of NF1.

Rasagiline for sleep disorders in patients with Parkinson's disease: a prospective observational study.

INTRODUCTION: Rasagiline is a selective, irreversible monoamine oxidase B inhibitor that ameliorates the symptoms of Parkinson's disease (PD) by inhibiting striatal dopamine metabolism. There is also evidence that monoamine oxidase B inhibitors increase melatonin levels in the pineal gland and may have a beneficial effect on sleep disorders, which are a common feature in patients with PD. METHODS: This single-center, prospective, observational, 12-week study compared the effect of combination therapy with levodopa 200-300 mg/d + rasagiline 1 mg/d (n=19) with levodopa 200-300 mg/d alone (n=19) in the treatment of sleep disorders in patients with idiopathic PD. RESULTS: After 12 weeks' treatment, mean sleep latency was significantly (P<0.001) lower and the improvement in sleep latency from baseline was significantly (P=0.001) greater in patients receiving levodopa + rasagiline than in patients receiving levodopa alone. Similarly, at the end of the study, the mean total sleep time was significantly (P=0.002) longer and the improvement from baseline in mean total sleep time was significantly (P=0.026) greater in patients receiving levodopa + rasagiline than levodopa alone. There were no significant differences between treatment groups for the mean number of awakenings reported at week 12 nor the change from baseline to week 12 in mean number of awakenings. CONCLUSION: Adding rasagiline to levodopa improved sleep outcomes and may be an appropriate option for patients with PD experiencing sleep disorders.

A novel diagnostic method to detect truncated neurofibromin in neurofibromatosis 1.

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic condition caused by dominant loss-of-function mutations of the tumor suppressor gene NF1 that encodes neurofibromin, a negative regulator of RAS activity. Mutation analysis of NF1 located at 17q11.2 has been hampered by the large size of the gene, the high rate of new mutations, the lack of mutational clustering, and the presence of several homologous loci. To date, about 80% of the reported NF1 mutations are predicted to result in protein truncation, but very few studies have correlated the causative NF1 mutation with its effect at the protein level. We evaluated a novel diagnostic method to detect truncated forms of neurofibromin in a large cohort of unrelated subjects suspected of having NF1, according to the NIH consensus criteria. Western blot analysis was carried out on protein extracts from patients' leukocytes to highlight the possible presence of altered neurofibromin as a result of mutations in NF1. Truncated neurofibromin was identified in 274/336 patients (81%), confirming the usefulness and reproducibility of the proposed diagnostic approach. Our methodology can be routinely applied in the diagnostic setting, thanks to its simplicity and reliability. Combined with molecular approaches, it may increase the accuracy and efficiency of NF1 genetic testing. We evaluated a novel diagnostic method to detect truncated forms of neurofibromin in patients fulfilling the clinical criteria for Neurofibromatosis 1. Western blot analysis identified truncated neurofibromin in 274/336 patients (81%). Our results indicate that the proposed technique is cheap and reliable, and could ideally be performed as a preliminary biochemical screening before molecular analysis of the NF1 gene.

Foix-Chavany-Marie syndrome in a 17-year-old female with congenital cytomegalovirus infection.

Foix-Chavany-Marie syndrome is characterized by bilateral facio-glosso-pharyngo-masticatory paralysis of voluntary movement due to bilateral anterior opercular lesions. We describe the case of a 17-year-old female affected by Foix-Chavany-Marie syndrome and congenital cytomegalovirus infection, evaluating the possible etiopathogenetic correlation between cerebral cortical dysplasia and intrauterine infections.

Giant thrombosed intracavernous carotid artery aneurysm presenting as Tolosa-Hunt syndrome in a patient harboring a new pathogenic neurofibromatosis type 1 mutation: a case report and review of the literature.

Neurofibromatosis type 1 (NF1) is a relatively common single-gene disorder, and is caused by heterozygous mutations in the NF1 gene that result in a loss of activity or in a nonfunctional neurofibromin protein. Despite the common association of NF1 with neurocutaneous features, its pathology can extend to numerous tissues not derived from the neural crest. Among the rare cerebrovascular abnormalities in NF1, more than 85% of cases are of purely occlusive or stenotic nature, with intracranial aneurysm being uncommon. Predominantly, the aneurysms are located in the internal carotid arteries (ICAs), being very rare bilateral aneurysms. This report describes a very unusual case of fusiform aneurysms of both ICAs in a Caucasian NF1 patient, with a new pathogenic intragenic heterozygous deletion of the NF1 gene, presenting at age 22 years with Tolosa-Hunt syndrome, because of partial thrombosis of the left giant intracavernous aneurysm. Medical treatment with anticoagulant therapy allowed a good outcome for the patient. In conclusion, early identification of cerebral arteriopathy in NF1 and close follow-up of its progression by neuroimaging may lead to early medical or surgical intervention and prevention of significant neurologic complications.