on Journal of the neurological sciences
by Signoriello E, Cirillo M, Puoti G, Signoriello G, Negro A, Koci E, Melone MAB, Rapacciuolo A, Maresca G, Lus G
To investigate a possible association between isolated white matter lesions suggestive of demyelinating disease in magnetic resonance imaging (MRI) and patent foramen ovale (PFO) evidence in migraine patients, with or without aura.
on Neurobiology of aging
by Coppola C, Saracino D, Puoti G, Lus G, Dato C, Le Ber I, Pariente J, Caroppo P, Piccoli E, Tagliavini F, Di Iorio G, Rossi G
Frontotemporal lobar degeneration (FTLD) is a group of neurodegenerative diseases displaying high clinical, pathologic, and genetic heterogeneity. Several autosomal dominant progranulin (GRN) mutations have been reported, accounting for 5%-10% of FTLD cases worldwide. In this study, we described the clinical characteristics of 7 Italian patients, 5 with a diagnosis of frontotemporal dementia behavioral variant and 2 of corticobasal syndrome (CBS), carrying the GRN deletion g.101349_101355delCTGCTGT, resulting in the C157KfsX97 null mutation, and hypothesized the existence of a founder effect by means of haplotype sharing analysis. We performed plasma progranulin dosage, GRN gene sequencing, and haplotype sharing study, analyzing 10 short tandem repeat markers, spanning a region of 11.08 Mb flanking GRN on chromosome 17q21. We observed shared alleles among 6 patients for 8 consecutive short tandem repeat markers spanning a 7.29 Mb region. Therefore, also with this particular mutation, the elevated clinical variability described among GRN-mutated FTLD cases is confirmed. Moreover, this is the first study reporting the likely existence of a founder effect for C157KfsX97 mutation in Southern Italy.
on Neurosurgical focus
by Bonda DJ, Manjila S, Mehndiratta P, Khan F, Miller BR, Onwuzulike K, Puoti G, Cohen ML, Schonberger LB, Cali I
The human prion diseases, or transmissible spongiform encephalopathies, have captivated our imaginations since their discovery in the Fore linguistic group in Papua New Guinea in the 1950s. The mysterious and poorly understood "infectious protein" has become somewhat of a household name in many regions across the globe. From bovine spongiform encephalopathy (BSE), commonly identified as mad cow disease, to endocannibalism, media outlets have capitalized on these devastatingly fatal neurological conditions. Interestingly, since their discovery, there have been more than 492 incidents of iatrogenic transmission of prion diseases, largely resulting from prion-contaminated growth hormone and dura mater grafts. Although fewer than 9 cases of probable iatrogenic neurosurgical cases of Creutzfeldt-Jakob disease (CJD) have been reported worldwide, the likelihood of some missed cases and the potential for prion transmission by neurosurgery create considerable concern. Laboratory studies indicate that standard decontamination and sterilization procedures may be insufficient to completely remove infectivity from prion-contaminated instruments. In this unfortunate event, the instruments may transmit the prion disease to others. Much caution therefore should be taken in the absence of strong evidence against the presence of a prion disease in a neurosurgical patient. While the Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) have devised risk assessment and decontamination protocols for the prevention of iatrogenic transmission of the prion diseases, incidents of possible exposure to prions have unfortunately occurred in the United States. In this article, the authors outline the historical discoveries that led from kuru to the identification and isolation of the pathological prion proteins in addition to providing a brief description of human prion diseases and iatrogenic forms of CJD, a brief history of prion disease nosocomial transmission, and a summary of the CDC and WHO guidelines for prevention of prion disease transmission and decontamination of prion-contaminated neurosurgical instruments.
on The International journal of neuroscience
by Imbriani P, Marfia GA, Marciani MG, Poleggi A, Pocchiari M, Puoti G, Caltagirone C, Pisani A
To report two members of the same family carrying the valine to isoleucine point mutation of the prion protein gene (PRNP) and presenting with visual symptoms as initial manifestation as in the "Heidenhain variant" of sporadic Creutzfeldt-Jakob disease (CJD).
on Alzheimer disease and associated disorders
by Ghoshal N, Perry A, McKeel D, Schmidt RE, Carter D, Norton J, Zou WQ, Xiao X, Puoti G, Notari S, Gambetti P, Morris JC, Cairns NJ
on Puerto Rico health sciences journal
by Del Pilar-Morales EA, Cali I, Chapas J, Bertrán-Pasarell J, Puoti G, Gambetti P, Nobo U
The diagnosis of Creutzfeldt-Jakob disease (CJD) is often a challenge for most physicians given its extremely low incidence and different clinico-pathological presentations. We report the case of a 56-year old patient native to Puerto Rico suspected of sporadic Creutzfeldt-Jakob disease (sCD). The symptoms at onset were notorious for bilateral cortical blindness followed by rapidly progressive cognitive decline, visual deficit, increased levels of CSF 14-3-3 and tau along with positive brain MRI and EEG, are highly indicative of CJD. The definite diagnosis was confirmed by the National Prion Disease Pathology Surveillance Center (NPDPSC), in Cleveland, Ohio, USA. Lack of genetic mutations in the prion protein (PrP) gene, widespread histopathological changes and the accumulation of scrapie PrP (PrPSc) in the brain confirmed the diagnosis of sCJD. The patient, admitted to our institution in 2011, represents the first detailed report of sCJD in a native Puerto Rican patient living in Puerto Rico.
by Xiao X, Cali I, Yuan J, Cracco L, Curtiss P, Zeng L, Abouelsaad M, Gazgalis D, Wang GX, Kong Q, Fujioka H, Puoti G, Zou WQ
In transmission studies with Alzheimer's disease (AD) animal models, the formation of Aβ plaques is proposed to be initiated by seeding the inoculated amyloid β (Aβ) peptides in the brain. Like the misfolded scrapie prion protein (PrPSc) in prion diseases, Aβ in AD shows a certain degree of resistance to protease digestion while the biochemical basis for protease resistance of Aβ remains poorly understood. Using in vitro assays, histoblotting, and electron microscopy, we characterize the biochemical and morphological features of synthetic Aβ peptides and Aβ isolated from AD brain tissues. Consistent with previous observations, monomeric and oligomeric Aβ species extracted from AD brains are insoluble in detergent buffers and resistant to digestions with proteinase K (PK). Histoblotting of AD brain tissue sections exhibits an increased Aβ immunoreactivity after digestion with PK. In contrast, synthetic Aβ40 and Aβ42 are soluble in detergent buffers and fully digested by PK. Electron microscopy of Aβ40 and Aβ42 synthetic peptides shows that both species of Aβ form mature fibrils. Those generated from Aβ40 are longer but less numerous than those made of Aβ42. When spiked into human brain homogenates, both Aβ40 and Aβ42 acquire insolubility in detergent and resistance to PK. Our study favors the hypothesis that the human brain may contain cofactor(s) that confers the synthetic Aβ peptides PrPSc-like physicochemical properties.
on The neuroradiology journal
by Strianese D, Napoli M, Russo C, D'Errico A, Scotti N, Puoti G, Bonavolontà G, Tranfa F, Briganti F
Coexistence of orbital cavernous hemangioma and other vascular malformations is unusual and few cases have been reported. We describe the clinical and radiological features of three cases of orbital cavernous hemangiomas associated with other vascular malformations, selected reviewing a series of 181 cases of cavernous hemangiomas. All patients were males (age ranging from 43 to 67 years) without vascular systemic disorders and/or a clinical syndrome. They experienced slow progressive exophthalmos. One of them developed acute pulsatile proptosis (case 2), while another experienced slow progressive diplopia (case 3). In one case vascular lesions were bilateral (case 3) and in two patients two different lesions coexisted in the same orbit (cases 1 and 2). All patients underwent surgical excision, which was partial in two cases. Two patients had cavernous hemangiomas in association with a venous malformation (a varix in case 1 and a lymphangioma in case 2), while in the other ones (case 3) cavernous hemangioma was associated with a low-flow arteriovenous malformation. No patient denied visual impairment postoperatively. Few cases of orbital cavernous hemangiomas coexisting with other vascular malformations have been reported in the literature. This entity seems to be an association of different variants of orbital vascular malformations, presenting with a wide spectrum of clinical forms and probably with the same pathogenesis.
on Journal of Alzheimer's disease : JAD
by Puoti G, Lerza MC, Ferretti MG, Bugiani O, Tagliavini F, Rossi G
Frontotemporal lobar degeneration (FTLD) is a very heterogeneous disorder. It is genetically linked to three major genes: microtubule-associated protein tau (MAPT), progranulin (GRN), and C9ORF72. In particular, mutations in GRN account for 5-10% of all cases and give rise to a wide spectrum of clinical phenotypes, ranging from behavioral frontotemporal dementia (bvFTD) to primary progressive aphasia, including progressive non-fluent aphasia (PNFA) and semantic dementia, and corticobasal syndrome (CBS). We studied a family affected by FTLD whose members showed three different phenotypes: bvFTD, PNFA, and CBS. We performed plasma progranulin measurement before any genetic analyses and, due to the low level detected, we sequenced GRN and found the new mutation EX0-5' splice site A > G in the 5'-UTR region, where no pathogenic mutations had been previously demonstrated. Genetic analyses of MAPT and C9ORF72 were normal. GRN mRNA expression showed about 50% reduction caused by this mutation, and similar results were found for progranulin level. Testing of nonsense mediated RNA decay gave negative results, suggesting a different mechanism of mRNA degradation. In summary, the EX0-5' splice site A > G mutation widens the GRN regions affected by null mutations, including the 5'-UTR, and confirms once more the large phenotypic variability linked to GRN mutations.
on Case reports in neurology
by Puoti G, Elefante A, Saracino D, Capasso A, Cotrufo R, Anello CB
New-onset refractory status epilepticus (NORSE) is a recently defined clinical entity that describes patients who present with status epilepticus of unclear etiology that is highly refractory to therapy. Magnetic resonance imaging (MRI) of NORSE usually discloses no specific abnormalities except for an occasional mild T2/FLAIR hyperintense signal of the mesial temporal lobe. Here, we report a peculiar case of NORSE in which brain MRI showed massive alteration of both temporal lobes, with features strongly supporting the diagnosis of herpes virus encephalitis, but lacking any laboratory evidence of viral infection in the blood and cerebrospinal fluid. It showed also striking signal alterations in the thalamus, which got worse in the course of the disease. This report emphasizes the possibility that seizure activity alone plays a critical role in both determining the disease and whether it will be self-sustaining.