Gian Pietro Sechi

Humoral cross reactivity between α-synuclein and herpes simplex-1 epitope in Parkinson's disease, a triggering role in the disease?

Environmental factors are implicated in the development of Parkinsons disease (PD). We have investigated on the role of molecular mimicry between HSV1 and α-synuclein that could foster the progression of PD. The antibody response against homologous peptides in PD patients and healthy controls was evaluated, showing that these antibodies are highly prevalent among PD patients to healthy controls. The competitive assay demonstrated cross-reactivity between HSV1 and human α-synuclein peptides. The results may suggest the hypothesis of the involvement of HSV1 in stimulating the immune cells against the neurons of the substantia nigra as a consequence of the cross reactivity.

Valproate-induced parkinsonism, glial cells and Alexander's disease

A 39-year-old, right-handed woman was admitted in October 2005, because of progressive bladder dysfunction since age 35, the appearance of a restless legs syndrome at age 38 treated with pramipexole and a progressive blurred speech in the last five months. Family history was negative for neurological pathologies. Neurological examination showed no cognitive impairment, a severely dysarthric speech, hyperactive tendon reflexes, a mild gait ataxia and a rhythmic palatal myoclonus at 1.5-2 Hz. Physical examination, electrocardiogram, electroencephalogram, peripheral blood and cerebrospinal fluid parameters were all normal. T2 weighted and FLAIR brain Magnetic Resonance Imaging (MRI) revealed bilateral, highsignal-intensity areas posteriorly in the periventricular white matter, descending pyramidal tracts of the medulla and deep cerebellar white matter (Fig. 1). Patients DNA direct sequencing revealed two point mutations in the heterozygous form in the glial fibrillary acidic protein gene (GFAP), respectively in exon 1 and exon 2. In exon 1, a G to A substitution at nucleotide 209 was shown, resulting in change of arginine to glutamine at position 70 (R70Q), in exon 2, instead, a G to A substitution at nucleotide 469, resulting in change of aspartic acid to asparagine at position 157 (D157N) (Caroli et al., 2007; Li et al., 2006). Valproate administration at increasing doses, until 500mg twice daily, for the palatal myoclonus, led within 3 months to bradykinesia and rigidity. Neurological examination according to the Unified Parkinsons Disease Rating Scale (UPDRS) revealed the following motor scores: facial expression 2; speech 1; body bradykinesia 3; rigidity neck 2, right arm 2, left arm 2, right leg 2, left leg 2; finger taps right 1, left 2; leg agility right 2, left 2; arise from chair 1; posture 1; gait 1; postural stability 1 (total UPDRS motor score=27), corresponding to stage 2.5 of the Hoehn/Yahr Parkinsons Disease Scale. There was no cognitive impairment (Mini Mental State Examination score of 30). Blood valproate levels (EMIT system) ranged between 43-51 μg/mL (range values: 40-100 μg/mL). Valproate was ineffective on palatal myoclonus. Repeated laboratory findings were within normal limits. After valproate discontinuation, the parkinsonism cleared within one month (UPDRS motor score=0). No relapses of parkinsonian symptoms were observed in the 16 months following the valproate withdrawal. 3. Discussion

Distribution of diphenylhydantoin in the brain during experimental status epilepticus of the cat

The distribution of diphenylhydantoin (PHT) (40 mg/kg i.p.) in the brain was investigated in cats with convulsive generalized (group 1) and focal penicillin-induced status epilepticus (group 2), and in controls. A significant increase in the amount of PHT entering the brain during the convulsive status was found, with peak brain levels at 45 min (12 +/- 3.2 micrograms/g vs. 6.0 +/- 0.8 in normal cats, P less than 0.05). In the focal status brain concentrations of PHT reached levels intermediate between controls and group 1 cats. At 15 min, elevated blood levels of the drug were paralleled by increased concentrations in the brain, whereas at 30 and 45 min other factors, such as changes in cerebral blood flow, cerebral pH, vascular resistance, metabolic derangement and blood-brain barrier disruption were presumably responsible for the altered brain PHT uptake. The relevance of these data to clinical practice is discussed, in relation to the treatment of human status epilepticus and the potentially neurotoxic effects of the drug.

Acquired Ocular-Motor Apraxia and Right-Sided Cortical Angioma

A case of acquired ocular-motor apraxia featured by failure in voluntary initiation of lid closure, horizontal and vertical eye movements is reported. Electrographic and neuropsychological assessment pointed out several signs referable to bilateral frontal and right parietal lobe involvement, confirmed by neuroradiological finding.

“Acquired” hepatocerebral degeneration in a patient heterozygote carrier for a novel mutation in ATP7B gene

Acquired hepatocerebral degeneration (AHD) is a rare type of hepatic encephalopathy characterized by neuropsychiatric symptomatology, and peculiar neuroradiologic findings, without the clinical evidence of Wilson’s disease (WD). We studied a patient with AHD responsive to penicillamine who was heterozygote carrier for a novel mutation in the ATP7B gene, and discussed the possible role of the mutation in facilitating the appearance of the syndrome. A 37-year-old man with liver cirrhosis related to chronic hepatitis C was admitted because of progressive consciousness impairment. Family history was negative for WD. Ammoniemia was 176 lmol/L (NR, 9–33 lmol/L); total bilirubin 1.71 mg/dL (NR, 0.2–1.3 mg/dL); serum albumin 2.6 g/dL (NR, 3.3–5 g/dL); AST 62 U/L (NR, 10–45 U/L). Electroencephalogram disclosed diffuse slow wave activity. After rifaximin, lactulose, and branched chain amino acid infusion, his arousal state went back normal in about 12 hours, and ammonia levels decreased to 94 lmol/L.

Antibody response against HERV-W env surface peptides differentiates multiple sclerosis and neuromyelitis optica spectrum disorder

Background A specific humoral immune response against HERV-W envelope surface (env-su) glycoprotein antigens has been reported in serum of patients with multiple sclerosis (MS). However, it has not been evaluated to date in patients with neuromyelitis optica spectrum disorder (NMOSD). Objective The objective of this paper is to investigate whether antibody (Ab) response against HERV-W env-su antigenic peptides differs between NMOSD and MS. Methods Serum samples were collected from 36 patients with NMOSD, 36 patients with MS and 36 healthy control individuals (HCs). An indirect ELISA was set up to detect specific Abs against HERV-W env-su peptides. Results Our data showed that two antigenic peptides, particularly HERV-Wenv93–108 and HERV-Wenv248–262, were statistically significantly present only in serum of MS compared to NMOSD and HCs. Thus, the specific humoral immune response against HERV-W env-su glycoprotein antigens found in MS is widely missing in NMOSD. Conclusion Increased circulating serum levels of these HERV-W Abs may be suitable as additional biomarkers to better differentiate MS from NMOSD.

Differential expression of miRNA 155 and miRNA 146a in Parkinson's disease patients

Parkinsons disease is a neurodegenerative disorder and its etiology is unknown, numerous studies show how different environmental factors can influence the development of disease. miRNAs are involved in several pathologies and their dysregulation contribute to different pathologies, also in neurodegenerative such as Parkinsons disease, Alzheimers disease, Huntingtons disease and Amyotrophic lateral sclerosis. In this study, we profiled the expression of different candidate miRNAs: miR-155, miR-26a, miR-146a, and miR132, in PBMCs of L-dopa treated Parkinson patients and unaffected controls (HCs).We investigated the expression of miRNAs by RT-real time PCR, the results were subjected to statistical analysis. miRNA-155-5p was generally up-regulated in PD patients compared to HCs whereas miRNA-146a-5p was down-regulated in PD patients in comparison to HCs. It is interesting to point out that the expression of miR-155-5p was modified by levodopa treatment, in fact a down-regulation of miR-155-5p in PD patients with the highest dosage was observed. In conclusion, miRNA 155 could not only be a promising target for the anti-inflammatory therapy in PD but also a good candidate as a disease progression biomarker. The role of levodopa in modulating the levels of miRNA 155 requires further studies.