Serum Neurofilaments are a reliable biomarker to early detect PML in Multiple Sclerosis patients.

BACKGROUND: The earliest detection of progressive multifocal leukoencephalopathy (PML) is crucial in Natalizumab (NTZ)-treated Multiple Sclerosis (MS) patients. This study aims to assess serum Neurofilaments (sNFL) ability to early detect PML in longitudinal patients' follow-up. METHODS: NFL were retrospectively measured in four PML cases occurred at the Regional Referring Center for MS (CRESM, Italy), in samples collected since one year before PML diagnosis, at PML diagnosis, during PML and in post-PML follow-up. sNFL levels were interpreted according to previously defined reference values. Clinical examination and EDSS were performed at each NTZ infusion. Routinary MRI was undertaken every six months; after PML diagnosis, MRI was performed according to clinical evaluation. sNFL were also measured in 45 NTZ-treated patients experiencing NEDA-3 status for at least 12 months. RESULTS: Patients showed different PML onsets and manifestations: in 3 patients routinary brain MRI revealed radiological signs of PML preceding different clinical manifestations, while in one patient brain MRI was performed after the clinical onset. PML diagnosis was defined at the time of the first detection of JCV DNA in cerebrospinal fluid. The following different PML phases were considered: 1. Basal (up to 4 months before PML diagnosis): sNFL values were in the normal range in all patients' samples, except for one (median 9.1 pg/ml, range 6.2-15.1 pg/ml) 2. Pre-PML (within 3 months before PML diagnosis): sNFL were elevated in all available samples (median 19.50 pg/ml, range 15.50-33.80 pg/ml). 3. PML diagnosis: sNFL were elevated in all patients (median 59.20 pg/ml, range 11.1-101.50 pg/ml). 4. PML/IRIS: during this phase, sNFL levels reached their peak (median 96.35 pg/ml, range 20.5-272.9) in all patients. 5. Post-PML (recovery phase, starting from the first MRI without enhancement, up to the end of follow-up): sNFL levels showed a decrease (median 12.80 pg/ml, range 9.30-30.60); however, based on reference values, sNFL were still elevated in 2 out of 4 patients at the end of their follow-up (622 and 887 days after PML diagnosis). sNFL were always elevated when MRI scan suggested a suspicious of PML. In NEDA-3 patients, sNFL levels were in the normal range in all patients' samples (median 4.7 pg/ml, range 1.4-8.6 pg/ml). CONCLUSION: Elevated sNFL were observed not only at PML diagnosis, but also in pre-PML phase. At PML recovery, sNFL weren't normalized in all patients' samples, suggesting ongoing neuronal degeneration. sNFL represent a reliable biomarker and should be introduced in clinical practice as an additional/alternative parameter to MRI to early detect and monitor PML.

No impact of current therapeutic strategies on disease reactivation after natalizumab discontinuation: a comparative analysis of different approaches during the first year of natalizumab discontinuation.

BACKGROUND AND PURPOSE: Natalizumab discontinuation induces the recurrence of multiple sclerosis disease activity: currently no therapeutic approach has been found able to abolish disease reactivation. METHODS: The recurrence of disease activity after natalizumab discontinuation was retrospectively evaluated in 79 patients who had been treated with immunomodulating agents, other first-line therapies, fingolimod or not treated. RESULTS: No differences have been found in clinical or magnetic resonance imaging recurrence of disease activity amongst the groups. Interestingly, no disease reactivation was observed only in one patient treated for 6 months with monthly pulses of cyclophosphamide. CONCLUSION: Disease modifying treatment or 'no treatment' is unable to abolish disease activity reactivation after natalizumab discontinuation.

Recommendations for the management of urinary disorders in multiple sclerosis: a consensus of the Italian Multiple Sclerosis Study Group.

Urinary disorders are uncommon in the initial phases of multiple sclerosis, but increase in frequency as the disease progresses, with a negative impact on quality of life. The goal of this study was to propose a protocol for the diagnosis and treatment of urinary disorders in multiple sclerosis, based on data from the scientific literature and the experience of Italian clinical centres. In particular, the following clinical aspects were considered: what to do with patients with asymptomatic multiple sclerosis; what to do with symptomatic patients; how and when to perform a second-level diagnostic evaluation; and how to treat urinary disorders. A diagnostic-therapeutic algorithm is proposed, that can be applied in Italian clinical centres.

Psychiatric comorbidity in patients evaluated for chronic epilepsy: a differential role of the right hemisphere?

INTRODUCTION: Psychiatric disorders are known to occur frequently in chronic epilepsy. The aim of this study is to investigate the prevalence of psychiatric comorbidity and its relationship to regional cerebral dysfunction in patients admitted to a tertiary epilepsy center for epilepsy surgery. METHODS: 217 patients were investigated. A presurgical workup was performed and allowed precise localization of the epileptogenic focus in 156 patients. Sixty-one patients had multifocal or generalized discharges. After 1-3 psychiatric interviews, a psychiatric diagnosis was made (DSM-IV classification). RESULTS: Psychiatric comorbidity was found in 85 patients (39%), more often in those with right or bilateral hemispheric dysfunction (74%, p = 0.04) with no difference between temporal or extratemporal foci location frequency. Additionally, patients with psychiatric disorders were less likely to undergo epilepsy surgery compared to 'epilepsy-only' patients (p = 0.003), despite similar good outcome in patients with and without psychiatric comorbidity. CONCLUSIONS: Right-sided or bilateral foci seem to represent a risk factor for psychiatric comorbidity in epilepsy, although we did not find any particular association between a psychiatric syndrome and focus localization. Recognition and treatment of psychiatric comorbidity is of major importance since its presence may interfere with patient's decision making for epilepsy surgery treatment.

ICTAL aphasia as manifestation of partial status epilepticus in a long-lasting misdiagnosed symptomatic epilepsy: an emblematic case.

Magnetic Resonance Imaging (MRI) represents the procedure of choice for detection of anatomical lesions in epilepsy. Vascular malformations in central nervous system, such as cavernoma, can cause symptomatic epilepsy. We describe a case of ictal aphasia as manifestation of a partial status epilepticus probably due to a mutual interaction between a recent bleeding cavernoma and a concomitant reduction of antiepileptic treatment in a long-lasting misdiagnosed symptomatic epilepsy. We conclude that MRI is a mandatory diagnostic method to identify structural abnormalities underlying epilepsy in all patients affected by recurrent focal seizures independent of the duration of epilepsy.

Sleep episodes and daytime somnolence as result of individual susceptibility to different dopaminergic drugs in a PD patient: a polysomnographic study.

The association between excessive daytime somnolence (EDS) and idiopathic Parkinson's disease (PD) is often reported but still debated. The possible role of antiparkinsonian therapy or primarily of PD on excessive diurnal sleepiness is controversial. We describe the case of a 61-year-old patient affected by PD who experienced sleep episodes (SE) occurring during pramipexole plus L-Dopa therapy. Polysomnographic sleep studies and subjective evaluations of daytime sleepiness (Epworth Sleepiness Scale) were carried out under administration of pramipexole plus L-Dopa, L-Dopa monotherapy and cabergoline plus L-Dopa. The polysomnography revealed two sleep events during pramipexole plus L-Dopa. Moreover, the polysomnographic data showed an increase of both diurnal and nocturnal sleep under pramipexole plus L-Dopa compared with cabergoline plus L-Dopa and L-Dopa as monotherapy. In addition, while Epworth Sleepiness Scale (ESS) Score showed a mild sleepiness under pramipexole (ESS score=11), ESS scores were normal under both L-Dopa and cabergoline plus L-Dopa. Sleep episodes also disappeared under both L-Dopa and cabergoline plus L-Dopa (2- and 12-month follow-up). We hypothesize that an individual susceptibility to specific antiparkinsonian drug may play a significant role in the genesis of sleepiness in our PD patient.

Bilateral frontal polymicrogyria and epilepsy in a patient with Turner mosaicism: a case report.

Turner's syndrome (TS) is rarely associated with serious abnormalities of brain structure or malformations of cortical development. We report a 17-year-old girl with TS and 45,XO/46,XX mosaicism presenting bilateral frontal polymicrogyria (BFP) and epilepsy. To our knowledge, the association between TS and BFP has never been reported to date. Our observation confirms that in humans the X-chromosome plays an important role in the development and specialization of brain structure and function. We hypothesize that the absence or abnormalities of developmental genes localized on the X-chromosome could be involved in the pathogenesis of BFP observed in our patient.

Cortical dysplasia, temporal atrophy, mental retardation, dysmorphic facies, and partial epilepsy: an EEG and dynamic susceptibility contrast (DSC) MRI study in a new possible genetic syndrome.

We report the case of a 24-year-old female with partial epilepsy, mental retardation, and dysmorphic facies. In EEG, a high spiking rate (HSR) was evident with abnormalities in the right frontal region. Morphological MRI showed a left temporo-mesial sclerosis and a cortical dysplasia localized in the right frontal cortex. Dynamic susceptibility contrast (DSC) MRI showed hyperperfusion in right frontal region and hypoperfusion in left fronto-temporal region. Left fronto-temporal hypoperfusion is consistent with temporo-mesial sclerosis. Right frontal hyperperfusion is related to the cortical dysplasia area with HSR. HSR may resemble both electroencephalographic and perfusional ictal pattern. DSC MRI is useful in the evaluation of regions involved in the genesis of ictal and interictal epileptiform activity. Furthermore, we hypothesize that our patient would be affected by a new possible genetic syndrome.

Ketotic hyperglycemia and epilepsia partialis continua.

Epilepsia partialis continua (EPC) may occur during nonketotic hyperglycemia but has not been described with diabetic ketoacidosis. The authors report a patient with EPC associated with ketotic hyperglycemia. Brain MRI showed two areas of abnormal signal intensity in the left precentral gyrus and in the right cerebellar hemisphere. Hyperglycemia may reduce seizure threshold because of the increase in gamma-aminobutyric acid metabolism and may trigger epileptic discharges.