Neurological Sciences

Published by Springer Verlag
Online ISSN: 1590-3478
Publications
First-line medications for migraine prevention 
Article
Prophylactic treatment is mainly intended to reduce the frequency of migraine attacks, enhance response to acute medications, improve patient function and reduce disability. Sufficient evidence and consensus exist to recommend propranolol, timolol, amitriptyline, pizotifen, divalproex, sodium valproate and topiramate as first line agents for migraine prevention. These drugs can halve the frequency of attacks in 50% of patients. The anticipated benefit must be weighed against the adverse effects associated with each agent in determining the optimal preventive regimen for individual patients considering any comorbid conditions that are often present. The decision to treat and the choice of prophylactic drug must be taken with the patient. It is important to balance expectations and therapeutic realities for each particular drug. Recent data on the effect of prophylactic treatment on trigeminovascular activation and on cortical spreading depression emphasise the importance of developing research on migraine-preventive drugs.
 
Article
Class I clinical trials demonstrated that immunomodulatory treatments (interferon-beta and glatiramer acetate) reduce the disease activity and the accumulation of disability in relapsing-remitting multiple sclerosis (MS). Moreover, interferon-beta-1b had similar positive effects also in secondary progressive MS. The magnitude of these clinical effects was modest, but the reduction of inflammatory activity, as revealed by magnetic resonance imaging, was marked. There is converging evidence from new pathological studies and from new magnetic resonance techniques, characterised by an increased pathological specificity, that already in the early phases of the disease the inflammatory activity determines irreversible axonal damage. Moreover, the amount of inflammatory activity at clinical presentation of the disease has some value for predicting long-term disability. Taken together, these data indicate that patients may benefit from early treatment; the positive results of three double-blind placebo-controlled clinical trials (Early Treatment of Multiple Sclerosis and Controlled High Risk Subjects Avonex Multiple Sclerosis Prevention Study and BENEFIT) support this conclusion.
 
Article
Access to effective acute stroke services is a crucial factor to reduce stroke-related death and disability, but is limited in different parts of Italy. Our study addresses this inequality across the Italian regions by examining the regional legislations issued to adopt and implement the State-Regional Council agreement 03/02/2005 as to the acute stroke management. All decrees and resolutions as to acute stroke were collected from each region and examined by the means of a check list including quantitative and qualitative characteristics, selected in accordance with the recommendations from the State-Regional Council document. Each completed check list was then sent to each regional reference person, who filled in the section on the implementation of the indications and compliance, with the collaboration of stroke specialists if necessary. The study was carried out from November 2009 to September 2010. The documents and information were collected from 19 regions. Our survey revealed disparities both in terms of number of decrees and resolutions and of topics covered by the regional legislations about stroke care. Most legislations lacked practical and economical details. This feedback from national and regional stroke regulations revealed a need of more concrete indications. Involvement of various stakeholders (legislators, consumers, providers) might possibly ensure that policies are actually adopted, implemented and maintained. Although considerable challenges are present to the development of standard and optimal stroke care more widely across Italian regions, the potential gains from such developments are substantial.
 
Representative FSE (TR = 2,000 ms, ETE = 80 ms) images of control (No. 3) and TGN-020 treated mouse (No. 5). Note that midline shift due to ischemic brain swelling is much less conspicuous in the TGN-020 treated mouse 
Summary of physiological parameters and results 
Article
We investigated the in vivo effects of a novel aquaporin 4 (AQP4) inhibitor 2-(nicotinamide)-1,3,4-thiadiazole, TGN-020, in a mouse model of focal cerebral ischemia using 7.0-T magnetic resonance imaging (MRI). Pretreatment with TGN-020 significantly reduced brain edema associated with brain ischemia, as reflected by percentage of brain swelling volume (%BSV), 12.1 ± 6.3% in the treated group, compared to (20.8 ± 5.9%) in the control group (p < 0.05), and in the size of cortical infarction as reflected by the percentage of hemispheric lesion volume (%HLV), 20.0 ± 7.6% in the treated group, compared to 30.0 ± 9.1% in the control group (p < 0.05). The study indicated the potential pharmacological use of AQP4 inhibition in reducing brain edema associated with focal ischemia.
 
Article
We sought to investigate potential racial disparities in early outcomes of young individuals with stroke in an international multicenter study. We evaluated consecutive patients with first-ever acute stroke aged 18-45 years from prospective databases involving 12 tertiary-care stroke centers in North America (n = 2), Europe (n = 6), and Asia (n = 4). Demographics, vascular risk factors, stroke subtypes, pre-stroke functional status, stroke severity, blood pressure parameters, and serum glucose at hospital admission were documented. The outcome events of interest were 30-day mortality and 30-day favorable functional outcome (FFO) defined as modified-Rankin Scale score of 0-1. A total of 1,134 young adults (mean age 37.4 ± 7.0 years; 58.8 % men; 48.6 % Whites, 23.9 % Blacks, and 27.5 % Asians; median baseline National Institutes of Health Stroke Scale score 6 points, interquartile range 2-13) were included in the analyses. The 30-day stroke mortality and FFO rates differed (p < 0.001) across races. After adjusting for potential confounders, race was independently associated with 30-day mortality (p = 0.026) and 30-day FFO (p = 0.035). Blacks had a fourfold higher odds of 30-day stroke mortality in comparison to Asians (OR 4.00; 95 % CI 1.38-11.59; p = 0.011). Whites also had an increased likelihood of 30-day stroke mortality in comparison to Asians (OR 3.59; 95 % CI 1.28-10.03; p = 0.015). Blacks had a lower odds of 30-day FFO in comparison to Whites (OR 0.57; 95 % CI 0.35-0.91; p = 0.018). Racial disparities in early outcomes following first-ever stroke in young individuals appear to be independent of other known outcome predictor variables. Whites appear to have higher likelihood of 30-day FFO and Asians have lower odds of 30-day stroke mortality.
 
Article
Ischemic brain cell death is presumably caused by excitotoxicity. In addition to an increase of glutamate release during ischemia, the deficiency of astrocytic glutamate-reuptake may cause glutamate accumulation, which results in GABAergic neurons being vulnerable to ischemia. To confirm this hypothesis, we studied the pathophysiological changes of cortical astrocytes and GABAergic neurons during ischemia as well as the prevention of their injuries. Ischemia led to the sequential impairments of astrocytic glutamate-transporter currents and GABAergic neuronal excitability. The changes were partially reversed by 3,5-DHPG, an agonist of type-I/V metabotropic glutamate receptors (mGluR). Thus, mGluR(1,5) activation may be useful against the sequential impairment of cortical astrocytes and GABAergic neurons in an early stage of ischemia.
 
Article
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is commonly overlooked or misdiagnosed owing to its recent identification. It is characterized clinically by recurrent cerebral infarcts, usually appearing between the ages of 30 and 50 years, subcortical dementia, and pseudobulbar palsy. It begins with migraine with aura in approximately one-third of patients. The pathological hallmark of angiopathy is the presence of characteristic granular osmiophilic material (GOM) within the basal lamina of smooth muscle cells. The defective gene in CADASIL is Notch3, which encodes a large transmembrane receptor, and 70% of missense mutations are in exons 3 and 4. Each gene defect leads to either a gain or loss of a cysteine residue in the extracellular N-terminal domain of the molecule. We report the case of a 53-year-old woman admitted to the hospital for transient ischemic attack and stroke-like episodes recurrent since age 43 years. The patient had pseudobulbar palsy, pyramidal signs, and cognitive impairment but not frank dementia. Cerebral MRI showed periventricular diffuse and confluent ischemic lesions. Ultrastructural study revealed an abnormal deposition of granular osmiophilic material (GOM) within the basal lamina in skin capillaries. Direct sequence analysis of the Notch3 gene was performed. Since no mutation was detected in exons 3 and 4, the remaining exons were sequenced and a missense mutation, CGC-TGC in codon 1006 of exon 19 was found. The mutation led to a gain of a cysteine residue. This is the first missense mutation in codon 1006 of exon 19 of the Notch3 gene to be described in Italy and the second reported in the literature.
 
Scores on Italian standardised neuropsychological tests in the 6 genetically affected individuals 
Pedigrees of the two families. The roman numbers on the left represent the generation. The arabic numerals under each symbol identify the individuals in the relevant generation; * denotes the subjects who underwent genetic examination. A diagonal line through square (men) or circle (women) represents a deceased person. Filled symbols indicate subjects with mutation; half-filled symbols represent subjects who were considered affected on the basis of available medical or historical data; ? denotes subjects for whom insufficient clinical data were available
Article
Here we describe clinical, neuropsychological and neuroradiological findings in 6 subjects belonging to two unrelated Italian cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) kindreds from the same geographic area who shared a common Arg1006Cys mutation. Subjects from Family A were virtually asymptomatic, and yet showed MRI pathological findings and a cluster of sub-clinical neuropsychological defects mainly centred on the visuospatial domain; patients from Family B had presented several clinically relevant episodes and showed a general cognitive impairment compatible with the clinical picture of vascular dementia. The present clinical observations are consistent with the hypothesis of a geographical clustering for CADASIL, and highlight that sub-clinical cognitive impairment may help to identify this syndrome in families presenting with only migraine.
 
Clinical and genetic data of the patient with SCA21.: (A) Patient pedigree (Arrow points to affected patient); (B) Electropherogram of Sanger sequencing of PCR products from the members of the patient pedigree. From top to bottom: I:1 (father), I:2 (mother), II:2 (sister), II:3 (sister), II:4-F/II:4-R (proband, F and R represent forward and reverse sequencing, respectively). Red arrow indicates the mutation (c.509C > T). (C) Cranial magnetic resonance images: mild cerebellar atrophy was indicated.
Article
The spinocerebellar ataxias (SCAs) are a clinically and genetically heterogeneous group of neurodegenerative diseases. Researchers have recently found that SCA type 11 (SCA11) is associated with mutations in the TTBK2 gene. In our previous work, we performed mutation detection in SCA1, 2, 3, 6, 7, 8, 10, 12, 17 and dentatorubral-pallidoluysian atrophy gene in Chinese SCA patients, but the genes responsible for approximately 40% of our patients have not yet been identified. To investigate the frequency of SCA11 in Chinese SCA patients, we examined the TTBK2 gene in 68 unrelated probands diagnosed with dominantly inherited ataxia using the denaturing high-performance liquid chromatography method. All analyzed samples displayed the normal elution profile, which denoted that no disease-related mutation was identified. We provided the evidence that SCA11 is a rare form of ataxia in China.
 
Article
Neuroimaging studies of the striatal dopamine transporter (DAT) are useful in the assessment of the dopaminergic system in Parkinson's disease (PD). We used positron emisson tomography (PET) and the tracer [11C]FE-CIT to measure DAT binding in the caudate nucleus and putamen of 31 patients with PD, 5 with essential tremor and 8 healthy control subjects. Of the patients with PD, 17 were drug naive, while the others were either on levodopa or dopamine agonist monotherapy. DAT binding was significantly reduced in the caudate nucleus and to a greater extent in the putamen of PD patients compared to both healthy controls and essential tremor individuals. No overlap was observed between putamen values in PD and normals. No differences were found between controls and essential tremor subjects. These data confirm that measurements of DAT binding can provide an accurate and highly sensitive measure of degeneration in the dopamine system in PD.
 
Article
Amantadine has been proved to be beneficial in Parkinson's disease. Although it is still uncertain which neurochemical events are modified at therapeutic doses, an increase in dopaminergic tone secondary to NMDA receptor blockade and a direct inhibition of the glutamatergic overactivity have been suggested to be involved in its clinical effects. The aim of this study was to evaluate the effects of amantadine on the dopaminergic system by measuring the in vivo binding of [11-C]raclopride to D2 dopamine receptors in the basal ganglia of 6 patients with idiopathic Parkinson's disease. Each patient underwent a PET study, before and after 14 days of treatment with amantadine (200 mg/day). Repeated treatment with therapeutic doses of amantadine induced a moderate increase in the in vivo binding of [11C]raclopride in the putamen of PD patients. This observation indicates that in PD patients, 200 mg/day amantadine does not produce an increase in extracellular levels of dopamine sufficiently to inhibit raclopride binding or that, if present, is it masked by a concurrent increase in receptor availability, as recently reported in rat striatum.
 
Article
Neuroimaging studies of striatal dopamine transporters (DAT) have shown that this measurement is a specific marker of dopaminergic degeneration in patients with Parkinson's disease. However, little data is available in subjects with early disease onset, particularly in those with autosomal recessive parkinsonism. We measured striatal DAT binding in 10 patients with early onset PD (onset <40 years) and in 10 with late onset PD (onset >50 years) using PET and the tracer [(11)C]FECIT. One early onset subject presented a mutation in the parkin gene consistent with autosomal recessive parkinsonism. Data were compared with those of 15 control subjects. We found a comparable decrement of striatal DAT binding in early and late onset PD. Loss was widespread and bilateral in the patient carrying the Park2 mutation, suggesting a different pattern of denervation in these individuals.
 
Pedigree of the family. a Pedigree of PARK2 family, b pedigree of PARK6 family, c pedigree of PARK7 family 
Clinical features of three affected families members and a patient with IPD 
Article
Mutations in the Parkin, PINK1, and DJ-1 genes can cause autosomal recessive early onset Parkinsonism. We studied three families with the mutations of the Parkin, PINK1 and DJ-1 genes, respectively, with a dopamine transporter ligand [(11)C]-CFT positron emission tomography. A marked bilaterally and dissymmetrically decrement of [(11)C]-CFT uptake was found in all these patients, and putamen as well as caudate nucleus was affected. We also found asymptomatic Parkin and PINK1 heterozygotes showed a mild but significant decrement in [(11)C]-CFT uptake, but this phenomenon was not found in the DJ-1-heterozygotes. Our results suggested the three autosomal recessive forms of early onset are similar to each other on pathophysiological grounds, a sub-clinical disease process in Parkin and PINK1-heterozygotes, but not in DJ-1-heterozygotes.
 
Article
Many lines of research have suggested a relationship between migraine with aura (MA) and patent foramen ovale. Right-to-left shunt (RLS) of blood might explain both the occurrence of MA attacks, as well as the increased risk of ischaemic stroke in these patients. We evaluated the prevalence and the characteristics of RLS in a series of 120 MA patients, who were studied with contrast-enhanced Transcranial Doppler examination. We found RLS in 61 of them. A latent RLS was found in 28%, a permanent RLS in 72%, a shower-curtain pattern was detected in 52% of the studied patients.
 
Article
We used qualitative visual assessment and semiquantitative measures of striatal DAT binding using [(123)I]FP-CIT-SPET in 85 patients with Parkinson's disease (PD). We compared these two assessments and their correlation with PD clinical progression. SPET imaging was visually classified by a nuclear medicine physician as normal or abnormal pattern grade I, II and III, in relation to a different degree of radioligand reduction uptake. Nineteen patients presented abnormal grade I (group 1), 53 grade II (group 2) and 13 grade III (group 3). The UPDRS III motor score, the H-Y score, the rigidity and bradykinesia subscores were significantly different among the three groups. Post hoc analysis showed that all values of these clinical parameters were higher in group 3 than in 2 and 1. All clinical indices were also significantly higher in group 2 than in group 1. This means that groups 3 and 2 were clinically more severely affected. No significant differences among the 3 groups were observed for age or duration of disease. Values of the mean striatum uptake were also significantly different among the three groups. Post hoc analysis revealed significantly lower values of the mean striatum uptake in group 3 with respect to groups 2 and 1; values were also significantly lower in group 2 than in group 1. We conclude that our findings of good consistency between visual and semi-quantitative assessment may help simplify the evaluation of striatal DAT binding in PD in a clinical routine setting.
 
Article
We used SPECT and the tracer (123)I-Ioflupane to measure dopamine transporter (DAT) binding in the caudate nucleus and the putamen of 70 patients with Parkinson's disease (PD), 10 with multiple system atrophy (MSA-P type), and 10 with progressive supranuclear palsy (PSP). Data were compared with 12 age-matched control subjects. We found significant reductions in mean striatal values in all three forms of parkinsonism. However, decrements were significantly greater in PSP (0.51+/-0.39, p<0.01) compared with MSA-P (0.70+/-0.33) and PD (0.95+/-0.38). No differences were found between MSA and PD. Putamen/caudate ratios were greater in PSP (0.83+/-0.12, p<0.01) than in PD (0.51+/-0.11), suggesting a more-uniform involvement of dopamine nerve terminals in both caudate nucleus and putamen. Our results confirm that DAT binding can provide an accurate and highly sensitive measure of dopamine degeneration. PSP patients may show a different pattern of neuronal loss compared with MSA and PD.
 
Normal uptake pattern of 123 I-MIBG scintigraphy (anterior view at 4 h after injection of 111 MBq); the uptake of the radiopharmaceutical in salivary glands, liver, heart and lungs is considered as physiological (Image from Nuclear Medicine Unit of Maggiore Hospital of Bologna, Italy)  
An anterior view at 4 h after injection of 111 MBq of 123 I-MIBG. MIBG scintigraphy was performed in a patient with cognitive impairment for differential diagnosis between dementia with Lewy bodies and other neurodegenerative diseases with cognitive impairment. No uptake of the radiopharmaceutical was observed in the heart suggesting a Lewy body disease (LBD) (Image from Nuclear Medicine Unit of Maggiore Hospital of Bologna, Italy)  
An anterior view at 4 h after injection of 111 MBq of 123 I-MIBG. MIBG scintigraphy was performed in a patient with parkinsonism for differential diagnosis between Parkinson's disease and other parkinsonian syndromes: the uptake of radiopharmaceutical observed in the heart was normal excluding a Parkinson's disease (PD) (Image from Nuclear Medicine Unit of Maggiore Hospital of Bologna, Italy)  
An anterior view at 4 h after injection of 111 MBq of 123 I-MIBG. MIBG scintigraphy was performed in a patient with parkinsonism for differential diagnosis between Parkinson's disease and other parkinsonian syndromes: no uptake of the radiopharmaceutical is observed in the heart suggesting a Parkinson's disease (PD) (Image from Nuclear Medicine Unit of Maggiore Hospital of Bologna, Italy)  
Interpretation of 123 I- MIBG scintigraphic findings in differential diagnosis between Lewy body disease (LBD) and other movement disorders  
Article
Radiolabeled metaiodobenzylguanidine (MIBG) is an analog of guanethidine and is taken up by the postganglionic presynaptic nerve endings. MIBG uptake in the heart correlates with adrenergic function, which can be reduced in Lewy body diseases. We described the recent developments in innervation imaging using (123)I-MIBG scintigraphy in Lewy body diseases including Parkinson's disease and dementia with Lewy bodies. Particularly, we underlined the role of MIBG scintigraphy in differential diagnosis of movement disorders. As described by recent studies, MIBG scintigraphy is a valuable diagnostic tool for differentiation between Lewy body diseases and parkinsonian syndromes or other movement disorders with parkinsonism. Furthermore, this method may provide a powerful differential diagnostic tool between dementia with Lewy bodies and Alzheimer's disease. We also reported the results of clinical investigations about the correlation between characteristics of Parkinson's disease and myocardial MIBG uptake.
 
Article
Toll-like receptors (TLRs) are important mediators of inflammatory responses by recognition of many pathogen-related molecules and endogenous proteins related to immune activation. Accumulating data have recently pointed out the role of neuroinflammation in Parkinson's disease (PD) pathogenesis. In the present study, we investigated the potential role of the TLR9 -1237 T/C and TLR2 -194 to -174 del polymorphisms in PD. We studied a total of 333 individuals, 215 Greek patients with sporadic PD and 118 control subjects, using a polymerase chain reaction-restriction fragment length polymorphism method. No statistically significant differences were found between PD patients and control subjects for the TLR9 -1237 T/C genotypes or alleles. Regarding the TLR2 -196 to -174 del polymorphism, the del/del genotype and the del allele were overrepresented in the PD group compared to controls, however, this result did not reach statistical significance (P = 0.087). Further studies investigating the TLR-inflammatory background of PD are awaited to provide important insight into the aetiology of the disease.
 
Article
The aim of this study was to assess the ability of a single SPECT performed in the early stage of Parkinson's disease (PD) to predict disease severity in 19 patients with early PD. [(123)I]-FP-CIT striatal uptake was expressed as a ratio of specific:nonspecific uptake for defined brain areas. Clinical severity was determined by the UPDRS at baseline and 12-15 months following the SPECT procedure. [(123)I]-FP-CIT uptake in the contralateral putamen and striatum was correlated with UPDRS score at baseline, with a more significant correlation after 1-year interval. [(123)I]-FP-CIT uptake in all areas was correlated with bradykinesia and rigidity subscores only at follow up visit. Significant correlations were found between [(123)I]-FP-CIT uptake in the contralateral striatum, putamen and caudate and the difference between motor scores of 1-year interval (DeltaUPDRS). These results suggest that disease severity might be anticipated by a single SPECT at an early stage of the disease.
 
Article
Transsphenoidal surgery (TSS) is a well recognised treatment for secreting pituitary adenomas, however a very wide variation of clinical outcomes and recurrence rates has been reported, depending on the different criteria used to define the cure. We reported the clinical outcome of a large series of patients operated on for a secreting pituitary adenoma according to the most recent stringent criteria of biochemical remission nowadays accepted. One hundred and twenty-five consecutive patients with a secreting pituitary adenoma (42 PRL-, 67 GH- and 16 ACTH-secreting adenomas) who were operated on by the two same neurosurgeons were considered for the study. Biochemical remission of disease was achieved in 56% of patients; 78% for patients with microadenoma and 47% for patients with macroadenomas, respectively. No cases of mortality or major immediate postoperative complications were observed. Tumour size, high hormone levels and dural invasion were significantly correlated to a poor surgical outcome. The recurrence rates ranged between 0 and 24%, being higher for PRL-secreting tumours. In conclusion, TSS is safe and effective in secreting pituitary tumours. It is still the first treatment for GH- and ACTH-secreting adenomas, whereas in patients with prolactinomas, surgery should be reserved for cases of resistance or intolerance to dopamine agonists.
 
Article
So far, subjects heterozygous for PAHX mutations are regarded as non-symptomatic. In the 24-year-old, HIV-negative daughter and the 26-year-old, HIV-negative son of a patient with Refsum disease due to the homozygous c.135-2A>G transition at the splice site before exon 3 of the PAHX gene, slight abnormalities suggestive of the disease became apparent. The daughter reported a single fever cramp in childhood, recurrent, short-lived amaurotic episodes after getting up from supine, short-sightedness, hypoacusis, and restless legs. The son complained about restless legs, hyperhidrosis, hypoacusis, and bulbar oscillations. Though both children carried the same mutation as their mother in the heterozygous form, clinical neurologic examination, nerve conduction studies and serum phytanic acid concentration were normal in both of them, implying that the described abnormalities were not causally related to the PAHX mutation. In the absence of elevated phytanic acid concentrations, clinical neurologic abnormalities in heterozygous relatives of Refsum patients are not attributable to heterozygosity for PAHX mutations.
 
Article
Detection of 14-3-3 protein in cerebrospinal fluid (CSF), in combination with findings on electroencephalography (EEG) and magnetic resonance imaging (MRI), is a highly sensitive and specific diagnostic test for sporadic Creutzfeldt-Jakob disease (CJD) in patients premortem. We present a case of classic, sporadic CJD, confirmed on autopsy and by Western blot. However, all routine premorbid testing was negative, the CSF was negative for the 14-3-3 protein, EEG did not show periodic sharp wave complexes (PSWC), and MRI failed to show hyperintense signal in the basal ganglia. Thus, laboratory support for the diagnosis of CJD was not obtained premortem. The chances of all three diagnostic testing modalities to be negative in a single case of sporadic CJD are extremely remote. Autopsy with neuropathologic confirmation remains the only definitive way to make a diagnosis of CJD.
 
Linear regression: BDI-2 and MIDAS changes as predictors of WHO-DAS-2 change 
Article
This paper aims to evaluate changes in disease severity, disability and mood state in patients with chronic migraine associated to medication overuse (CM-MO). MIDAS was used for assessing disease activity, WHO-DAS-2 for disability, DBI-2 for mood state. ANOVA was used to test change over time; t-test to assess follow-up differences in WHO-DAS-2 and BDI-2 between patients with MIDAS ≤20 and ≥21. Change in MIDAS, WHO-DAS-2 and BDI-2 scores were computed: Pearson's index was used to assess correlation between them; linear regression to assess change in WHO-DAS-2, using MIDAS and BDI-2 change as predictors. Mean MIDAS decreased significantly (from 101.9 to 52.0). In 26.1 % of the sample, MIDAS fell below 21 at follow-up: these patients had lower WHO-DAS-2 score. WHO-DAS-2 change was little correlated to MIDAS change and strongly correlated to changes in BDI-2 scores. 57.1 % of WHO-DAS-2 change variance is explained by change in BDI-2 and MIDAS scores. There was a clear clinical improvement 14 months after detoxification, and a modest reduction in disability which is explained by reduced disease activity and improved mood state. An appropriate treatment of CM-MO, based on detoxification and prophylaxis, is likely to reduce disease burden: recognition and treatment of mood problems may be a key factor to reduce disability.
 
Article
The objective of this study was to verify the adherence of Italian family physicians and neurologists to the Guidelines on Diagnosis of Dementia of the Italian Society of Neurology. A multicentre survey was carried out, in 72 neurological centres. The centres included at least 15 consecutive subjects suspected of having a dementia. The adherence of family physicians to the guidelines was poor. Neurologists performed a complete neuropsychological evaluation in a minority of the cases. Patients who had a decrease of Mini Mental Status Examination scores after six months higher than or equal to 4 were more represented among those patients for whom one or more recommendations were not respected. In Italy the adherence to the Guidelines on Diagnosis of Dementia and AlzheimerValidation studys Disease of the Italian Society of Neurology is very poor for family physicians (GPs) and satisfactory, albeit improvable, on the part of neurologists. Respect for the guidelines might improve the outcome of patients with dementia.
 
Article
The Five-Point Test is one of the various measures of figural fluency functions that have been developed as nonverbal analogues to word fluency tasks, and used in neuropsychological assessment to evaluate the ability to initiate and sustain mental productivity, and to self-monitor and regulate responding in the visual-spatial domain. The aim of the current study was to collect normative data for a version of the Five-Point Test (M-FPT) administered to a sample of Italian healthy adults aged 16-60 (n = 332). Performance on the M-FPT was scored by computing the cumulative number of unique designs (UDs) performed on a 3-min administration time. Two supplemental scores were also computed: (a) the cumulative strategies (CSs) consisting with the number of UDs incorporated into enumerative or rotational strategies; (b) the error index (ErrI), consisting with the percentage between the number of perseverative or rule-breaking errors and the number of designs overall. Multiple regression analyses revealed a significant effect of age and education, but not gender, for both UDs and CSs. Equivalent scores and cut-off scores were then determined for UDs and CSs. Descriptive statistical analyses and cut-off scores were reported for ErrI. The availability of normative data for the M-FPT will be valuable in clinical settings for assessing of executive dysfunctions on the visual-spatial subdomain of subjects with brain injury. However, in order to increase the usefulness of the test, the upper limits of the age range of the normative sample should be widened. Moreover, further analyses should be required for determining the inter-rater and test-retest reliability for M-FPT performances, and providing evidence of the sensitivity of this measure to brain disturbances generally and to frontal lobe dysfunction specifically.
 
Article
The aims are to evaluate electrodiagnostic testing (EDX) requests and verify if presence, consistency and agreement of referral diagnosis could be predicted by patient demographic findings and referring physician typology, and if there were differences in respect to our previous study performed 16 years ago. The study concerns EDX requests referred to two electromyography labs during the year 2011. Differences between findings of general practitioners (GPs) versus specialists' requests and between this study with the previous were assessed. Multivariate logistic regression was performed to calculate odds ratio to assess the strength of association between presence, consistency and agreement of referral diagnosis with patient demographic findings and referring physician typology. We evaluated EDX requests of 1,586 patients (mean age 56 ± 16.7 years, 58.8 % women), 1,050 (66.2 %) were referred by GPs and 536 (33.8 %) by specialists. The suspected diagnosis was reported in 1,033 (65.1 %) requests, the overall consistency was 79.9 % and agreement was 71.9 %. Presence, consistency and agreement of referral diagnosis were predicted by physician's typology (specialist). Only if the suspected diagnosis was carpal tunnel syndrome, consistency and agreement were high regardless of doctor's typology. The physicians, especially GPs, who reported the referral diagnosis decreased during the past 16 years. A diagnostic test, including EDX, should be considered mainly if it fits into the best diagnostic strategy. The neurophysiologist should decide if EDX is useful, make the best decision on further management, and not submit patients to unnecessary and uncomfortable procedures. This choice of behaviour could be questionable and may lead to ethical and deontological problems.
 
Article
The objective was to evaluate the outcome of microsurgical "pure" lesionectomy in patients with supratentorial cavernous angiomas presenting with seizures. For this retrospective study 163 patients with cavernoma-related epileptic seizures were selected. They all underwent surgery in a single institution between 1988 and 2003. A microsurgical frame/frameless guided minimally invasive transulcal "pure" lesionectomy was performed. The haemosiderin stained gliotic brain parenchyma that was usually found surrounding the lesion was not removed. Among the 99 patients with epilepsy and longer clinical history, 68 (68.7%) were found completely to be seizure-free, 10 (10.1%) presented sporadic and less frequent seizures and 17 (17.1%) remained unchanged. Sixty-three out of 64 (98.4%) patients who experienced only single or sporadic seizures were found to be completely seizure-free after surgery. Five patients were lost at follow-up (mean 48 months, range 0.5-14 years). Long-term morbidity was 1.8%. Mortality was null. No haemorrhagic episodes were observed during follow-up. Pure lesionectomy prevents bleeding and development of epilepsy in patients that receive early surgery after the epileptic onset. In most of the epileptic patients with a good concordance between the electroclinical data and the location of the angioma, good results can be achieved by this kind of surgery so that more invasive and costly studies to find and remove the epileptogenic cerebral parenchyma seem justified only after lesionectomy fails.
 
Article
We observed two families with a dominantly inherited complex neurological syndrome with onset in adulthood. Family F included 9 affected in four generations. One patient showed prominent anticipation of onset age. Onset was with cerebellar signs followed by dementia, psychiatric symptoms, seizures, and extrapyramidal features. Family M included 14 affected individuals in five generations. Presenting symptoms were either psychiatric and cognitive impairment or a cerebellar syndrome. Extrapyramidal features, dysphagia, incontinence, seizures, and myoclonus may occur. In both families magnetic resonance imaging showed marked atrophy of the brain and cerebellum. Molecular analyses demonstrated an expanded CAG/CAA repeat in the in the TATA box-binding protein (TBP) gene (SCA17).
 
Article
The importance of visual evoked potential (VEPs) and electroencephalography for diagnosing and distinghishing the infantile (INCL), late-infantile (LINCL) and juvenile (JNCL) forms of neuronal ceroid lipofuscinoses (NCL) is well established. Variant forms with protracted clinical courses and atypical symptoms have been described recently, whose neurophysiological characteristics sometimes overlap those of LINCL and JNCL. It is unclear whether these variant forms are due to phenotypic variability of known genetic defects, or represent new mutations. Twenty-eight NCL patients have been diagnosed at our institute; a proportion of them were investigated genetically. In 17 we performed neurophysiological investigations including VEPs, brainstem auditory (BAEP) and upper limb somatosensory (SEP) evoked potentials. We found typical and diagnostic electrophysiological involvement of the visual system in 8 patients with classic forms of NCL. Furthermore, the distinctive features of the multimodal evoked potentials in most of the six patients with variant NCL suggest that these are distinct genetic entities.
 
Article
The aim of this study was to investigate the functional anatomy of decision-making during the Iowa Gambling Task in patients with Parkinson's disease. We used event-related functional magnetic resonance imaging (fMRI) during a computerized version of IGT to compare 18 PD patients on dopaminergic medication in the ON state and 18 healthy control subjects. Our analyses focused on outcome evaluation following card selection, because we expected this aspect of decision-making to be impaired in PD patients. The PD patients exhibited lower activation of the left putamen than the control group as a reaction to penalty. Using psychophysiological interaction analysis, we identified decreased functional connectivity between the right globus pallidus internus and the left anterior cingulate gyrus in the PD group. In contrast, increased connectivity between these structures was observed after penalty in the control group. Our results suggest altered functioning of the basal ganglia and their connections with the cortical structures involved in the limbic loop (e.g., the limbic fronto-striatal circuit of the basal ganglia) during decision-making in PD patients. Differences in the response to loss could be associated with insufficient negative reinforcement after a loss in PD patients in the ON state in comparison to a healthy population.
 
Article
There was fewer paper about the relation between the Hamilton Depression Rating Scale (17 Items, HDRS-17) factors and stroke outcomes. Our aim was to investigate the influence of total score and factors of HDRS-17 on outcome of ischemic stroke at 1 year. A total of 1,953 patients with acute ischemic stroke were enrolled into a multicentered and prospective cohort study. The HDRS-17 was used to assess symptoms at 2 weeks after ischemic stroke. The Modified Ranking Scale (mRS) scores of 3-6 points and 0-2 points were regarded as poor outcome and benign outcome, respectively. At 1 year, 1,753 (89.8 %) patients had mRS score data. After adjusting for the confounders, patients with a total HDRS-17 score of ≥8 had a worse outcome at 1 year (OR = 1.62, 95 % CI 1.18-2.23). Symptoms of suicide (OR = 1.89, 95 % CI 1.27-2.83), decreased or loss of interest of work (OR = 1.89, 95 % CI 1.38-2.58), retardation (OR = 1.74, 95 % CI 1.27-2.38), psychic anxiety (OR = 1.72, 95 % CI 1.26-2.34), and agitation (OR = 1.61, 95 % CI 1.08-2.40) increased the risks for poor outcome by >60 %, respectively. Depressed mood, somatic anxiety, somatic symptoms-gastrointestinal, and early insomnia also increased the risk for poor outcome by nearly 50 %, respectively. A total HDRS-17 score of ≥8, and suicide, decreased or loss of interest of work, anxiety, agitation, retardation, depressed mood, somatic anxiety, somatic symptoms-gastrointestinal, and early insomnia of the HDRS-17 factors at 2 weeks after ischemic stroke increase the risk for poor outcome at 1 year.
 
Portrait of an unknown boy. Miniature by Richard Cosway, showing a young Augustus d'Esté, according to several sources of information 
Medulla spinalis with sclerotic parts, from Carswell's pathological anatomy (1838) 
Facsimile of a part of the text in the diary 
Article
The personal diary of Sir Augustus d'Esté, born 1794 grandson of King George III of England, reveals a medical history strongly suggesting that Augustus suffered from multiple sclerosis (MS). It could well be the first record of a person having this disease. Charcot coined the term sclérose en plaques 20 years after the death of this patient in 1848. The onset of this man's MS seems to have been in 1822 with bilateral optic neuritis, the disease gradually developing in the classic manner with bouts derived from different loci in the central nervous system and eventually a secondary progressive form with paraparesis, sphincter incontinence, urinary problems and impotence. In 1941, Firth highlighted the case of Augustus d'Esté and later wrote a description of the pathology including a discussion on the aetiology of MS. No previous medical records have given such a characteristic picture of MS as this.
 
Article
As proinflammatory cytokines released during ischaemia are detrimental to the brain, the study aimed to evaluate serum interleukin-18 (IL-18) levels in stroke patients and to investigate the relation between these and epidemiological and clinical data. The study comprised 23 ischaemic stroke patients and 15 controls. Blood sampling for IL-18 determination and for chemistry, and brain CT were performed within 24 h of stroke, while neurological stroke severity and functional disability were estimated, respectively, with the Scandinavian stroke scale (SSS) and Barthel index (BI) within the same interval and two weeks later. There were higher serum IL-18 levels in stroke patients. These correlated with erythrocyte sedimentation rate (ESR), brain CT hypodense area volumes, and SSS and BI scores calculated at both studied times. Moreover, IL-18 levels were higher in patients with non-lacunar stroke subtype than in those with lacunar strokes. The results suggest that IL-18 is involved in stroke-induced inflammation and that initial serum IL-18 levels may be predictive of stroke outcome.
 
Article
We examined a group of 18 consecutive patients with spontaneous cerebrospinal fluid leak syndrome (SCSFLS) and investigated clinical, MRI, radioisotope findings and therapeutic outcome of this syndrome.
 
Age distribution of 604 cases of TIA and stroke 
Scandinavian Stroke Scale and Modified Rankin Scale at entry in 507 cases of stroke 
Risk factors in 604 cases of stroke and TIA 
Diagnostic work-up and procedures in 604 cases of stroke and TIA 
Article
This observational prospective multicentre study aims to describe a hospital-based database collecting information about clinical features, management and follow-up of stroke patients. In 18 neurological departments (mostly first-referral) in Piedmont and the Aosta Valley, Italy, between May and July 1999, 604 consecutive patients (97 TIA, 443 ischaemic, and 64 haemorrhagic stroke) were studied. Ischaemic stroke aetiologies were as follows: large-artery atherosclerosis (148), small-artery occlusion (133), cardioembolism (76), other causes (13) and undetermined (73). According to Bamford's classification, 164 were PACI, 126 LACI, 87 TACI and 66 POCI. The diagnostic workup and management of patients is described; only 4% of patients did not receive a CT scan. Four hundred and three patients were discharged to their home, 78 to a rehabilitation unit, 44 to long-term institutional care, 20 to other wards and 59 died while in hospital. After six months, 10 patients were lost to follow-up, 499 were alive and 95 had died. The SINPAC database allows for evaluation of current practice of care in a first-referral stroke population.
 
Article
In 31 patients with probable Alzheimer's disease (AD), 19 with probable vascular dementia (VaD) and 20 with Possible AD and Possible VaD, cerebrospinal fluid (CSF) tau levels hyperphosphorylated at threonine 181 (Ptau) were measured by ELISA. Thirty-six age-matched subjects were used as controls. The severity of the cognitive decline was assessed at the time of CSF analysis and after a 12-month follow-up. The groups had comparable age, degree of cognitive impairment and disease duration; these parameters were not related to P-tau levels. P-tau discriminated between demented patients and controls, but no significant difference emerged between AD and the other groups. By contrast, higher P-tau values were found to predict, independently of the clinical diagnosis, a more rapid evolution of cognitive decline. Whether these findings are due to a lack of CSF P-tau specificity or to the low reliability of clinical and radiological criteria remains unclear. P-tau may be useful in the evaluation of disease evolution, by predicting the rate of cognitive decline.
 
Article
Filippo Lussana's scientific activities are neglected in neurological field. His activity could be divided into two phases: as a medical practitioner and the academic period, as a clinical neurophysiologist. The focus of his various research studies was the central nervous system, including balance disorders (the role of the cerebellum and semicircular canals), taste innervation, pain and speech disorders (theories of brain localisation). Lussana's clinical method and direct dealings with patients laid the groundwork for his subsequent academic activities as a neurophysiologist, in Parma and later in Padua. Influenced by phrenological theories, he also conducted interesting studies on synaesthesia for which he determined a brain site. He contributed to the neurophysiology of taste, emphasising the role of the facial nerve. With his study on muscle sense, he also joined the debate on the role of the cerebellum in balance, setting the foundation for later studies on this organ by Luigi Luciani.
 
Article
2011 marks the 80th anniversary of the death of Constantin Alexander von Economo who conducted advanced research on the cytoarchitectonics of the brain. This Austrian neurologist and the pioneer of aviation described encephalitis lethargica, discovered the spindle neurons, and postulated the existence of the sleep and wakefulness centre in the brain. What is more he realized two of the biggest dreams of humankind: conquering space and getting to know the secrets of the human brain.
 
Focal ischemia areas (H&E, 910), mononuclear cell infiltration (H&E, 920), vascular congestion (H&E, 920), and neuronal degeneration (H&E, 940) were observed in the brain tissues of the I/R group 
Decreases in mononuclear cell infiltration (arrows; H&E, 920) and neuronal degeneration (H&E, 940) were observed in the GA?I/R group 
Immunohistochemical expression of caspase-3 in all experimental groups. The number of caspase-3-positively stained cells decreased in the GA?I/R group (e, f) compared with the I/R group (c, 
Article
This study investigated the effects of 18β-glycyrrhetinic acid (GA) on neuronal damage in brain tissue caused by global cerebral ischemia/reperfusion (I/R) in C57BL/J6 mice. All subjects (n = 40) were equally divided into four groups: (1) sham-operated (SH), (2) I/R, (3) GA, and (4) GA+I/R. The SH group was used as a control. In the I/R group, the bilateral carotid arteries were clipped for 15 min, and the mice were treated with the vehicle for 10 days. In the GA group, mice were given GA (100 mg/kg) for 10 days following a median incision without carotid occlusion. In the GA+I/R group, the I/R model was applied to the mice exactly as in the I/R group, and they were then treated with the same dose of GA for 10 days. Cerebral I/R significantly induced oxidative stress via an increase in lipid peroxidaitons and a decrease in elements of the antioxidant defense systems. However, GA treatment was protective against the oxidative effects of I/R by inducing significant increases in antioxidant defense systems and a significant decrease of lipid peroxidations. Additionally, cerebral I/R increased the incidence of histopathological damage and apoptosis in brain tissue, but these neurodegenerative effects were eliminated by GA treatment. Therefore, the current study demonstrated that GA treatment effectively prevents oxidative and histological damage in the brain caused by global I/R. In this context, GA may be useful for the attenuation of the negative effects of global cerebral I/R and, in the future, it may be a viable and safe alternative treatment for ischemic stroke in humans.
 
Article
Genome-wide association studies (GWAS) identified multiple single-nucleotide polymorphisms (SNPs) that are associated with the pathogenesis of Alzheimer's disease (AD). As replication in independent studies remains the only way to validate proposed GWAS signals, we detect SNPs reported in the GWAS, in order to explore their association with sporadic AD (SAD) in the Chinese population. We analyzed genotype and allele distributions of 19 SNPs reported in GWAS in 191 SAD patients and 180 healthy controls. We found that higher frequencies of rs10868366 G and rs7019241 C carriers were observed in SAD patients compared with controls (rs10868366 G: P = 0.026, odds ratio (OR) = 1.4, 95% confidence intervals (CI) 1.0-1.9; rs7019241 C: P = 0.019, OR 1.4, 95% CI 1.6-1.9). Furthermore, rs10868366 G/T and rs7019241 C/T in GOLPH2 were in strong linkage disequilibrium and formed a relative protective factor rs10868366 T/rs7019241 T and a relative risk factor rs10868366 G/rs7019241 C. For SNP rs3826656 in near gene 5' region of CD33, the results revealed that in subjects with APOE ε4 alleles, the A allele was associated with a reduced risk of SAD compared with the G allele (OR 0.479; 95% CI 0.263-0.870, P = 0.015), and AA genotype was associated with a reduced risk of SAD compared with the genotype AG + GG (OR 0.395; 95% CI 0.158-0.659, P = 0.008). Our results support the view that rs10868366 and rs7019241 in GOLPH2 and rs3826656 in near gene 5' region of CD33 are significantly associated with SAD in the north Chinese Han population.
 
Article
A patient self-rated 19-item wearing-off questionnaire (WOQ-19) was shown to be a potent screening tool for wearing-off (WO) in patients with Parkinson's disease. As part of the early detection of wearing-off in Parkinson's disease study, we preliminarily performed a linguistic and a psychometric validation of an Italian version of the WOQ-19. Moreover, we assessed the sensitivity and specificity of the WOQ-19 in the office-based settings. The psychometric validation study included assessment of discriminant ability, internal consistency and test-retest reliability. The intraclass correlation coefficient (ICC) and the Cronbach's Alpha were assessed. The WOQ-19 sensitivity and specificity were calculated in respect to the physician assessment of WO, taken as the gold standard. The Italian version of WOQ-19 was found easy to understand by ≥80% of the patients. The number of WO-related symptoms detected by WOQ-19 was 7.5 ± 3.2 in patients with WO and 1.6 ± 2.6 in patients without WO (p < 0.0001). Cronbach's alpha was equal to 0.868 for the total number of WO symptoms. The ICC value was equal to 0.858 for WO-related symptoms as a whole. The diagnostic ability study recruited 207 patients: for a WOQ-19 cut-off ≥2, the sensitivity was equal to 0.881 and the specificity was 0.674. This is the first validation of WOQ-19 in Italian, with excellent linguistic validity and psychometric properties. WOQ-19 was confirmed to be reliable in WO detection.
 
Article
Without Abstract
 
Article
The objective of the study is to ascertain the rationale for the diagnosis of postencephalitic parkinsonism (PEP) at Boston City Hospital's Neurological Unit (1930-1981). 5,270 discharge summaries were evaluated for the diagnoses of PEP. Sixteen cases of PEP were identified; the diagnosis of PEP was justified in approximately half of these cases based on the published criteria for distinguishing PEP from Parkinson's disease (PD). In conclusions, the absence of a clear justification for the diagnosis of PEP in many of the 16 cases suggests that the accepted relationship between encephalitis lethargica and PEP may be less definitive than currently believed.
 
Article
A shorter four-set (A, B, C, D) version of Raven's progressive matrices 1938 (PM38) has gained increasing use in neuropsychological assessment. No normative data spanning across a wide age range are, however, available. This study collected norms for the shorter version of PM38, established an inferential cut-off value and derived equivalent scores in a sample of 248 individuals from 20 to 89 years of age, evenly distributed across sex, age and education levels. Results showed significant effects of age and education but no effect of sex on performance. These normative data will complement existing norms for other tests, will increase the wealth of neuropsychological tools for which normative data are available for the Italian population, and may be useful in the early detection of individuals at risk of developing dementia.
 
Monthly incidence in Spanish population under surveillance for the period 1998-1999, predictions with 95% percentile values from Poisson regression for the surveillance period, and future predictions based on 1985-1999 data
Structural and functional components of a pilot surveillance system for Guillain-Barré syndrome (GBS) in Spain
Characteristics of 98 patients with Guillain-Barré syndrome reported in 1998-1999, according to motor status one week after clin- ical onset or hospital admission. Values are numbers of patients
Article
Temporal variation in Guillain-Barré syndrome (GBS) warrants monitoring in certain situations. This study sought to describe a public-health-based GBS surveillance service in Spain and conduct pilot surveillance in the period 1998-1999. Neurologists from 11 hospitals countrywide, serving a population of 3.9 million, reported all patients, ages 20 years or over, admitted to hospital with suspected GBS. Cases that did not belong to the designated hospital catchment area or failed to fulfill diagnostic criteria after follow- up were excluded. Reported monthly incidence was compared against predicted incidence obtained from retrospective data (1985-1997) using a reported method based on 97.5% percentile values. Alarm thresholds for 2000 onwards were obtained by applying the same method to the updated 1985-1999 series. During the 2-year period, 98 GBS cases were reported, yielding an overall age-adjusted incidence of 1.26 per 100 000 population, with a breakdown by sex of 1.83 for males and 0.76 for females. Monthly incidence remained below or was similar to the corresponding threshold limit value. Seasonality with highest incidence in winter was more pronounced in the elderly. Preceding events, mainly respiratory infections, were identified in 71% of patients. Pilot two-year GBS surveillance in Spain resulted neither in alarm nor in preventive measures. Adult GBS incidence in Spain might be monitored by a surveillance system set up at short notice when a possible threat is perceived. A monthly incidence of over 3 per 100 000 person-years in the population aged 20 years or older would exceed threshold values.
 
Top-cited authors
Gennaro Bussone
  • University of Milan
Gianni Allais
  • Università degli Studi di Torino
Chiara Benedetto
  • Università degli Studi di Torino
Maria Pia Amato
  • University of Florence
Carlo Caltagirone
  • University of Rome Tor Vergata and IRCCS Fondazione Santa Lucia , Roma