Aldo Quattrone

Lack of association between ubiquitin carboxy-terminal hydrolase l1 gene polymorphism and PD

In 1998, an IL93Met mutation in the ubiquitin carboxy-terminal hydrolase L1 ( UCH-L1 ) gene was identified in a German family affected by PD.1 Recently, others2-4⇓⇓ found that the S18Y polymorphism in exon 3 of UCH-L1 is associated with a low risk of PD. To verify these interesting results, we decided to design a case-control study on the S18Y polymorphism of the UCH-L1 gene using sporadic PD cases. In the meantime, as we were analyzing our samples, a case-control study5 on 142 patients with PD and 142 age- and sex-matched control subjects did not confirm the protective effect found by Maraganore et al.2 In view of these conflicting findings, we reasoned that our contribution may have some weight in defining the role of the UCH-L1 gene in PD. Blood was collected from 169 patients with sporadic PD and 165 control subjects. Patients and control subjects were not matched for age and sex. Patients with PD were consecutively selected starting from January 1999 until September 2000 from among …

Neuroimaging of Essential Tremor: What is the Evidence for Cerebellar Involvement?

Background Clinical observations and electrophysiological studies have provided initial evidence for the involvement of the cerebellum in essential tremor (ET), the most frequent hyperkinetic disorder. Recently, this hypothesis has been reinvigorated by post-mortem studies that demonstrated a number of pathological changes in the cerebellum of ET patients compared with age-matched healthy controls. Advanced neuroimaging techniques have also made it possible to detect in vivo which cerebellar abnormalities are present in ET patients and to reveal the core mechanisms implicated in the development of motor and cognitive symptoms in ET. Objective We discuss the neuroimaging research investigating the brain structure and function of ET patients relative to healthy controls. In particular, we review 1) structural neuroimaging experiments assessing the density/volume of cortical/subcortical regions and the integrity of the white-matter fibers connecting them; 2) functional studies exploring brain responses during motor/cognitive tasks and the function of specific neurotransmitters/metabolites within cortical–cerebellar circuits. Methods A search in PubMed was conducted to identify the relevant literature. Discussion Current neuroimaging research provides converging evidence for the role of the cerebellum in the pathophysiology of ET, although some inconsistencies exist, particularly in structural studies. These discrepancies may depend on the high clinical heterogeneity of ET and on differences among the experimental methods used across studies. Further investigations are needed to disentangle the relationships between specific ET phenotypes and the underlying patterns of neural abnormalities.

Association study between the LINGO1 gene and Parkinson’s disease in the Italian population

Some studies have suggested an overlap of clinical and genetic findings between essential tremor (ET) and Parkinsons disease (PD). The first genome-wide association study in ET showed a significant association with the rs9652490 SNP of the leucine-rich repeat and Ig domain containing 1 (LINGO1) gene. Since patients with PD have higher LINGO1 expression levels compared to healthy controls, and animal models of PD show elevated LINGO1 protein levels after experimentally induced damage in the striatum, it can be inferred that LINGO1 is probably involved in PD pathophysiology. In this study, we performed a genetic association analysis of the rs9652490 and rs11856808 SNPs in Italian PD patients and controls to assess the role of these variants in our population. A total of 567 patients with PD and 468 control subjects were enrolled in five Movement Disorder centers located in Central-Southern Italy. Both variants were significantly associated with PD under a recessive model of inheritance before applying the Bonferroni correction. The GG genotype of rs9652490 and the TT genotype of rs11856808 were less frequent in patients than in controls, suggesting a protective effect against the disease. However, after stringent correction, only the P-values obtained from allele and genotype comparisons of the rs11856808 SNP remained significant. Our findings suggest that LINGO1 plays a certain role in the development of PD in the Italian population and represents an interesting candidate gene responsible for PD, due to its involvement in neurological processes.

A novel founder mutation in the MFN2 gene associated with variable Charcot–Marie–Tooth type 2 phenotype in two families from Southern Italy

Charcot–Marie–Tooth (CMT) disease is the most common hereditary neuropathy. CMT falls into two main forms: the demyelinating CMT type 1 with decreased nerve conduction velocities and the axonal CMT type 2. CMT2 is further subtyped by linkage analysis into >10 loci, with eight genes identified. Recently, mutations in the mitochondrial fusion protein 2 ( MFN2 ) gene were reported in families with CMT2A1 and additional mutations have been detected in other studies, bringing to 42 the total number of different MFN2 mutations described thus far.2–4 In the current study, we report a novel MFN2 mutation shared by two apparently unrelated CMT2 families originating from the same area in Southern Italy. Vertical transmission and male-to-male inheritance were documented in both families, indicating that CMT2 segregates as an autosomal dominant trait. In family 1, 14 affected individuals were identified in four generations (three deceased before the study). After giving informed consent, eight affected individuals and 12 unaffected family members were examined by neurologists and enrolled in the genetic study. All affected individuals showed bilateral pes cavus, lower extremity wasting and steppage gait; only two of eight affected family members (IV-6, IV-7) complained of leg pain. Electrophysiological examination revealed decreased compound motor action potential (CMAP) and sensory action potential (SAP) amplitudes and mildly slowed motor and sensory nerve conductions that were consistent with …

Electroencephalographic and anatomo-clinical evidences of posterior cerebral damage in hypertensive encephalopathy

The authors describe two patients suffering from hypertensive encephalopathy associated with epileptic seizures and anatomo-clinical evidences of posterior cerebral damage. The concordant electroencephalographic features with clinical signs and anatomic lesions of these two patients are discussed, in order to make some considerations about the role played by the blood-brain-barrier damage on the physiopathology of the hypertensive encephalopathy.

Gender effect on non-motor symptoms in Parkinson's disease: are men more at risk?

INTRODUCTION Several gender differences have been reported in Parkinsons Disease (PD). We evaluated the burden of non-motor symptoms (NMS) in PD and the possible gender differences in their occurrence. METHODS The FRAGAMP study is a large multicenter case-control study. PD patients and controls underwent a face-to-face interview and a neurological examination performed by trained neurologists. Presence of NMS was investigated using a standardized questionnaire; cognitive impairment and depression were assessed using the Mini Mental State Examination and the Hamilton Depression Rating Scale respectively. RESULTS 585 PD patients (59.5% men) and 481 controls (34.9% men) were enrolled in the study. All NMS were significantly more frequent among PD patients than controls. PD women showed a significantly higher frequency of depression and urinary disturbances than parkinsonian men; a close frequency among PD women and men was recorded for hallucination, cognitive impairment and sleep disorders. Nonetheless, with respect to the control population, according to logistic regression stratified by sex and adjusted by age, PD men showed a stronger positive significant association with almost all NMS compared to women, excepting for urinary disturbances. The strongest association among PD men was recorded for cognitive impairment (adjusted OR 5.44 for men and 2.82 for women) and depression (adjusted OR 30.88 for men and 12.72 for women). CONCLUSIONS With respect to the general population, presence of NMS was stronger associated with male gender. Our data suggest that the presence of NMS among PD men is more strictly due to the neurodegenerative processes related to PD.

Midbrain meningioma causing subacute parkinsonism

Multiple system atrophy (MSA) is an adult-onset sporadic neurodegenerative disorder characterized by any combination of parkinsonism, cerebellar ataxia, autonomic failure, and pyramidal tract signs.1 Structural brain MRI shows atrophy of the putamen, middle cerebellar peduncle, and pons.1 Although MSA is a rapid progressive disorder with no effective treatment, and it can present with a wider range of clinical features, several neurologic disorders underlying diverse etiologies can be clinically misdiagnosed as MSA and vice versa. Here we present a patient with subacute onset of neurologic symptoms resembling atypical parkinsonism similar to MSA due to a clival meningioma of the posterior fossae.