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Background Spastic Paraplegia type 7 (SPG7) is one of the most common autosomal recessive Hereditary Spastic Paraplegias (HSP); Spastic Paraplegias (SPGs) can present as hereditary ataxias. However, ataxia is frequently the symptom of presentation of many other hereditary/sporadic disorders, such as Multiple system atrophy type C (MSA-C), an α-synuclein sporadic neurodegenerative disorder, in which cerebellar ataxia is one of the main clinical features. Dopamine Transporter imaging (DAT-SCAN), associated with clinical features, can be a helpful tool in order to distinguish MSA-C from other causes of ataxia. Case-presentation We present the case of a 70-year-old man with gait difficulties over a period of 3 years and frequent backward/lateral falls. He also reported urinary urge incontinence, but no symptoms that are compatible with orthostatic hypotension. On neurological examination he showed ataxic gait, spasticity in the left lower limb and trunk and limb ataxia, especially on the left side. Mild hypokinesia was found in all 4 limbs, especially in the left foot. MRI revealed atrophy of the cerebellar hemispheres and vermis. DAT-SCAN imaging revealed bilateral nigro-striatal degeneration, which was compatible with a diagnosis of possible MSA-C. Considering the atypical disease course (the patient walked without any support after 3 years), we carried out a genetic investigation for Ataxia, and a mutation in SPG7 was found. Conclusions DAT-SCAN imaging, evaluated together with the clinical findings, can be useful for differentiating MSA from other possible causes of adult-onset Ataxia. Indeed, patients with MSA-C generally show a decreased uptake of dopamine transporters in DAT-SCAN imaging. Ours is the first case reported in the literature of a patient with SPG7 mutation with nigrostriatal degeneration and a clinical presentation of a possible MSA-C. Performing genetic investigations in patients with an atypical disease course is important to avoid MSA-mimicries. Identifying the correct diagnosis is important not only for prognostic reasons, but also for possible future genetic therapies.

BACKGROUND Parkinson's Disease (PD) is characterized by progressive and disabling symptoms. An impaired oxidative metabolism efficiency was supposed to be involved in the systemic impairment. Rehabilitative treatment represents a valid tool in promoting skeletal muscle's adaptations, even if no solid studies on muscle metabolic features are still available. OBJECTIVE To evaluate the efficiency of skeletal muscle oxidative metabolism in PD patients in comparison with age-matched controls and test the role of an intensive aerobic treatment on muscle oxidative metabolism and its clinical effects. METHODS 60 PD patients and 32 age-matched healthy controls participated. Haematic lactate values were detected during and after a submaximal incremental exercise on treadmill. The number of steps completed during the exercise was recorded. From these patients 10 underwent to an intensive aerobic treatment on treadmill (4 sessions/week for 4 weeks). Haematic lactate values and functional scales were recorded before (T0) and after (T1) treatment. RESULTS At rest no significant difference in hematic lactate values between PD and control subjects was found. Lactate blood levels were significantly higher (p

Deficits in social-cognition processing have been identified during early stages of Huntington Disease (HD), attracting interest on their relevance as possible predictors of neurodegenerative progression. Since the neurotrophin Brain-Derived Neurotrophic Factor (BDNF) and the serotonin (5-HT) transporter (SERT) are known to modulate human adaptive behavior, we appraised these two proteins in mild-HD using blood platelets, with the aim at finding relationships with cognitive/psychosocial skills. Thirteen gene positive and symptomatic patients (9M/4W, HD-stage II, age> 40y) together 11 gender/age matched controls without a concurrent diagnosis of psychiatric disorders, underwent a blood test to determine BDNF storage and membrane-bound SERT in platelets by an ELISA immune-enzyme dosage and [ 3 H]-paroxetine ([ 3 H]-PAR) binding, respectively. Enrolled subjects were concurrently evaluated through a battery of socio-cognitive tests and emotion recognition questionnaires. Results showed greater intra-platelet BDNF (~ +20-22%) in patients versus controls, whereas equilibrium [ 3 H]-PAR binding parameters, maximum density (B max ) and dissociation constant (K D ), did not appreciably vary in the two comparison groups. Cognitive/emotion abilities were found significantly reduced in patients. Additionally, platelet BDNF was unrelated to psycho-cognitive scores, but positively correlated with the illness duration. As well, SERT B max was unconnected to HD signs or socio-cognitive scores, whilst K D s negatively correlated with scores for angry voice recognition in both controls and patients. This pilot study suggests that platelet BDNF and SERT do not specifically underlie psychosocial deficits in stage II-HD, while higher BDNF storage in delayed mild symptoms, would derive from compensatory mechanisms. Supplementary investigations are warranted, by also comparing patients in other illness’s phases.

Background Pisa syndrome (PS) represents an important source of disability in Parkinson's disease (PD). Currently no consensus has been reached on its definition or diagnostic criteria, and therapeutic approaches are unspecific and often futile. Recently the role of abdominal muscles, and in particular of the external oblique (EO), in the pathogenesis of PS was hypothesized. Objectives To evaluate the role of EO and propose a combined therapeutic approach in the management of PS. Methods Ten PD patients with PS underwent a combined protocol based on repeated lidocaine injection in EO and rehabilitation program. Results Our data confirm the primary role of EO muscles in PS pathogenesis and showed an improvement in truncal flexion and balance with a positive impact on patients' quality of life after treatment. Conclusions These data highlight the need for accurate characterization of PS focusing on the role of abdominal muscles and the need for a specific rehabilitation protocol for PS management.

Theory of mind (ToM) is the ability to attribute mental states to one self and others and to understand that others have beliefs different from one's own. Different subcomponents of ToM have also been identified: cognitive and affective. Cognitive ToM refers to the capacity to infer others' beliefs and intentions, while affective ToM implies the ability to appreciate others' emotional states. The aim of this study was to explore ToM in drug-naïve Parkinson's disease (PD) patients and to investigate the effects of chronic dopaminergic therapy on different subcomponents of ToM during a 3 months and 1 year of follow-up. We examined 16 PD patients in three conditions: before (un-medicated) and after dopaminergic therapy (medicated 3 months: T1 and medicated 1 year: T2). We also compared our PD's ToM abilities with 11 healthy individuals. ToM was explored with 5 different tasks: Faux Pas Test, Picture Sequencing Task Capture Story, Emotion Attribution Task, Strange Stories Task, and Karolinska Directed Emotional Faces. Our study confirms that PD patients present deficits in cognitive components of ToM and preserved performances in the affective ones in early stages of disease. We also find a significant effect of dopaminergic therapy on ToM already after 3 months with a good persistency after 1 year of treatment.

The aim of this review is to overview the pharmacological features of neuroleptics experienced in the treatment of Huntington's disease (HD) symptoms. Despite a large number of case reports, randomized controlled trials (RCT) and drug comparison studies are lacking. Areas covered: After evaluating current guidelines and clinical unmet needs we searched PubMed for the term 'Huntington's disease' cross referenced with the terms 'Antipsychotic drugs' 'Neuroleptic drugs' and single drug specific names. Expert commentary: In clinical practice antipsychotics represent the first choice in the management of chorea in the presence of psychiatric symptoms, when poor compliance is suspected or when there is an increased risk of adverse events due to tetrabenazine. Antipsychotics are considered valid strategies, with the second generation preferred to reduce extrapyramidal adverse events, however they may cause more metabolic side effects. In the future 'dopamine stabilizers', such as pridopidine, could replace antipsychotics modulating dopamine transmission.

This study is aimed at relating social cognition in Huntington&rsquo, s Disease (HD) to plasma levels of the social hormone oxytocin (OT). Indeed, HD patients commonly display reduced social skills and OT is involved in bonding behavior and improved recognition of facial emotions. Twelve mild-symptomatic HD patients (stage II Shoulson &amp, Fahn) and 11 gender/age matched controls (healthy controls, HC), without concurrent psychiatric disorders, were investigated at baseline (T0) for OT plasma levels and social cognition through an extensive battery of neuropsychological tests. Social cognition was also re-examined after two years (T1) in 8 of the 12 patients. Results showed a trend for reduced T0-OT levels in HD vs. HC, mean &plusmn, stardard deviation: 6.5 &plusmn, 2.4 vs. 9.9 &plusmn, 7.2 pg/mL, without reaching statistical significance. At T0, patients showed significantly lower performances than controls at the &ldquo, Faux-Pas&rdquo, and &ldquo, Strange Stories&rdquo, tests (p &lt, 0.05, p &lt, 0.01), a reduced perception of visual emotions (p &lt, 0.01) and verbal stimuli (p &lt, 0.01) was also reported, involving anger, fear, and sadness (p &lt, 0.01). Additionally, in the HD population, OT concentrations positively correlated with T1-performances at NeutralFaux-Pas test (p &lt, 0.05), whereas the cognitive Montreal Cognitive Assessment (MoCA) and Mini Mental State Examination (MMSE) scores positively correlated with psychosocial perception at the &ldquo, and Karolinska Directed Emotional Faces (KDEF) tests (p &lt, 0.05). This study, despite its limitations, supports correlations between OT and HD social cognition, suggesting a possible therapeutic use of this hormone. More subjects and additional body tissues/fluids, such as cerebrospinal fluid, should be investigated to confirm this hypothesis.

We investigated the striatal and extrastriatal DAT availability (SPM8) by [123I]FP-CIT-SPECT in 15 PD patients with depression and 35 PD patients without depression. A cluster with significant (p

The Italian Dystonia Registry is a multicenter data collection system that will prospectively assess the phenomenology and natural history of adult-onset dystonia and will serve as a basis for future etiological, pathophysiological and therapeutic studies. In the first 6 months of activity, 20 movement disorders Italian centres have adhered to the registry and 664 patients have been recruited. Baseline historical information from this cohort provides the first general overview of adult-onset dystonia in Italy. The cohort was characterized by a lower education level than the Italian population, and most patients were employed as artisans, builders, farmers, or unskilled workers. The clinical features of our sample confirmed the peculiar characteristics of adult-onset dystonia, i.e. gender preference, peak age at onset in the sixth decade, predominance of cervical dystonia and blepharospasm over the other focal dystonias, and a tendency to spread to adjacent body parts, The sample also confirmed the association between eye symptoms and blepharospasm, whereas no clear association emerged between extracranial injury and dystonia in a body site. Adult-onset dystonia patients and the Italian population shared similar burden of arterial hypertension, type 2 diabetes, coronary heart disease, dyslipidemia, and hypothyroidism, while hyperthyroidism was more frequent in the dystonia population. Geographic stratification of the study population yielded no major difference in the most clinical and phenomenological features of dystonia. Analysis of baseline information from recruited patients indicates that the Italian Dystonia Registry may be a useful tool to capture the real world clinical practice of physicians that visit dystonia patients.

This is an observational cross-sectional study evaluating gait dynamics in patients with Parkinson’s Disease (PD) and severe postural deformities, PD without axial deviations and healthy subjects. Ten PS individuals with Pisa syndrome (PS) and nine subjects with Camptocormia (CC) performed 3-D Gait Analysis and were evaluated with walking and balance scales. Correlations with clinical and functional scales were investigated. Spatio-temporal and kinematic data were compared to ten PD subjects without postural deformities (PP) and ten healthy matched individuals (CG). Data obtained showed decreased walking velocity, stride and step length in PP, PS and CC groups compared to controls. The correlation analysis showed that stride and step length were associated with reduced functional abilities and disease severity in PS and CC groups. Kinematic data revealed marked reduction in range of movements (ROMs) at all lower-extremity joints in PS group. While, in CC group the main differences were pronounced in hip and knee joints. PS and CC groups presented a more pronounced reduction in hip articular excursion compared to PP subjects, revealing an increased hip flexion pattern during gait cycle. Moreover, the increased hip and knee flexion pattern adversely affected functional performance during walking tests. Results obtained provide evidence that step length, along with stride length, can be proposed as simple and clear indicators of disease severity and reduced functional abilities. The reduction of ROMs at hip joint represented an important mechanism contributing to decreased walking velocity, balance impairment and reduced gait performance in PD patients with postural deformities.

In the original article, Gina Ferrazzano was affiliated to Department of Neurology and Psychiatry, Neuromed Institute IRCCS, Sapienza University of Rome, Pozzilli, Italy.The corrected affiliation should be: Neuromed Institute IRCCS, Pozzilli, IS, Italy.

Introduction: In idiopathic Parkinson’s disease (PD), two different clinical phenotypes are usually distinguished: a tremor dominant variant (TD) and an akinetic-rigid type (ART). TD patients are characterized by a slower disease progression and a minor cognitive impairment. Striatal density of DAT, as quantified by FP-CIT SPECT, has been reported to correlate with rigidity and akinesia but not with tremor. Objective: To evaluate FP-CIT uptake in TD and ART phenotypes. Methods: We retrospectively evaluated from our database the pre-synaptic nigro-striatal function of 24 patients with TD-PD and 38 patients with ART-PD who underwent a FP-CIT SPECT within 1 year from disease onset. Results: Disease duration, age at the time of SPECT scan and disease severity as measured with Unified Parkinson’s Disease Rating scale part III (UPDRS III) were not statistically different between the two groups. Putamen contralateral to the most clinically affected side showed a lower FP-CIT uptake in ART patients compared to TD patients. No statistically significant differences emerged when considering bilateral caudate and ipsilateral putaminal uptake, as well as asymmetry indices and caudate/putamen ratios. FP-CIT contralateral putaminal uptake correlated with the severity of rigidity and hypokinesia but not with tremor. Conclusions: These data suggest that other neurotransmitter systems apart from the nigro-striatal dopaminergic system are involved in the generation of Parkinsonian tremor, and they are consistent with previous evidence of a lack of correlation between tremor severity and FP-CIT uptake. Putaminal relative sparing in TD patients could partially explain the slower disease progression reported in this PD phenotype.

We performed 123I-FP-CIT/SPECT and ECD/SPECT in 30 patients with Parkinson's disease with dementia (PDD) and 30 patients with dementia with Lewy bodies (DLB) to evaluate whether presynaptic nigro-striatal function and/or cerebral perfusional pattern is different in these diseases. The striatal uptake of DAT tracer was statistically significantly lower in PDD and DLB with respect to control data (p < 0.0005), however no significant difference was found between PDD and DLB. Patients with PDD and DLB showed a significant reduction of rCBF (p < 0.001) in parieto-occipital and frontal areas, with respect to controls, but the comparison between the two groups did not result in any significant difference by SPM analysis. Finally no correlation was found between any regional perfusional changes and nigro-striatal dysfunction. We conclude that neither studies with 123I-FP-CIT nor ECD/SPECT were able to discriminate between DLB and PDD in vivo.

Apomorphine (APO) is a potent D1 and D2 dopamine agonist. Plasma maximal concentration is reached in 8-16 min with a plasma half-life of 34-70 min. Bioavailability is close to 100%. It has a rapid antiparkinsonian action after subcutaneous (s.c.) administration with a size effect comparable with that of levodopa. Trials of s.c., oral, sublingual, intravenous, rectal, intranasal and iontophoretic transdermal administration of APO have been attempted in Parkinson's disease (PD), each of these routes have shown some potential for clinical effectiveness but the majority of studies indicate that APO intermittent s.c. administration, on which this review is mainly focused, is an effective therapy for the management of motor symptoms in PD, particularly in advanced phases mainly characterized by motor fluctuations, such as wearing OFF and unpredictable "off". Data on the effect of APO on non-motor symptoms in PD patients are limited but there is strong suggestion of a beneficial effect that warrants further investigation.

Huntington disease (HD) is pathologically characterized by a selective neurodegeneration of vulnerable populations of neurons, with an early marked neuronal loss and atrophy in the neostriatum. Dopaminergic innervations of neostriatal neurons originate in the substantia nigra pars compacta. Few studies investigated the neuronal loss and the functional role of the substantia nigra in modulating clinical features in HD.12 patients and 12 age-matched controls underwent SPECT scans with (123)I-FP-CIT and a 1.5 T MRI scan with inversion recovery technique. The association between both clinical and neuropsychological features and striatal uptake and volume of substantia nigra was explored.Striatal (p 0.05), caudate (p 0.05), and putaminal (p 0.01) uptake was significantly lower in patients with respect to controls. Further, the volume of substantia nigra was reduced in HD when compared to controls (p 0.01). No relationship between the volume of SN and tracer striatal uptake was found as well as between clinical and neuropsychological features with the SPECT and MRI results.Our results confirm that the degeneration of nigrostriatal pathway may occur in symptomatic HD patients. If confirmed by larger studies, the lack of any kind of correlation between clinical and neuropsychological features with striatal uptake and volume of substantia nigra suggests that motor and cognitive aspects in HD are not directly related to nigrostriatal degeneration.

Background Impaired social behaviour, partly related to altered perception of emotions, is commonly reported in Huntington’s disease (HD). Aims To evaluate social cognition in symptomatic HD patients and its possible predictors. Methods 12 HD patients (stage II SF Mini Mental State Assessment- MMSE; Frontal Assessment Battery- FAB) and social cognition batteries (Faux Pas test, Bush vignettes test, emotion recognition from both faces expression and verbal stimuli, Strange stories test). After 2 years 8 HD patients were re-evaluated through the same tests. Results HD patients, comparing to controls, showed lower performances in social cognition, particularly in Faux pas test and Strange Stories, and in recognising negative emotions from face expression (KDEF scale) and verbal emotions (p MoCa and MMSE showed positive correlation with social cognitive tests. At the follow up there were no significative differences in motor and cognitive scales (baseline: MoCa 18.6 ± 4.7, MMSE 26.5 ± 2.2, UHDRS 35.2 ± 8.2); (Follow-up: MoCa 19.8 ± 5.6, MMSE 25.5 ± 3.4, UHDRS 36 ± 11.2). Statistical analysis revealed a negative correlation between CAG and Bush vignettes Score (p Conclusions The present study, albeit limited by small sample size, confirms an impairment of social cognition in HD; in addition it suggests CAG expansion and cognitive performances (MoCa and MMSE scores) as possible predictors of social cognition impairment in the course of the disease.

Background Brain Derived Neurotrophic Factor (BDNF) is a neurotrophin implicated in the pathogenesis of neurodegenerative diseases and mood disorders; highly expressed in central nervous system, it can be detected in peripheral tissues such as blood, mainly stored in platelets. Wild type huntingtin (HTT) is believed to activate BDNF transcription and transport, mutated HTT is responsible for reduction of BDNF levels by inhibiting both processes. Several studies investigated BDNF in HD patients demostrating lower values in brain, blood and plasma with respect to controls; however results were not always confirmed and this lack of concordance could be due to extreme variability of sampling collection and laboratory techniques. Aims To evaluate BDNF levels in HD and possible correlations with psychiatric and motor scales by using platelet dosage. Methods 12 patients with symptomatic HD (S&F stage II) and 10 controls, matched for age and educational level were investigated by means of neuropsychological tests (MoCa, MMSE, FAB), psychiatric scales (BDI, PBA) and motor evaluation (UHDRS). Blood samples were collected to investigate BDNF platelet levels determined by ELISA. Results HD patients showed statistically significant lower performances at MoCa (p Conclusions Our finding of a lack of significant difference in platelet BDNF between HD and controls could suggest along with recent studies on human blood that peripheral levels of BDNF are not informative as HD biomarkers. However, the correlation between BDNF platelet levels and disease duration might indicate that the peripheral BDNF levels can fluctuate in different phases of the disease.

Increasing evidence supports a role for oxidative DNA damage and impaired DNA repair mechanisms in the pathogenesis of age related neurodegenerative diseases. Within this context there is a current interest in the understanding of the role played by polymorphisms of DNA repair genes in the inter-individual risk to develop neurodegenerative pathologies, as well as in the onset and the progression of disease symptoms. Particularly, somatic CAG repeat expansion of the gene encoding for huntingtin has been observed in tissues of patients affected by Huntington's disease (HD), including blood and brain. Recent evidence suggests that somatic CAG repeat expansion in HD cells might contribute to disease age at onset and is mediated by the DNA repair OGG1 enzyme, during the removal of 8-oxoguanine (8-oxoG) from the DNA. There is also evidence that the expression of hMTH1, which removes 8-oxoG from the nucleotide pool, protects mice from HD-like symptoms, and progenitor striatal cells from the toxic effects of the mutant huntingtin. The hOGG1 Ser326Cys polymorphism results in reduced OGG1 activity and increased 8-oxoG formation. In the present study, performed on blood DNA from 91 HD subjects, we observed that bearers of the mutant Cys326 allele (Ser326Cys + Cys326Cys) tend to have an increased number of CAG repeats of the expanded HD allele (P = 0.049); moreover bearers of at least one copy of the mutant Cys326 allele, mainly heterozygous subjects, showed a significant (P = 0.041) earlier disease onset than Ser326Ser wild-type individuals, suggesting a possible role of the hOGG1 Ser326Cys polymorphism in HD phenotype.

Background Impaired social behaviour, partly related to altered perception of emotions, is commonly reported in HD patients. Over the past few years the role of oxytocin (OT) as social hormone has been proposed and it is supported by the improvement of recognition of the expression of the faces after administration of intranasal OT. Aims To investigate social cognition in HD and to evaluate the role of OT as social hormone. Methods 8 symptomatic HD (stage II S&F) and 9 controls, matched for age and educational level were investigated for social cognition by means of an extensive battery of neuropsychological tests. The basal levels of OT were analysed in the whole study group and searching for relationship between blood levels and social cognition. Results HD patients showed lower performances at Faux pas, Strange Stories test and in recognising face expression evaluated by KDEF scale (p Conclusions The present study, albeit severely limited by sample size, shows an extensive impairment of social cognition in HD population. The impairment mainly involves the perception of emotions, dependent both on the cognitive impairment and on basal levels of OT. Our finding that social cognition, at least as regards to perception of emotions, may be in part related to OT might support the hypothesis of hypothalamic involvement in HD.

We investigated the striatal and extrastriatal DAT availability (SPM8) by [123I]FP-CIT-SPECT in 15 PD patients with depression and 35 PD patients without depression. A cluster with significant (p < 0.05) lower tracer binding in PD with depression was found in left cingulate cortex, persistent after correction for age, disease severity and duration, and inversely correlated with depression scores (r −0.336, p < 0.05). Our data indicate a significant association between PD depression and cingulate dopaminergic denervation supporting the dopaminergic hypothesis of PD depression.

In this work we analysed, by immunohistochemistry, a series of brain tumors to detect the levels and cellular distribution of Hsp60 and Hsp70. We found that Hsp60 levels were significantly higher than those of Hsp70 in neuroepithelial tumors, while levels of both molecules were not significantly different from each other in meningeal neoplasms. In particular, Hsp60 immunopositivity was present mainly at the cytoplasmic level, while Hsp70 immunopositivity was found both in the cytoplasm and in the nucleus of tumor cells. The levels of these molecules in healthy control cells were always very low. Finally, Hsp60 and Hsp70 levels did not correlate with the different types (WHO grade) of neoplasm. Our results are partially in agreement with previous studies and suggest that Hsp60 is not increased by a passive phenomenon (e.g., due to the stress caused by the peritumor environment on cancer cells) but may be actively implicated in tumor progression, e.g. inhibiting tumor cell death or antitumor immune system response, as already postulated in vitro. We also briefly discuss the most recent publications on the extramitochondrial localization of Hsp60 in tumor cells and its role in tumor progression.

Background Wegener Granulomatosis (WG) and psoriasis are two rheumatologic diseases in which neurological involvement is quite rare. Case history A 72-years-old male, diagnosis of WG since 1999. Since 2003 he presented simple verbal tics, four limbs involuntary movements. The cognitive profile was in line with an amnestic mild cognitive impairment. Hyperkinetic syndrome improved with low dosages of Tetrabenazine. A 67-years-old woman presented with choreic movements mainly at the left limbs and painful swelling left wrist. Neuropsychological evaluation showed a mild frontal dysfunction. Within 4 months diagnosis of psoriasis was made. Methylprednisolone was given with improvement of chorea, instead tetrabenazine was stopped for parkinsonism. Genetic tests for HD, HDL2, SCA-17 and research for acanthocytis were negative. FDG-PET showed right caudo-putaminal hypermetabolism in the first patient and bilateral basal ganglia hypermetabolism in the second patient. Brain MRI didn9t show any significant alteration in both patients. CSF examination, iron and cupper sieric values were in the normal range. Sieric anti-basal ganglia antibodies (ABGA) showed auto-antigen of 45 kDa. Conclusions ABGA positivity has been described during autoimmune diseases such as Sydenham Chorea, ADEM and PANDAS‏ and post-mortem studies showed perivascular infiltration by lymphocytes in the basal ganglia. Striatal hypermetabolism on FDG-PET with chorea associated with SLE and primary antiphospholipid syndrome has been reported probably (1,2) due to autoantibodies vs basal ganglia neurons. The ABGA positivity does not imply a pathogenetic relationship, however the concomitant striatal hypermetabolism in our cases could extend the spectrum of chorea associated with autoimmune diseases.

Background Huntington9s disease (HD) is characterised by involuntary movements, cognitive decline and psychiatric symptoms such as aggressiveness, and depression. In most cases involuntary movements and psychiatric symptoms are controlled by antipsychotic drugs, but sometimes side effects as parkinsonism or worsening of depression and apathy can reduce the therapeutic window of these drugs. Aims To evaluate the beneficial effect of Valproic Acid on psychiatric symptoms such as agitation and aggressiveness as well as depression in HD. Methods 10 symptomatic genetically confirmed HD patients (mean CAG repeat 40±2), mean disease duration (8±2 years) on antipsychotics, all with aggressiveness defined as disabling by the patients along with the care giver, were included in an open unblinded trial. Clinical evaluation including motor (UHDRS), psychiatric (NPI) and cognitive scales (MMSE) was performed at baseline and after 6 and 12 months of Valproic Acid (from 300 up to 1000 mg die). Results In our cases we reported a reduction of 10 points of NPI score in each patient persisting 1 year after the introduction of Valproate without any side effect reported. Conclusions The beneficial effect of Valproic Acid on aggressive patients is well documented since 19971 and, to our knowledge, there are only two case reports2 3 that support this effect in such psychiatric disturbance in HD. However no systematic study was done so far in this topic. Moreover, the successful use of Valproic acid in controlling aggressiveness allowed us not to increase the daily dose of neuroleptic, so preventing motor and psychiatric side effects. References 1. Haas S, Vincent K, Holt J, et al. Divalproex: a possible treatment alternative for demented, elderly aggressive patients. Ann Clin Psychiatry 1997;9:145–7. 2. Grove VE Jr, Quintanilla J, DeVaney GT. Improvement of Huntington9s disease with olanzapine and valproate. N Engl J Med 2000;343:973–4. 3. Rask G, Anderson C. Good effect of valproate against aggression in Huntington disease. Only two cases reported earlier. Lakartidningen 2010;107:3060–1.

Background Huntington9s disease (HD) is pathologically characterised by a selective neurodegeneration of vulnerable populations of neurons, with an early marked neuronal loss and atrophy in the neostriatum. Dopaminergic innervations of neostriatal neurons originate in the substantia nigra pars compacta. Few studies have investigated the neuronal loss and the functional role of the substantia nigra in HD. Neuropathological and neurochemical studies provide conflicting results, with the evidence of neuronal loss varying from minimal loss to 40%. The few imaging studies evidenced a reduction of striatal DAT uptake and vescicular monoamine transporter type-2 (VMAT2). No correlations with clinical data have yet been investigated. Aims We have evaluated in vivo the integrity of nigrostriatal projections in genetically confirmed HD patients and determined whether their clinical and neuropsychiatric features are correlated with the dopamine transporter (DAT) levels. Methods 12 HD patients and 12 controls, age matched, underwent SPECT scans with 123I-FP-CIT, a tracer that selectively binds to DAT, following an adequate drug washout. The association between clinical aspects (age of onset, duration and severity of disease, mean number of triplets, severity of involuntary movements and bradykinesia), neuropsychological assessment (verbal and visuospatial memory, attentive, executive and abstractive capacities), neuropsychiatric features (NeuroPsychiatry Inventory Scale) and striatal DAT uptake (ROI approach analysis) was explored. Results Striatal (p Conclusions Reduced striatal DAT binding suggests nigrostriatal pathology in HD that could be related to substantia nigra degeneration. The absence of any correlation with age of onset, disease duration and severity and the number of triplets suggests that nigrostriatal pathology occurs early in the course of the disease. Also, the lack of any kind of correlation between clinical, neuropsychological and neuropsychiatric features with striatal DAT uptake suggests that motor and both psychiatric and cognitive aspects in HD are not related to nigrostriatal degeneration.