Suggestive linkage to chromosome 19 in a large Cuban family with late‐onset Parkinson's disease

The identification of disease genes using family‐based approaches has provided important insights into the pathogenesis of Parkinson's disease (PD) demonstrating the importance of genetic studies on monogenic forms of the disease. We studied a large Cuban family with typical, late‐onset PD and probable autosomal dominant inheritance. Mean age at onset was 61.2 years (±12.53, 45–76). Other phenotypes such as essential tremor and atypical parkinsonism were observed in this family. We carried out a genome‐wide scan and linkage analyses. The genetic data were analyzed using a conservative model in which only patients with clinically definite or likely PD were considered affected, other phenotypes were regarded as “unknown.” Multipoint analyses yielded a maximum LOD of 2.26 between markers D19S221 and D19S840. Haplotype analysis showed a region on chromosome 19 shared by six of seven PD patients. The essential tremor phenotype and the atypical parkinsonism do not segregate with this haplotype, suggesting a different etiology. Our findings suggest the presence of a novel locus for PD on chromosome 19p13.3–q12. We propose that an oligogenic model with moderate contribution of two or three genes rather than a “pure” monogenic model might explain better the wide range in age at onset, the reduced penetrance and the phenotypical variability observed in PD families. © 2003 Movement Disorder Society     

Lack of association between IL-1β, TNF-α, and IL-10 gene polymorphisms and sporadic Parkinson's disease in an Italian cohort

Pascale E, Passarelli E, Purcaro C, Vestri AR, Fakeri A, Guglielmi R, Passarelli F, Meco G. Lack of association between IL‐1β, TNF‐α, and IL‐10 gene polymorphisms and sporadic Parkinson’s disease in an Italian cohort.
Acta Neurol Scand: 2011: 124: 176–181.
© 2010 John Wiley & Sons A/S. Objective – There is increasing evidence suggesting that neuroinflammation and microglia activation may play important roles in the pathway leading to neuronal cell death in Parkinson’s disease (PD). Chronic activation of microglia may cause neuronal damage through the release of potentially cytotoxic molecules, such as pro‐inflammatory cytokines. Different functional promoter polymorphisms within genes coding pro‐ or anti‐inflammatory cytokines involved in the immune reactions in the brain might influence the risk of developing PD or the age of disease onset. Aim – To investigate the interleukin (IL)‐1β‐511, tumor necrosis factor alpha (TNF‐α)‐308, and interleukin (IL)‐10‐1082 gene polymorphisms as susceptibility factors for PD. Methods;– We analyzed genotype and allele distributions of these polymorphisms in146 Italian patients with PD and 156 healthy controls. Results – None of the polymorphisms we investigated was found to be associated with PD or with age of disease onset. No significant differences between patients with PD and controls were found as regards the concomitant presence of variant alleles in the three polymorphisms studied. We found that only the combined genotype TNF‐α‐308GG/IL‐1β‐511T(+) is associated with a decreased risk of PD. Conclusion – Our results indicate that the cytokine gene polymorphisms we investigated are not related to the development of PD in the Italian population; further studies are warranted to clarify the role of the TNF‐α‐308GG/IL‐1β‐511T(+) combined genotype.     

α-突触核蛋白及其在帕金森病发病中的可能机制

α-突触核蛋白（AS）足Lewy体的重要组成成分。AS基因定位于第4号染色体，其突变型与常染色体显性遗传性帕金森病（PD）的发病密切相关。在PD中，AS出现了折叠错误和排列混乱。AS的聚集能力，特别是在氧化应激状态下，被认为是其病理机制的核心，AS的异常聚集和降解障碍导致蛋白酶的抑制和多巴胺能神经元的死亡。因此，AS致病形式对认识PD的发生有重要意义。     

Activities of daily living and quality of life in persons with newly diagnosed Parkinson’s disease according to subtype of disease,and in comparison to healthy controls

Hariz G‐M, Forsgren L. Activities of daily living and quality of life in persons with newly diagnosed Parkinson’s disease according to subtype of disease, and in comparison to healthy controls.
Acta Neurol Scand: 2011: 123: 20–27.
© 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard. Objective – To describe activity of daily living (ADL) and quality of life (QoL) at first visit to a neurological centre, in patients subsequently diagnosed with Parkinson’s disease (PD), according to subtype of disease and compared to healthy controls. Materials and methods – 99 patients and 31 controls were included. Patients were classified into three groups according to predominant symptoms: 50 Postural instability‐gait difficulties (PIGD), 37 tremor dominant, 12 indeterminate. Evaluations included ADL‐taxonomy, SF‐36, and the Parkinson disease questionnaire (PDQ‐39). Results – Patients experienced early on limitations in ADL and QoL compared to controls. Patients with PIGD subtype had already at first visit a worse status, clinically and in ADL and QoL, than patients with tremor dominant type. Conclusions – Already at first visit to a neurological centre, patients who will eventually receive the diagnosis of PD exhibited restrictions in ADL and QoL. Patients with axial symptoms were affected most.     

The role of APOE alleles in incident Parkinson’s disease. The Norwegian ParkWest Study

Vefring H, Haugarvoll K, Tysnes O‐B, Larsen JP, Kurz MW, for the Norwegian ParkWest Study group. The role of APOE alleles in incident Parkinson’s disease. The Norwegian ParkWest Study.
Acta Neurol Scand: 2010: 122: 438–441.
© 2010 John Wiley & Sons A/S. Objectives – Apolipoprotein E (APOE) gene alleles have been associated with various neurodegenerative disorders. However, there have been conflicting reports on associations between APOE alleles and Parkinson’s disease (PD) and age at onset in PD. There exist no data on APOE alleles in an unselected cohort of patients with incident PD. Patients and methods – To determine the role of APOE alleles in PD and age of onset in PD at time of diagnosis, 203 patients with incident PD and 187 healthy control subjects from Western and Southern Norway were investigated according to their APOE allele status. Results – No association was observed between any APOE alleles and susceptibility to PD or age at onset in PD. Conclusion – In our cohort of unselected, incident PD patients APOE alleles do not seem to play a role for development of PD. Prospective, long‐term follow‐up may still reveal associations between APOE alleles and clinical and neuropsychological progression in PD.     

Transcranial brain sonography findings in discriminating between parkinsonism and idiopathic Parkinson disease

BACKGROUND: In several pilot studies, transcranial brain sonography findings of substantia nigra and lenticular nucleus discriminated between idiopathic Parkinson disease (PD) and atypical parkinsonian disorders. OBJECTIVE: To study the use of transcranial brain sonography in excluding the diagnosis of idiopathic PD in patients with sporadic parkinsonism. DESIGN AND SETTING: All patients with parkinsonism admitted to our movement disorder clinic from January 1, 2003, through December 31, 2005, who fulfilled clinical diagnostic criteria for definite PD, probable parkinsonian variant of multiple-system atrophy (MSA-P), or probable progressive supranuclear palsy (PSP) were prospectively studied with transcranial brain sonography by an investigator blinded to clinical diagnoses. Patients Eligible patients included 138 with sporadic idiopathic PD (82 men and 56 women; mean +/- SD age, 67.1 +/- 9.8 years; mean +/- SD disease duration, 7.5 +/- 6.3 years; mean +/- SD motor score on the Unified Parkinson Disease Rating Scale, 32.6 +/- 18.1), 21 with MSA-P (10 men and 11 women; mean +/- SD age, 65.4 +/- 9.5 years; mean +/- SD duration of disease, 3.1 +/- 2.0 years; mean +/- SD motor score, 33.5 +/- 16.1), and 22 with PSP (13 men and 9 women; mean +/- SD age, 71.2 +/- 5.5 years; mean +/- SD duration of disease, 3.4 +/- 2.4 years; mean +/- SD motor score, 46.2 +/- 18.9). In 7 patients, transcranial brain sonography was not possible owing to insufficient temporal acoustic bone windows. MAIN OUTCOME MEASURES: Sensitivity, specificity, and predictive value of transcranial brain sonography in indicating an atypical parkinsonian syndrome rather than idiopathic PD in patients with sporadic parkinsonism. RESULTS: Normal echogenic substantia nigra indicated MSA-P rather than PD (sensitivity, 90%; specificity, 98%; positive predictive value, 86%), whereas third-ventricle dilatation of more than 10 mm in combination with lenticular nucleus hyperechogenicity indicated PSP rather than PD (sensitivity, 84%; specificity, 98%; positive predictive value, 89%). Normal echogenic substantia nigra combined with lenticular nucleus hyperechogenicity indicated MSA-P or PSP (sensitivity, 59%; specificity, 100%; positive predictive value, 100%). In parkinsonism with age at onset younger than 60 years, normal echogenic substantia nigra alone indicated MSA-P or PSP (sensitivity, 75%; specificity, 100%; positive predictive value, 100%). CONCLUSIONS: Distinct transcranial brain sonography findings can exclude the diagnosis of PD in patients with sporadic parkinsonism. Sonographic discrimination of atypical parkinsonian syndromes from PD is clearer in patients with onset of parkinsonism at younger than 60 years.     

Clinical and genetic evaluation of 8 Polish families with levodopa-responsive parkinsonism

Summary. We studied 8 large Polish families with parkinsonism, 6 of which were newly identified. Thirty-six family members had well-documented levodopa-responsive parkinsonism. The phenotype of affected individuals was indistinguishable from that of persons with idiopathic Parkinson disease (PD). The pattern of inheritance in 5 families was consistent with autosomal dominant transmission; in 3 families the mode of inheritance was uncertain. Single photon emission computed tomography (SPECT) studies with the dopamine transporter radioligand [¹²³I]FP-CIT were performed in 1 family. The SPECT study showed striatal presynaptic dopaminergic degeneration consistent with sporadic PD in 1 affected family member and no signs of nigrostriatal dopaminergic dysfunction in 5 at-risk individuals. Sequence analysis in all 8 families excluded known genes associated with familial parkinsonism. Genome-wide 2-point linkage studies in the largest 2 families did not identify significant linkage (z > 3.0), although positive scores were obtained for 5q23 (D5S1462 and D5S2501), a locus previously implicated in disease susceptibility.     

SCA14 in Norway, two families with autosomal dominant cerebellar ataxia and a novel mutation in the PRKCG gene

Koht J, Stevanin G, Durr A, Mundwiller E, Brice A, Tallaksen CME. SCA14 in Norway, two families with autosomal dominant cerebellar ataxia and a novel mutation in the PRKCG gene.
Acta Neurol Scand: 2012: 125: 116–122.
© 2011 John Wiley & Sons A/S. Objectives – Despite a similar prevalence of autosomal dominant cerebellar ataxia (ADCA) in Norway compared to other European countries, less than 10% of the families are explained by the CAG trinucleotide expansions. We wanted to find the occurence of SCA14 in the dominant ataxia population and describe the phenotype. Methods – We screened a large dominant cerebellar ataxia cohort for mutations in the PRKCG gene. Patients were evaluated according to a standard clinical protocol for ataxia patients. Results – A novel mutation was found in two families, a C to A transversion altering Histidine to a Glutamine at codon 139, located in a highly concerved region in the gene. It completely co‐segregated with the affected family members and was not seen in 576 control chromosomes. Genetic analysis revealed common alleles at three microsatellite markers between these two families suggesting a shared ancestral chromosome. Affected subjects displayed a mild, slowly progressive cerebellar syndrome that included gait and limb ataxia and saccadic pursuit and head tremor in one. Age at onset ranged from 10 to 45 years. Conclusions – These are the first families with SCA14 reported from Scandinavia and a new mutation in the PRKCG gene. The occurrence in the Norwegian dominant ataxia cohort is 3.5%.     

Parkinson‐related genetics in patients treated with deep brain stimulation

Johansen KK, Jørgensen JV, White LR, Farrer MJ, Aasly JO. Parkinson‐related genetics in patients treated with deep brain stimulation.
Acta Neurol Scand: 2011: 123: 201–206.
© 2010 John Wiley & Sons A/S. Objectives – To analyze the frequency of mutations associated with Parkinson’s disease (PD) in a general PD population compared to patients with PD selected for deep brain stimulation (DBS) and evaluate the outcome of surgery. Material and methods – A total of 630 consecutive patients with PD were genetically screened, and 60 had DBS surgery, 37 subthalamic nucleus (STN), 21 ventrointermediate nucleus of thalamus (VIM), and two globus pallidus internus (GPi). Results – Mutations in LRRK2, PRKN, and PINK1 were found: the first two of these being overrepresented in STN‐operated patients, but none being found in VIM‐operated patients. Clinical outcome of the surgery was similar in patients with mutations compared to those without. Conclusions – In a consecutive PD population, patients treated with STN‐DBS are overrepresented for PD‐related mutations and they seem to benefit from DBS as well as patients without mutations.     

Leptin and ghrelin concentrations and weight loss in Parkinson’s disease

Fiszer U, Micha?owska M, Baranowska B, Wolińska‐Witort E, Jeske W, Jethon M, Pia?cik‐Gromada M, Marcinowska‐Suchowierska E. Leptin and ghrelin concentrations and weight loss in Parkinson’s disease.
Acta Neurol Scand: 2010: 121: 230–236.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objectives – To investigate the role of leptin, ghrelin, GH and IGF‐1 in energy balance disturbances in Parkinson’s disease (PD). Materials and methods – Thirty‐nine patients were included: 11 PD patients with unintentional weight loss, 16 PD patients without weight loss and 12 controls. UPDRS, MMSE, MADRS, appetite scale, BMI, adipose tissue content, plasma leptin and active ghrelin concentrations and serum GH, IGF‐1, TSH, T3 and T4, concentrations were evaluated. Results – A lower plasma leptin concentration and a higher serum IGF‐1 concentration were found in PD patients with weight loss. BMI and the content of adipose tissue were positively correlated with leptin concentration in all PD patients. Paradoxically, the lower BMI was, the lower plasma active ghrelin concentration was in PD patients with the weight loss. Conclusion – These findings confirm that changes of plasma leptin concentration occur in PD patients with loss of weight.     

Creutzfeldt–Jakob disease with PRNP G114V mutation in a Chinese family

Liu Z, Jia L, Piao Y, Lu D, Wang F, Lv H, Lu Y, Jia J. Creutzfeldt–Jakob disease with PRNP G114V mutation in a Chinese family.
Acta Neurol Scand: 2010: 121: 377–383.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Background – Recent evidence has shown clinical phenotypic heterogeneity of inherited prion diseases, even between patients harbouring the same mutation in the PRNP gene. Objective and methods – We collected clinical data from a Chinese family with autosomal dominant dementia and screened the PRNP gene on 28 living members. A stereotactic biopsy of the right frontal lobe of the proband was performed. Results – The family comprised four affected individuals within two successive generations. The age of onset was in 30 or 40 s, and the duration was about 2–3 years. Clinical features of the affected members included neuropsychiatric disturbances, progressive dementia and extrapyramidal symptoms. Immunostaining for prion protein showed fine granular deposits of PrP^sc in the neuropil. The PRNP gene analysis demonstrated a heterozygous G114V mutation in 15 family members. The proband was diagnosed as familial Creutzfeldt–Jakob disease (fCJD). Conclusion – This study strengthens the linkage of the G114V mutation to CJD. It supports the worldwide distribution of fCJD despite differences in genetic background.     

Distinguishing Parkinson's disease and essential tremor with transcranial sonography

Objectives – Until today there is no reliable test that can clearly distinguish Parkinson’s disease (PD) from the essential tremor (ET). Our aim was to determine the usefulness of the transcranial sonography (TCS) in the differential diagnosis of the PD and ET as well as the interobserver reliability for this method. Methods – Transcranial sonography of substantia nigra and clinical examination were performed on 80 PD patients, 30 ET patients, and 80 matched controls by two independent physicians. Results – Bilateral SN hyperechogenicity over the margin of 0.20 cm² was found in 91% of PD patients, 10% of healthy subjects, and in 13% patients with ET. Interobserver agreement for this method was significant (Student’s t‐test, P = 1.000). Conclusions – Substantia nigra hyperechogenicity on TCS is a highly specific finding of PD, where in healthy individuals or in ET patients, it might correspond to an increased risk of developing PD later in life or might also be because of the impairment of nearby area of nucleus ruber in ET patients, as suggested by positron emission tomography studies. TCS may serve as a practical and sufficiently sensitive neuroimaging tool in PD diagnoses and in distinguishing it from ET; its repeatability and accuracy might add to its practical value.     

Interleukin-2 gene expression in different phases of episodic cluster headache--a pilot study

Kummer A, Scalzo P, Cardoso F, Teixeira AL. Evaluation of fatigue in Parkinson’s disease using the Brazilian version of Parkinson’s Fatigue Scale.
Acta Neurol Scand: 2011: 123: 130–136.
© 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard. Objective – Fatigue is common in Parkinson’s disease (PD). However, factors associated with fatigue in PD are still controversial. This study aimed to translate the Parkinson’s Fatigue Scale (PFS) into Brazilian‐Portuguese, to test its psychometric properties, and to assess the severity of fatigue in PD as well as its relation to demographic and clinical features, depression, anxiety, excessive daytime sleepiness and cognitive performance. Methods – We translated and assessed the internal consistency of the Brazilian version of the PFS. After, we assessed 87 PD patients with several neurological and psychopathological instruments. Results – The Brazilian version of PFS had good internal consistency (Cronbach’s alpha = 0.939). Clinical significant fatigue was present in 36 patients (41.4%). A logistic regression analysis showed that fatigue was better explained by dysthymia (P = 0.006), more severe symptoms of depression as assessed by the Hamilton Depression Rating Scale (P = 0.027), daytime sleepiness (P = 0.022) and female gender (P = 0.031). Conclusions – Fatigue is a common non‐motor symptom in PD and seems to be associated with female gender, dysthymia, severity of depression and daily somnolence.     

Serum somatostatin in early‐stage Parkinson’s disease

Shiraishi M, Kobayashi T, Watanabe H, Kamo T, Hasegawa Y. Serum somatostatin in early‐stage Parkinson’s disease.
Acta Neurol Scand: 2010: 121: 225–229.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objective – To compare levels of plasma digestive hormones in patients with and without nausea or vomiting during initial treatment of early‐stage Parkinson’s disease (PD). Methods – This was a 3‐week, open‐label, randomized study of treatment with an antiparkinson drug in untreated PD patients. We measured the levels of plasma digestive hormones before (baseline) and 3 weeks after administration of an antiparkinson drug. Results – Mean value of serum somatostatin at baseline was significantly increased in PD patients compared with the control group (P < 0.01). Serum somatostatin levels were significantly increased after treatment in subjects who experienced nausea or vomiting (P < 0.01). However, significant increase in serum somatostatin levels after treatment was not observed in PD patients without nausea or vomitting. Conclusion – Serum somatostatin in early‐stage PD patients before treatment was increased compared with healthy subjects. The nausea and vomiting induced by antiparkinson drugs may be related to uncontrolled somatostatin secretion through central vagus nerve dysfunction .     

Recurrent falls and mortality in Parkinson’s disease: a prospective two‐year follow‐up study

Matinolli M, Korpelainen JT, Sotaniemi KA, Myllylä VV, Korpelainen R. Recurrent falls and mortality in Parkinson’s disease: a prospective two‐year follow‐up study.
Acta Neurol Scand: 2011: 123: 193–200.
© 2010 John Wiley & Sons A/S. Objectives – To evaluate the risk factors for recurrent falling and mortality in Parkinson’s disease (PD) in a prospective study design. Materials and methods – One hundred and twenty‐five PD patients were included in the study. Baseline medical data were collected, and patients were clinically tested for mobility and balance. Falls were prospectively recorded for 2 years. Mortality was documented 4 years after the baseline. Results – Seventy‐nine patients reported altogether 3125 falls during the follow‐up, and 59 patients were classified as recurrent fallers. Altogether 126 fall injuries including six fractures were reported. Eighteen patients had died by the time of the hospital chart review. History of falling (OR 3.02, 95% CI 1.23–7.44) and the Unified Parkinson’s Disease Rating Scale activities of daily living score (OR 1.13, 95% CI 1.04–1.22) were independent risk factors for recurrent falling in PD, whereas slow walking speed (OR 16.28, 95% CI 1.85–142.97) was an independent risk factor for mortality in PD. Conclusions – History of falling and disease severity indicate increased risk of recurrent falls in PD, while patients with slow walking speed may have an increased risk of mortality. Recurrent falling was not associated with increased risk of mortality in PD in this study.     

Serum heme oxygenase‐1 levels are increased in Parkinson’s disease but not in Alzheimer’s disease

Mateo I, Infante J, Sánchez‐Juan P, García‐Gorostiaga I, Rodríguez‐Rodríguez E, Vázquez‐Higuera JL, Berciano J, Combarros O. Serum heme oxygenase‐1 levels are increased in Parkinson’s disease but not in Alzheimer’s disease.
Acta Neurol Scand: 2010: 121: 136–138.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objective – Oxidative stress is implicated in Parkinson’s disease (PD) and Alzheimer’s disease (AD), and heme oxygenase‐1 (HO‐1) is a potent antioxidant overexpressed in PD substantia nigra and AD cerebral cortex and hippocampus, indicating a possible up‐regulation of antioxidant defenses in both neurodegenerative diseases. The role of HO‐1 in peripheral blood of PD and AD patients remains unresolved. Methods – We measured serum HO‐1 levels in 107 patients with PD, 105 patients with AD, 104 controls for PD and 120 controls for AD. Results – The median serum concentration of HO‐1 was significantly higher in PD patients (2.04 ng/ml) compared with that of PD controls (1.69 ng/ml, P = 0.016), with PD patients predominating over controls in the upper tertile of serum HO‐1 levels, whereas there was more PD controls than PD patients in the lower tertile (P = 0.006). Median serum levels of HO‐1 did not differ significantly between AD patients and AD controls. Conclusion – The increase of serum HO‐1 levels in PD patients could indicate a systemic antioxidant reaction related to a chronic oxidative stress state in PD brain.     

Five‐year follow‐up of substantia nigra echogenicity in idiopathic REM sleep behavior disorder

Hyperechogenicity of the substantia nigra visualized by transcranial sonography occurs in most Parkinson's disease (PD) patients. Idiopathic rapid eye movement (REM) sleep behavior disorder (IRBD) subjects eventually develop PD and other synucleinopathies. This study was undertaken to evaluate whether in IRBD, transcranial sonography identifies subjects who convert to PD and other synucleinopathies, and whether substantia nigra echogenic size changes with time. It was a prospective study in which 55 IRBD patients underwent transcranial sonography at baseline and were invited to follow‐up after 5 years. Patients were assessed by the same experienced sonographer who was blinded to clinical data and baseline transcranial sonography results, and used the same equipment and adjustments. Twenty‐one (38.2%) subjects were diagnosed with a synucleinopathy (PD in 11, dementia with Lewy bodies in nine, and multiple system atrophy in one). Sensitivity of baseline substantia nigra hyperechogenicity for the development of a synucleinopathy was 42.1%, specificity 67.7%, positive predictive value 44.4%, negative predictive value 65.6%, and relative risk 1.29. No differences were detected between the first and second examination in mean size of the substantia nigra (0.20 ± 0.09 cm² vs. 0.19 ± 0.07 cm²; P = 0.777) and in percentage of patients with substantia nigra hyperechogenicity (33.3% vs. 42.8%, P = 0.125). Transcranial sonography of the substantia nigra alone is not a useful tool to identify IRBD subjects at risk for the development of PD or a synucleinopathy after 5 years of follow‐up. In IRBD, transcranial sonography cannot be used to monitor the degenerative process in the substantia nigra, because echogenicity size remains stable over time. © 2014 International Parkinson and Movement Disorder Society     

Caregiver distress associated with neuropsychiatric problems in patients with early Parkinson’s disease: the Norwegian ParkWest study

Leiknes I, Tysnes O‐B, Aarsland D, Larsen JP. Caregiver distress associated with neuropsychiatric problems in patients with early Parkinson’s disease: the Norwegian ParkWest study.
Acta Neurol Scand: 2010: 122: 418–424.
© 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard. Objectives – We investigated caregiver distress associated with neuropsychiatric problems in patients with newly diagnosed Parkinson’s disease (PD). Materials and methods – Persons who were next of kins of 198 patients and 168 healthy individuals completed the Neuropsychiatric Inventory Caregiver Distress Scale. Results – Even at the time of diagnosis PD has a considerable impact on the next of kins’ experience of distress. Nearly 50% reported distress, significantly more than in the control group, and more than one‐quarter reported moderate severe distress. Except the more rarely reported neuropsychiatric symptoms, apathy was the symptom that most frequently caused caregiver distress in PD patient’s next of kin (94.5%), followed by depression (88.2%), anxiety (86.2%) and irritability (83.3%). Conclusions – The study underlines the importance of focusing on neuropsychiatric aspects in patients and associated caregiver distress even in early PD management.     

Medication dose reductions after pallidal versus subthalamic stimulation in patients with Parkinson's disease

Evidente VGH, Premkumar AP, Adler CH, Caviness JN, Driver‐Dunckley E, Lyons MK. Medication dose reductions after pallidal versus subthalamic stimulation in patients with Parkinson’s disease.
Acta Neurol Scand: 2011: 124: 211–214.
© 2010 John Wiley & Sons A/S. Objective – To compare the medication dose reduction between deep brain stimulation (DBS) of the globus pallidus interna (GPi) vs subthalamic nucleus (STN) in matched patients with Parkinson’s disease (PD). Materials and methods – Records of 12 patients with PD who underwent GPi‐DBS at our institution from 2002 to 2008 were matched by pre‐operative PD medication doses and pre‐operative motor Unified Parkinson’s Disease Rating Scale (UPDRS) scores to 12 cases of STN‐DBS. PD medication doses were converted to levodopa equivalent doses (LEDs). Results – GPi and STN groups had similar mean pre‐operative LEDs and motor UPDRS scores. At 6 months post‐DBS, there was no significant difference in percent reduction in LEDs between the GPi (47.95%) and STN (37.47%) groups (P = 0.52). The mean post‐operative ‘medication off/stimulation on’ motor UPDRS scores did not differ significantly between GPi (15.33) and STN (16.25) groups (P = 0.74). The mean percent reduction in motor UPDRS scores was also similar between GPi (58.44%) and STN (58.98%) patients (P = 0.94). Conclusions – We conclude that in disease‐matched patients with PD undergoing DBS, both GPi and STN may result in similar reduction in PD medication doses.     

Light subunit of neurofilament triplet protein in the cerebrospinal fluid after subthalamic nucleus stimulation for Parkinson's disease

Constantinescu R, Holmberg B, Rosengren L, Corneliusson O, Johnels B, Zetterberg H. Light subunit of neurofilament triplet protein in the cerebrospinal fluid after subthalamic nucleus stimulation for Parkinson’s disease.
Acta Neurol Scand: 2011: 124: 206–210.
© 2010 John Wiley & Sons A/S. Objectives – Cerebrospinal fluid (CSF) levels of neurofilament triplet protein (NFL), a non‐specific marker of neuronal damage, are normal in Parkinson’s disease (PD) but increased after brain trauma and in several neurological disorders. Using longitudinal CSF‐NFL measurements as an indicator of neuronal damage, this study investigated the impact of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on the brain, directly following the surgical intervention and in chronically treated patients with PD. Materials and methods – CSF‐NFL levels were measured consecutively in eight patients with PD before and after STN‐DBS treatment. Results – CSF‐NFL levels were normal prior to STN‐DBS and increased sharply during the first 2 weeks post‐operatively, but normalized after 12 months or more. Conclusion – The STN‐DBS procedure leads to an acute but limited neuronal damage, as expected. However, normal CSF‐NFL levels at 12 months post‐operatively and beyond suggest the absence of any long‐term neuronal damage caused by long‐term STN‐DBS stimulation.