Predictors of the emergence of apathy after bilateral stimulation of the subthalamic nucleus in patients with Parkinson's disease.

BACKGROUND: Subthalamic nucleus deep brain stimulation (STN-DBS) is a valid therapeutic tool that ameliorates motor symptoms in patients with Parkinson's disease (PD). However, apathy is one of the neuropsychiatric complications that may occur after STN-DBS surgery, and this may adversely influence the quality of life of patients despite significant motor improvement. OBJECTIVE: This study aimed to elucidate preoperative predictive factors for the presence of postoperative apathy in patients treated with STN-DBS. METHODS: Twenty-five consecutive PD patients receiving bilateral STN-DBS were recruited. The assessment instruments include modified Hoehn & Yahr stages, Unified Parkinson's Disease Rating Scale motor (part III) and dyskinesia (part IVa) scores, Parkinson's Disease Questionnaire-39 scores, Self-Rating Depression Scale scores, and Apathy Scale scores. Predictive factors for postoperative apathy were assessed. RESULTS: While STN-DBS resulted in a significant improvement in motor symptoms, six patients (24%) developed significant apathy after surgery. In multiple logistic regression analyses, preoperative severity of dyskinesia was found to be an independent predictor for the acute phase of postoperative apathy with STN-DBS (odds ratio = 89.993, p = 0.003). CONCLUSIONS: This study suggests that preoperative dyskinesia may predict postoperative apathy in the acute phase in patients with PD treated with STN-DBS. The pathogenesis of postoperative apathy remains unknown, but in patients with severe dyskinesia before STN-DBS, attention should be given to monitoring for postoperative apathy.

UCHL1 S18Y variant is a risk factor for Parkinson's disease in Japan.

BACKGROUND: A recent meta-analysis on the UCHL1 S18Y variant and Parkinson's disease (PD) showed a significant inverse association between the Y allele and PD; the individual studies included in that meta-analysis, however, have produced conflicting results. We examined the relationship between UCHL1 S18Y single nucleotide polymorphism (SNP) and sporadic PD in Japan. METHODS: Included were 229 cases within 6 years of onset of PD, defined according to the UK PD Society Brain Bank clinical diagnostic criteria. Controls were 357 inpatients and outpatients without neurodegenerative disease. Adjustment was made for sex, age, region of residence, smoking, and caffeine intake. RESULTS: Compared with subjects with the CC or CA genotype of UCHL1 S18Y SNP, those with the AA genotype had a significantly increased risk of sporadic PD: the adjusted OR was 1.57 (95 % CI: 1.06 - 2.31). Compared with subjects with the CC or CA genotype of UCHL1 S18Y and the CC or CT genotype of SNCA SNP rs356220, those with the AA genotype of UCHL1 S18Y and the TT genotype of SNP rs356220 had a significantly increased risk of sporadic PD; the interaction, however, was not significant. Our previous investigation found significant inverse relationships between smoking and caffeine intake and PD in this population. There were no significant interactions between UCHL1 S18Y and smoking or caffeine intake affecting sporadic PD. CONCLUSIONS: This study reveals that the UCHL1 S18Y variant is a risk factor for sporadic PD. We could not find evidence for interactions affecting sporadic PD between UCHL1 S18Y and SNCA SNP rs356220, smoking, or caffeine intake.

Multicentre population-based dementia prevalence survey in Japan: a preliminary report.

Community-based surveys were performed in seven rural areas in Japan to investigate the prevalence of dementia and illnesses causing dementia. A total of 5431 elderly subjects were selected based on census data from 1 October 2009. In total, 3394 participants were examined (participation rate: 62.5%), and 768 dementia cases and 529 mild cognitive impairment cases were identified. Of the illnesses causing dementia, Alzheimer's disease was the most frequent (67.4%), followed by vascular dementia (18.9%), dementia with Lewy body disease (4.6%), mixed dementia (4.2%) and other illnesses. The prevalence of dementia according to 5-year age strata between 65 and 99 years was 5.8-77.7% among the participants. The prevalence of dementia in this study was higher than in previous reports in Japan and other countries. To verify the upward trend of dementia prevalence and its background factors, we have scheduled surveys for three other urban areas in 2011-2012.

APOE and CYP2E1 polymorphisms, alcohol consumption, and Parkinson's disease in a Japanese population.

Apolipoprotein E (APOE) is associated with increased oxidative stress, which is caused by reactive oxygen species (ROS). Enhanced cytochrome P450 2E1 (CYP2E1) activity may also increase formation of neurotoxins such as ROS. As Parkinson's disease (PD) is a neurodegenerative disorder, both the APOE and CYP2E1 genes that are involved in neurodegeneration by oxidative stress may be associated with PD risk. We investigated the relationship of the APOE and CYP2E1 rs2864987 polymorphisms and PD risk with special attention to the interaction with alcohol consumption among 238 patients with PD and 296 controls in a Japanese population. The frequencies of the ɛ2, ɛ3, and ɛ4 alleles of the APOE polymorphism among controls were 3.72, 86.7, and 9.63%, respectively. As compared with the APOE ε3/ε3 genotype, the 2/ε4 genotype was associated with an increased risk of PD (adjusted odds ratio (OR) = 9.50, 95% (confidence interval) CI = 1.12-80.6). The presence of the ε3 allele was associated with a decreased risk of PD. Meanwhile, CYP2E1 rs2864987 was not associated with PD risk. Although CYP2E1 is involved in the metabolism of alcohol, there was no evidence of interaction between alcohol consumption and CYP2E1 rs2864987. Our results suggested that the APOE polymorphism might play an important role in PD susceptibility in our Japanese population. Future studies involving larger control and case populations and better alcohol consumption histories will undoubtedly lead to a more thorough understanding of the role of polymorphisms of genes related to the generation of ROS in PD development.

Occupational risk factors for Parkinson's disease: a case-control study in Japan.

BACKGROUND: The evidence for associations between occupational factors and the risk of Parkinson's disease (PD) is inconsistent. We assessed the risk of PD associated with various occupational factors in Japan. METHODS: We examined 249 cases within 6 years of onset of PD. Control subjects were 369 inpatients and outpatients without neurodegenerative disease. Information on occupational factors was obtained from a self-administered questionnaire. Relative risks of PD were estimated using odds ratios (ORs) and 95% confidence intervals (CIs) based on logistic regression. Adjustments were made for gender, age, region of residence, educational level, and pack-years of smoking. RESULTS: Working in a professional or technical occupation tended to be inversely related to the risk of PD: adjusted OR was 0.59 (95% CI: 0.32-1.06, P = 0.08). According to a stratified analysis by gender, the decreased risk of PD for persons in professional or technical occupations was statistically significant only for men. Adjusted ORs for a professional or technical occupation among men and women were 0.22 (95% CI: 0.06-0.67) and 0.99 (0.47-2.07), respectively, and significant interaction was observed (P = 0.048 for homogeneity of OR). In contrast, risk estimates for protective service occupations and transport or communications were increased, although the results were not statistically significant: adjusted ORs were 2.73 (95% CI: 0.56-14.86) and 1.74 (95% CI: 0.65-4.74), respectively. No statistical significance was seen in data concerning exposure to occupational agents and the risk of PD, although roughly a 2-fold increase in OR was observed for workers exposed to stone or sand. CONCLUSION: The results of our study suggest that occupational factors do not play a substantial etiologic role in this population. However, among men, professional or technical occupations may decrease the risk of PD.

Genetic polymorphisms involved in dopaminergic neurotransmission and risk for Parkinson's disease in a Japanese population.

BACKGROUND: Parkinson's disease (PD) is characterized by alterations in dopaminergic neurotransmission. Genetic polymorphisms involved in dopaminergic neurotransmission may influence susceptibility to PD. METHODS: We investigated the relationship of catechol-O-methyltransferase (COMT), monoamine oxidase B (MAOB), dopamine receptor (DR) D2 and DRD4 polymorphisms and PD risk with special attention to the interaction with cigarette smoking among 238 patients with PD and 369 controls in a Japanese population. RESULTS: Subjects with the AA genotype of MAOB rs1799836 showed a significantly increased risk of PD (odds ratio (OR) = 1.70, 95% confidence interval (CI) = 1.12 - 2.58) compared with the AG and GG genotypes combined. The AA genotype of COMT rs4680 was marginally associated with an increased risk of PD (OR = 1.86, 95% CI = 0.98 - 3.50) compared with the GG genotype. The DRD2 rs1800497 and DRD4 rs1800955 polymorphisms showed no association with PD. A COMT -smoking interaction was suggested, with the combined GA and AA genotypes of rs4680 and non-smoking conferring significantly higher risk (OR = 3.97, 95% CI = 2.13 - 7.41) than the AA genotype and a history of smoking (P for interaction = 0.061). No interactions of smoking with other polymorphisms were observed. CONCLUSIONS: The COMT rs4680 and MAOB rs1799836 polymorphisms may increase susceptibility to PD risk among Japanese. Future studies involving larger control and case populations and better pesticide exposure histories will undoubtedly lead to a more thorough understanding of the role of the polymorphisms involved in the dopamine pathway in PD.

[Recurrent syncope due to sick sinus syndrome in a patient with myasthenia gravis associated with thymoma].

We report a 51-year-old man who was admitted to our hospital due to repeated episodes of syncope associated with generalized myasthenic symptoms. Due to myasthenic symptoms with the presence of anti-AchR antoantibody, he was diagnosed as myasthenia gravis (MG) associated with thymoma. However, Holter ECG showed long pause with maximum R-R interval of 3.8 seconds and paroxysmal atrial fibrillation, indicating the diagnosis of sick sinus syndrome. After pace maker implantation and combination therapy with thymomectomy and steroid administration, no arrhythmia in repeated Holter ECG was found. In addition, an anti-kv1.4 antibody was positive in our case. The involvement of cardiomyopathy in patients with MG has been reported, including the association with sudden death. The anti-kv1.4 antibody was recently identified in cases of myasthenia gravis associated with cardiomyositis. After treatments, no arrhythmia was found in our case. Although the cardiomyopathy was not diagnosed in our case because of lacking of histological confirmation, clinical course associated with positive anti-kv1.4 antibody suggested that the cause of syncope might be immune-related cardiomyopathy. To prevent fatal complication of arrhythmia, appropriate examination and therapy against cardiomyopathy associated with myasthenia gravis should be considered.

Novel pathogenic mutations and copy number variations in the VPS13A gene in patients with chorea-acanthocytosis.

Chorea-acanthocytosis (ChAc) is a rare autosomal recessive neurodegenerative disorder caused by loss of function mutations in the vacuolar protein sorting 13 homolog A (VPS13A) gene that encodes chorein. It is characterized by adult-onset chorea, peripheral acanthocytes, and neuropsychiatric symptoms. In the present study, we performed a comprehensive mutation screen, including sequencing and copy number variation (CNV) analysis, of the VPS13A gene in ChAc patients. All 73 exons and flanking regions of VPS13A were sequenced in 35 patients diagnosed with ChAc. To detect CNVs, we also performed real-time quantitative PCR and long-range PCR analyses for the VPS13A gene on patients in whom only a single heterozygous mutation was detected. We identified 36 pathogenic mutations, 20 of which were previously unreported, including two novel CNVs. In addition, we investigated the expression of chorein in 16 patients by Western blotting of erythrocyte ghosts. This demonstrated the complete absence of chorein in patients with pathogenic mutations. This comprehensive screen provides an accurate and useful method for the molecular diagnosis of ChAc.

Dietary intake of folate, vitamin B6, vitamin B12 and riboflavin and risk of Parkinson's disease: a case-control study in Japan.

Increased homocysteine levels might accelerate dopaminergic cell death in Parkinson's disease (PD) through neurotoxic effects; thus, increasing intake of B vitamins involved in the regulation of homocysteine metabolism might decrease the risk of PD through decreasing plasma homocysteine. However, epidemiological evidence for the association of dietary B vitamins with PD is sparse, particularly in non-Western populations. We conducted a hospital-based case-control study in Japan to examine associations between dietary intake of folate, vitamin B6, vitamin B12 and riboflavin and the risk of PD. Patients with PD diagnosed using the UK PD Society Brain Bank criteria (n 249) and controls without neurodegenerative diseases (n 368) were recruited. Dietary intake during the preceding month was assessed at the time of study recruitment using a validated, self-administered, semi-quantitative, comprehensive diet history questionnaire. After adjustment for potential dietary and non-dietary confounding factors, intake of folate, vitamin B12 and riboflavin was not associated with the risk of PD (P for trend = 0.87, 0.70 and 0.11, respectively). However, low intake of vitamin B6 was associated with an increased risk of PD, independent of potential dietary and non-dietary confounders. Multivariate OR (95 % CI) for PD in the first, second, third and fourth quartiles of vitamin B6 were 1 (reference), 0.56 (0.33, 0.94), 0.69 (0.38, 1.25) and 0.48 (0.23, 0.99), respectively (P for trend = 0.10). In conclusion, in the present case-control study in Japan, low intake of vitamin B6, but not of folate, vitamin B12 or riboflavin, was independently associated with an increased risk of PD.

Alcohol drinking and risk of Parkinson's disease: a case-control study in Japan.

BACKGROUND: Although some epidemiologic studies found inverse associations between alcohol drinking and Parkinson's disease (PD), the majority of studies found no such significant associations. Additionally, there is only limited research into the possible interactions of alcohol intake with aldehyde dehydrogenase (ALDH) 2 activity with respect to PD risk. We examined the relationship between alcohol intake and PD among Japanese subjects using data from a case-control study. METHODS: From 214 cases within 6 years of PD onset and 327 controls without neurodegenerative disease, we collected information on "peak", as opposed to average, alcohol drinking frequency and peak drinking amounts during a subject's lifetime. Alcohol flushing status was evaluated via questions, as a means of detecting inactive ALHD2. The multivariate model included adjustments for sex, age, region of residence, smoking, years of education, body mass index, alcohol flushing status, presence of selected medication histories, and several dietary factors. RESULTS: Alcohol intake during peak drinking periods, regardless of frequency or amount, was not associated with PD. However, when we assessed daily ethanol intake separately for each type of alcohol, only Japanese sake (rice wine) was significantly associated with PD (adjusted odds ratio of ≥66.0 g ethanol per day: 3.39, 95% confidence interval: 1.10-11.0, P for trend = 0.001). There was no significant interaction of alcohol intake with flushing status in relation to PD risk. CONCLUSIONS: We did not find significant associations between alcohol intake and PD, except for the daily amount of Japanese sake. Effect modifications by alcohol flushing status were not observed.

[A case of anti-aquaporin 4 antibody-positive Sjögren syndrome associated with a relapsed myelitis in pregnancy].

It is known that pregnancy influences the relapsing rate of multiple sclerosis (MS); however, interaction between pregnancy and relapse of neuromyelitis optica (NMO), a distinct disease from MS, remains unclear. A 34-year-old woman who 1 year previously had clinical history of Sjögren syndrome complicated by myelitis with the presence of anti-AQP4 antibody in her serum, although there was no optic neuritis involvement, was neurologically normal at time of becoming pregnant. In the 22nd week of her pregnancy, however, she developed abdominal belt-shaped numbness and sensory impairment followed by weakness of bilateral lower limb leading to difficulty of her gait. MR imaging revealed hyperintense lesions within the spinal cord extending from C2 to T2 vertebral level with marked spinal cord swelling, indicating relapse of myelitis associated with anti-AQP4 antibody. She was treated with intravenous corticosteroid with marked benefits for her neurological status; she was able to walk without assistance after the treatment. However, in the 30th week she relapsed with myelitis at T2 to T9 vertebral level on MR imaging. Intravenous steroid administration again elicited improvement. She delivered a baby via Caesarean section at 34 weeks of pregnancy. After delivery, she started taking oral corticosteroid as preventive therapy for further relapse of myelitis; thus far she has had no relapse at 7 months of follow-up. There are few reports regarding the influence of pregnancy on anti-AQP4 antibody-positive myelitis. Although further investigation should be done to clarify the difference of immunological changes during pregnancy between NMO and conventional MS, our case together with previous reports indicate increased risk of relapse during pregnancy in NMO. It is necessary to remain vigilant against possible risk of relapse during pregnancy in patients with NMO and/or positive anti-AQP4 antibody. Intravenous steroid administration seems safe and effective against relapse of NMO during pregnancy.

Continuous intraventricular infusion of pentosan polysulfate: clinical trial against prion diseases.

Prion diseases are progressive neurological disorders due to abnormal prion protein (PrP(Sc)) deposition in the central nervous system. At present, there is no effective treatment available for any form of prion disease. Pentosan polysulfate (PPS) has been shown to prolong significantly the incubation period in mice with PrP(Sc) infection when administered to the cerebral ventricles in preclinical trials. In human studies conducted in European countries and Japan, intraventricular PPS was administered to patients with different forms of prion disease and was well tolerated. We report 11 patients with prion disease treated with intraventricular PPS at Fukuoka University from 2004. Cases included three familial CJD (two with V180I mutation, one GSS with P102L mutation), two iatrogenic CJD, and six sporadic CJD cases. At present, average survival period after treatment was 24.2 months (range, 4-49). Seven cases died of sepsis and pneumonia. Subdural effusion with various degrees was seen on CT scan in most cases. Except for these, adverse effects did not occur in the treatment period. Although our preliminary study of the new treatment with PPS by continuous intraventricular infusion showed no apparent improvement of clinical features in patients with prion disease, the possibility of extended survival in some patients receiving long-term PPS was suggested.

ATP-binding cassette transporter G4 is highly expressed in microglia in Alzheimer's brain.

Apolipoprotein E epsilon4 is an independent risk factor for Alzheimer's disease (AD) and is the main constituent of high-density lipoprotein (HDL) as a source of cholesterol in the brain. ATP-binding cassette transporter G4 (ABCG4) is one of the membrane cholesterol transporter which is implicated in HDL-mediated cholesterol efflux, but its precise localization and function in the brain has been unclear. In AD brain, ABCG4 protein was highly expressed in microglial cell that was closely located to senile plaques, whereas in non-neurological cases positive cells were not seen in cortical and nigral tissues. As well as the ABCG4 protein, ABCG4 mRNA signal was detected in microglial cell closely located to senile plaque of AD brain by in situ hybridization histochemistry. These results suggest that upregulated ABCG4 in microglia may accelerate the lipidation of apoE and HDL in the AD brain. This is the first report to show that ABCG4 is highly expressed in microglia on AD brain.

Aseptic meningitis as initial presentation of acute disseminated encephalomyelitis.

BACKGROUND: It is well known that upper respiratory infections or vaccinations are etiologic factors in the majority of acute disseminated encephalomyelitis (ADEM) cases. However, it is less well known that aseptic meningitis may be an initial manifestation of ADEM. OBJECTIVES: To compare the clinical and laboratory findings between aseptic meningitis associated with ADEM (AM-ADEM) and isolated aseptic meningitis (AM-alone), and to determine possible predictive factors for progression to ADEM. METHODS: Twenty-five adults initially diagnosed as having aseptic meningitis were included in the present study. Clinical features, CSF, and laboratory parameters were retrospectively analyzed and compared between those with AM-alone and those who went on to develop AM-ADEM. RESULTS: Twenty patients were diagnosed as AM-alone, whereas five were AM-ADEM. Neurological features associated with ADEM including somnolence, diplopia, ataxia, paresis, and bladder disturbance developed 5-19 days after the first symptoms of aseptic meningitis. Sustained high fever >38 degrees C and hyponatremia <135 mEq/l were seen more frequently in cases with AM-ADEM compared with those with AM-alone. CONCLUSIONS: Patients with an initial diagnosis of aseptic meningitis may develop ADEM during hospitalization. Sustained high fever and hyponatremia upon admission might be useful predictive factors for the subsequent development of ADEM in patients with aseptic meningitis.

Natural killer cells of Parkinson's disease patients are set up for activation: a possible role for innate immunity in the pathogenesis of this disease.

Neuroinflammation in Parkinson's disease (PD) involves activation of microglia, participation of several inflammatory cytokines, prostaglandins, complement and systemic activation of natural killer (NK) cells, suggesting that innate immunity has a role in the pathogenesis of this disease. In this study, we examined NK activity and the expression of its regulatory molecules in peripheral lymphocytes of PD patients and compared the results with those of healthy controls. Expression of the inhibitory NKG2A receptors was significantly lower in PD, causing PD patients to be susceptible in a condition for NK activation after NK cells bind to target cells via these receptors.

The Japanese MCI screen for early detection of Alzheimer's disease and related disorders.

Early detection of Alzheimer's disease and related disorders in Japan is increasingly important. The Mild Cognitive Impairment Screen (MCIS)-derived from the National Institute of Aging CERAD neuropsychologic battery-differentiates normal aging from MCI and mild dementia with 97.3% and 99% accuracy, respectively. The Japanese MCIS (JMCIS), Mini-Mental State Examination (MMSE), quantitative SPECT (qSP), and quantitative MRI (qMRI) were used to classify 63 outpatients at Fukuoka University Hospital who were either normal or had MCI based on Clinical Dementia Rating scores of 0 and 0.5, respectively. Performance statistics for the JMCIS, MMSE, qSP, and qMRI were, respectively: (1) accuracy = 0.964, 0.768, 0.722, 0.733; (2) sensitivity = 0.958, 0.792, 0.688, 0.700; (3) specificity = 1.000, 0.625, 1.000, 1.000; and (4) kappa validity = 0.813, 0.420, 0.296, 0.308. This initial study shows negligible differences between the English and Japanese MCIS, supporting its potential use for early detection in Japan.

Unsaturated fatty acids suppress the expression of the ATP-binding cassette transporter G1 (ABCG1) and ABCA1 genes via an LXR/RXR responsive element.

ATP-binding cassette transporters (ABC) G1 and ABCA1 are membrane cholesterol transporters and have been implicated to mediate cholesterol efflux from cells in the presence of high density lipoproteins and its major protein constituent apolipoprotein A-I, respectively. We previously demonstrated that unsaturated fatty acids suppress the stimulatory effects of oxysterols and retinoids on ABCA1 gene transcription. We here demonstrate that unsaturated fatty acids significantly suppress the stimulatory effects of oxysterols and retinoids on the expression of ABCG1 mRNA and protein and the activity of the wild-type human ABCG1 promoter as well as ABCA1. Mutation or deletion of the DR4 element within the ABCG1 or ABCA1 promoters, to which the transcriptional inducers LXR and RXR bind, abolished the suppressive effects of unsaturated fatty acids. Our observations provide the first evidence that unsaturated fatty acids suppress ABCG1 gene expression by a mechanism which involves the binding of LXR/RXR to the promoters. Suppression of both the ABCA1 and ABCG1 genes may indicate that unsaturated fatty acids suppress not only cholesterol efflux to apoA-I and thereby nascent HDL formation but also HDL-dependent cholesterol efflux from vascular cells.

Evaluation of brain perfusion SPECT using an easy Z-score imaging system (eZIS) as an adjunct to early-diagnosis of neurodegenerative diseases.

UNLABELLED: The eZIS allows computer-assisted statistical analysis of brain perfusion SPECT images. We evaluated the diagnostic value of brain perfusion SPECT using eZIS in patients with various neurodegenerative diseases at a very early stage, within one year from onset. METHODS: SPECT using eZIS was performed for patients with Alzheimer disease (AD), dementia with Lewy bodies (DLB), frontotemporal dementia (FTD,), idiopathic Parkinson disease (PD) and vascular Parkinsonism (VP), multiple systemic atrophy of the cerebellar type (MSA-C), cortical cerebellar atrophy (CCA) and amyotrophic lateral sclerosis (ALS). RESULTS: Decreased rCBF was observed in the posterior cingulate cortex, precuneus and parietal cortex in AD; in the frontal gyrus and insula in FTD; in the occipital lobe, precuneus gyrus and posterior cingulate cortex in DLB; in the striatum and the thalamus in VP; in the cerebellum in CCA; in the cerebellum and pons in MSA-C and in the frontal cortex including the central sulcus in ALS. Increased rCBF in the striatum, thalamus and cerebellar dentate nuclei were observed in PD. CONCLUSIONS: A specific rCBF pattern was observed for each disease using eZIS analysis, consistent with previous reports. Our results showed eZIS can be easily used as an adjunct to early-diagnosis of neurodegenerative diseases in any hospital.

Acute motor sensory axonal neuropathy associated with Henoch-Schönlein purpura.

A 41-year-old man was admitted with progressive tetraparesis with hypoesthesia. He also presented with purpura in both legs. After admission, joint pain, gastrointestinal tract bleeding, and renal dysfunction developed. A nerve conduction study revealed reduced amplitude of the motor and sensory nerve action potential, with normal conduction velocity. A skin biopsy showed leukocytoclastic vasculitis, indicating Henoch-Schönlein purpura (HSP). After administration of corticosteroids, the symptom completely disappeared. The present case is the first report in Japan of HSP associated clinically and electrophysiologically with confirmed acute motor sensory axonal neuropathy. Common pathogenesis might have a role for development for two distinct disorders.

Aprataxin (APTX) gene mutations resembling multiple system atrophy.

Mutations of the aprataxin (APTX) gene cause early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH), also called ataxia with oculomotor apraxia type 1. Recent studies showed clinical heterogeneity in patients with EAOH. We describe 2 patients whose clinical features resembled those of multiple system atrophy of the cerebellar subtype (MSA-C) but without ocular motor apraxia and hypoalbuminemia. Each had a different nucleotide transition in the APTX gene (725G-->A and 457A-->G). These variants on the APTX gene exhibit phenotypic variability.