Din-E Shan

Spinocerebellar ataxia type 2 presenting as familial levodopa-responsive parkinsonism

A genetic analysis identified 2 patients, approximately one‐tenth of our patients with familial parkinsonism, who had expanded trinucleotide repeats in SCA2 genes. The reduction of 18F‐dopa distribution in both the putamen and caudate nuclei confirmed that the nigrostriatal dopaminergic system was involved in parkinsonian patients with SCA2 mutation.

The COMT L allele modifies the association between MAOB polymorphism and PD in Taiwanese

Objective: Reports suggest that catechol-O-methyltransferase (COMTL/L) (Val158/Met) and monoamine oxidase B (MAOB) intron 13 genotype polymorphism is associated with PD. To understand the ethnicity-specific effects of genetic polymorphism, we performed a case-control study of the association between PD susceptibility and polymorphism of MAOB and COMT, both separately and in combination, in Taiwanese. Methods: Two hundred twenty-four patients with PD and 197 controls, matched for age, sex, and birthplace, were recruited. MAOB and COMT polymorphism genotyping was performed by using PCR-based restriction fragment length polymorphism (RFLP) analyses. χ2, OR, and Fisher’s exact tests were used to compare differences in allelic frequencies and genotypes. Results: The MAOB G genotype (G in men and G/G in women) was associated with a 2.07-fold increased relative risk of PD. COMT polymorphism, considered alone, showed no correlation with PD risk; however, a significant synergistic enhancement was found in PD patients harboring both the COMTL and MAOB G genotypes. Conclusions: These results suggest that, in Taiwanese, PD risk is associated with MAOB G intron 13 polymorphism, and this association is augmented in the presence of the COMTL genotype, indicating an interaction of these two dopamine-metabolizing enzymes in the pathogenesis of sporadic PD. However, the relatively low frequencies of these combined genotypes in our study necessitates confirmation with a larger sample size.

Clinical, 18F-dopa PET, and genetic analysis of an ethnic Chinese kindred with early-onset parkinsonism and parkin gene mutations.

We report on clinical 18F‐labeled 6‐fluorodopa (18F‐dopa) positron emission tomography (PET) and molecular genetic analyses of an ethnic Chinese family in which three siblings presented with early‐onset Parkinsons disease. As described in some parkin patients, neither sleep benefit nor diurnal fluctuation was noted. Interestingly, depression, anxiety, and obsessive–compulsive disorders were manifest. The 18F‐dopa PET scans showed bilateral presynaptic dopaminergic dysfunction without marked lateralization. Molecular genetic analysis showed identical chromosome 6 haplotypes inherited by affected subjects, with alternate allelic deletions of parkin exons 3 and 4. Furthermore, mRNA analyses identified aberrantly spliced parkin transcripts, suggesting that unusual parkin protein isoforms may be expressed in the brain and retain some function.

Cognition and 99Tcm-HMPAO SPECT in Parkinson's disease

99Tcm-hexamethylpropyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT) of brain was performed in 43 unselected patients with Parkinsons disease to evaluate whether low cerebral perfusion on SPECT correlated with cognitive impairment in the patients. All patients received neurological, Mini-Mental State Examination and a neuropsychological assessment. Eighteen (41.9%) of the 43 patients were demented. Thirty patients (69.8%) had abnormal SPECT: 17 had perfusion defects in cortical regions, eight in basal ganglia and five in both regions. Of the 22 patients with abnormal cortical perfusion, 15 (68.2%) were demented; only three (14.3%) of the 21 patients without cortical defect were demented (P < 0.01). Twelve of the 15 demented patients had low perfusion in the parietal region alone or in parietal and occipital regions. The cortical perfusion defects, present in 22 (51.2%) Parkinsons patients, are highly correlated with cognitive impairment. The pattern of SPECT abnormality in most demented patients with Parkinsons disease is similar to that seen in Alzheimers disease, suggesting that the underlying pathophysiology for dementia in patients with Parkinsons disease may be similar to that in Alzheimers disease.

Presence of spinocerebellar ataxia type 2 gene mutation in a patient with apparently sporadic Parkinson's disease: clinical implications.

Among 242 patients with apparently sporadic Parkinsons disease, a 70‐year‐old man with a CAG repeat number of 37 in the SCA2 gene was identified. He has remained responsive to levodopa 14 years after onset and has had no overt signs suggesting cerebellar dysfunction. Although it is not possible to confirm if this patient has a de novo mutation of the SCA2 gene, this genetic defect seems to be contributing to his parkinsonian features and further supports the concept that apparently sporadic, late‐onset, levodopa‐responsive Parkinsons disease may have multiple causes.

Val-9Ala and Ile + 58Thr polymorphism of MnSOD in Parkinson's disease

OBJECTIVES To investigate the polymorphism distribution of Val-9Ala and Ile+58Thr of the Mn-superoxide dismutase (Mn-SOD) gene among subjects with Parkinsons disease (PD) by analyses of genders and clinical severity. DESIGN AND METHODS We examined the DNA genotypes of Val-9Ala and Ile+58Thr from 295 PD subjects and 111 controls by nucleotide sequencing and BsaWI restriction. RESULTS Ala/Ala homozygosity was found in four PD subjects but not in the controls. All of the genotypes at codon +58 among the examined samples were Ile/Ile homozygotes. Although higher carrier rate of Ala allele among PD subjects than the controls, there were no differences by analyses of the genders and clinical severity. CONCLUSION The higher Ala-allele carrier rate among PD subjects may suggest a possible higher amount of mitochondrial Mn-SOD rendering higher intracellular stress in PD. In this study the polymorphisms at codons -9 and+58 did not give informative association evidences with PD.

Guillain–Barré syndrome coexisting with pericarditis or nephrotic syndrome after influenza vaccination

A 68-year-old woman and a 72-year-old man presented with distal weakness of the limbs and numbness following an influenza vaccination within 2 weeks. Moreover, Guillain-Barré syndrome (GBS) was diagnosed in two patients. Pericarditis was diagnosed in the first patient who also had precordial chest pain with referral to trapezius ridge, and nephrotic syndrome, was observed in the second patient who had leg edema and proteinuria. The relationship among GBS, pericarditis and nephrotic syndrome after an influenza vaccination is discussed.

Genetic polymorphism of the CYP2E1 gene and susceptibility to Parkinson's disease in Taiwanese

Summary. Cytochrome P450IIE1 (CYP2E1), an ethanol-inducible cytochrome P450 enzyme, is expressed in the basal ganglia and is probably involved in the activation of neurotoxicants, producing free radical metabolites and resulting in oxidative stress. To examine the association between CYP2E1 polymorphism and the risk of Parkinsons disease (PD), we performed a case-control study on a large population of Taiwanese PD patients, focusing especially on early-onset PD patients (onset at, or before, the age of 50). Two hundred and thirty-four PD patients and 251 age- and sex-matched controls were recruited. A much higher frequency of the uncommon c2 allele was seen in our control subjects than in Caucasians (0.23 vs. 0.02). There were no significant differences between PD patients and controls in the distribution of either allelic or genotype frequencies. Our results suggest that CYP2E1 is not a major or independent determinant in the occurrence of PD in Taiwanese.

Isolated lateropulsion of the trunk in cerebellar infarct

MRI in a 63-year-old male with isolated lateropulsion of the trunk disclosed an infarct in the inferior portion of the right cerebellar hemisphere, suggesting an end-zone type infarct in the lateral branch of the right posterior inferior cerebellar artery (1PICA) or a borderzone infarct between 1PICA and superior cerebellar artery. A close clinico-topographical relationship between isolated lateropulsion of the trunk and lesion in the territory of 1PICA was demonstrated.

Hypotension Due to Interaction Between Lisinopril and Tizanidine

OBJECTIVE To report a case in which significant hypotension occurred after initiation of tizanidine in a patient using the antihypertensive agent lisinopril. CASE SUMMARY A 48-year-old woman was admitted due to cerebral hemorrhage at the midbrain and pons, with extension to the fourth ventricle. Consciousness disturbance (Glasgow coma scale 4) with a decerebrate posture improved 5 days after stroke onset. As the BP was fairly high, antihypertensive agents, including lisinopril, were initiated. Three weeks later, the decerebrate rigidity and high BP remained, and tizanidine was initiated to see whether the decrease in muscle tone could facilitate hypertension control and motor recovery. However, the BP dropped dramatically within 2 hours after the first dose of tizanidine. The tizanidine and all of the antihypertensive medications were withdrawn. Tizanidine was used again after her BP had stabilized, but did not produce similar problems. DISCUSSION A similar event was reported in 2000. The reaction in our patient appeared after tizanidine initiation and improved after both lisinopril and tizanidine were discontinued. According to the Naranjo probability scale, this was classified as a possible drug interaction. This kind of reaction is seldom mentioned as occurring during co-administration with tizanidine. With its characteristics, tizanidine has the potential to compromise hemodynamic stability during concomitant angiotensin-converting enzyme inhibitor use. CONCLUSIONS Based upon the literature review, the hypotension in this patient was possibly due to the interaction between tizanidine and lisinopril.