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

OBJECTIVE: Reports suggest that catechol-O-methyltransferase (COMT(L/L)) (Val(158)/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. chi(2), 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 COMT(L) 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 COMT(L) 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.

Hemichorea-hemiballism: an explanation for MR signal changes.

PURPOSE: Some cases of hemichorea-hemiballism (HCHB) are associated with a hyperintense putamen on T1-weighted MR images, the cause of which remains unclear. Our purpose was to determine the cause and significance of these MR signal changes. METHODS: We analyzed the clinical and neuroimaging findings in 10 patients with HCHB, focusing on locations of the hyperintense lesions on T1-weighted images, comparing them with those on CT scans, and evaluating their changes after years of follow-up. A biopsy was performed in one patient. RESULTS: Seven patients had hyperglycemia and two had cortical infarcts. HCHB recurred in four patients. A hyperintense putamen preceded the occurrence of HCHB in two patients. T1-weighted MR images revealed hyperintense lesions limited to the ventral striatum in six patients. Hyperintense lesions extended to the level of the midbrain in one patient and persisted for as long as 6 years in another patient. T2-weighted MR images revealed slit-shaped cystic lesions in the lateral part of the putamina 2 to 6 years after the onset of symptoms in two patients. A biopsy specimen from the hyperintense putamen in one patient revealed a fragment of gliotic brain tissue with abundant gemistocytes. Proton MR spectroscopy of the specimen showed an increase in lactic acid, acetate, and lipids, and a decrease in N-acetylaspartate and creatine, suggesting the presence of pronounced energy depletion and neuronal dysfunction. CONCLUSION: Gemistocytes are sufficient to explain the shortening of T1 relaxation time. Our investigation suggests that neurons in the ventral striatum and striatonigral pathway may play a critical role in generating ballism.

Gait analysis in advanced Parkinson's disease--effect of levodopa and tolcapone.

OBJECTIVE: To determine the therapeutic effect of levodopa/benserazide and tolcapone on gait in patients with advanced Parkinson's disease. METHODS: Instrumental gait analysis was performed in 38 out of 40 patients with wearing-off phenomenon during a randomized, double-blind, placebo-controlled trial of tolcapone. RESULTS: Gait analysis disclosed a significant improvement by levodopa/benserazide in walking speed, stride length and the range of motion of hip, knee and ankle joints. At the end of the study, both the UPDRS motor scores during off-period and the percentage of off time improved significantly using tolcapone. However, gait analysis could not confirm this improvement. With respect to levodopa/benserazide effect, the reduction in rigidity correlated with improved angular excursion of the ankle, whereas the decreased bradykinesia correlated with improved stride length and angular excursion of the hip and knee joints. CONCLUSION: The results of our gait analysis confirmed that in parkinsonian patients with fluctuating motor symptoms levodopa/benserazide, but not tolcapone, produced a substantial improvement.

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.

Genetic screening for Huntington's disease in Chinese patients with involuntary movements.

The diagnosis of Huntington's disease (HD) can be confirmed by detecting the expanded CAG repeat in the IT15 gene. Besides chorea, patients with HD may present with a variety of bizarre involuntary movements, resulting in confusion in making the diagnosis. Under such conditions, genetic analysis is the final confirmatory test. To determine if any patient with involuntary movements of undetermined etiology might be related to HD, we did genetic analysis on 22 patients and identified three with expanded CAG repeat. We could not obtain family history of HD in these patients due to adoption, early death of parents, or a vague history. All three patients were among the group with generalized chorea, but one had additional marked dystonic posturing. Together with four clinically recognizable HD patients, the relative frequency of HD among the 103 patients with choreiform movements in this hospital is 6.8%.

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 Parkinson's 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%) Parkinson's patients, are highly correlated with cognitive impairment. The pattern of SPECT abnormality in most demented patients with Parkinson's disease is similar to that seen in Alzheimer's disease, suggesting that the underlying pathophysiology for dementia in patients with Parkinson's disease may be similar to that in Alzheimer's disease.

Experience of pergolide in the treatment of Chinese parkinsonian patients with dose-related fluctuations.

BACKGROUND: To improve dose-related fluctuations in patients with Parkinson's disease, the efficacy of pergolide, a long-acting dopamine receptor agonist, was determined. METHODS: Using a stringent diagnostic criterion for Parkinson's disease, 20 patients were selected for a short-term open-label trial, and were divided into three groups based on the accuracy of clinical diagnosis. RESULTS: Nineteen patients completed the study. The mean dosage of pergolide was 2.89 mg per day. The total motor score improved by 34.1% during the "on" period and by 34.8% during the "off" period (p < 0.001). The recorded daily off time decreased from 40.3% to 11.5% (p < 0.001). There was no statistically significant difference in the magnitude of response among different groups of patients; however, patients with shorter duration of illness also received significantly lower dosage of pergolide. Hallucination, worsening of peak-dose dyskinesia, and lowering of blood pressure were major adverse effects. Pergolide could not prevent the occurrence of neuroleptic malignant syndrome in one patient. CONCLUSIONS: Pergolide is very effective for moderate to advanced Parkinson's disease.

An add-on study of selegiline to Madopar in the treatment of parkinsonian patients with dose-related fluctuations: comparison between Jumexal and Parkryl.

BACKGROUND: To improve dose-related fluctuations in patients with Parkinson's disease, the efficacy of selegiline, a selective inhibitor of monoamine oxidase B, was determined. METHODS: Twenty parkinsonian patients were selected for a short-term, single-blind, cross-over trial. Each patient received one of the two brands of selegiline, Parkryl (Mei-Shih), 10 mg per day as an adjunct to Madopar. After a 6-week treatment period and a 4-week wash-out period, the treatment was switched to the other brand of selegiline, Jumexal (Labatec), for another 6 weeks. RESULTS: Five patients dropped out of the study because of the development of intolerable dyskinesia, hallucination or agitation. The 15 patients that completed the study made a mild improvement in the total motor scores of the on-period during both treatments of Parkryl (p < 0.01) and of Jumexal (p < 0.05). The recorded daily off-time decreased from 37.8% to 20.7% in the Parkryl group (p < 0.01), and to 21.0% in the Jumexal group (p < 0.01). CONCLUSION: Selegiline, as an adjunct therapy to Madopar, has a moderate effect in prolonging the duration of on-time in parkinsonian patients with dose-related fluctuations. Jumexal seemed to produce no greater effect than Parkryl.

Detection of oligoclonal bands in patients with neurologic diseases: comparison between agarose gel-, immunofixation- and isoelectric-focusing electrophoresis.

BACKGROUND: The presence of oligoclonal bands (OCBs) in cerebrospinal fluid (CSF) often implies the involvement of the humoral immune response in the disease process. We compared three methods of electrophoresis to determine the frequency and pattern of OCBs in Chinese patients with various neurologic diseases. METHODS: CSF samples and matched serum samples were collected from 122 patients. OCBs were examined in all the CSF samples after agarose gel electrophoresis (AGE) or isoelectric-focusing electrophoresis (IEF); some samples were selected and concentrated for immunofixation electrophoresis (IFE). RESULTS: While 46.7% of the CSF samples showed elevated immunoglobulins using AGE, OCBs were unequivocally identified in 16.4% of samples. In contrast, the detection rate of OCBs using IEF was 54.1%, while that of monoclonal bands was 4.9%. Some OCBs could be detected by IFE, which demonstrated that most of them were IgG-kappa. Using IEF, the sensitivity was 66.7% in multiple sclerosis, 47.8% in myelopathy, 88.9% in chronic inflammatory demyelinating polyradiculoneuropathy, 62.5% in acute inflammatory demyelinating polyradiculoneuropathy, 80.0% in meningoencephalitis and 23.0% in other neurologic diseases. CONCLUSIONS: IEF was the most sensitive method for detecting OCBs. Most patients with type 2 or type 3 patterns of OCBs had multiple sclerosis or meningoencephalitis, although some of these patients may present with a type 4 pattern. Most patients with other diseases had identical patterns of OCBs in both serum and CSF.

Clinical manifestations of tardive truncal dystonia--abdominal movements: report of two cases.

A variety of involuntary abdominal movements may result from peripheral insults or have a central origin. However, the spectrum of differential diagnoses can be broadened by this report of two patients whose involuntary abdominal movements were related to chronic use of haloperidol or sulpiride. Electromyographic studies revealed two patterns of muscle activity in these two patients. The first patient showed long-duration bursts of the thoracic and lumbar paraspinal muscles, causing repetitive backward tilting of the pelvis and downward shifting of the umbilicus. The second patient showed persistent contraction of the rectus and the external oblique abdominal muscles, causing sustained retraction of the abdominal wall and episodic jerking. Both patients improved dramatically after treatment with reserpine. We conclude that electromyographic study is useful in identifying truncal dystonia and abdominal dystonia, two variants of tardive syndrome.

Absence of 4,977-bp deletion of blood cell mitochondrial DNA in patients with young-onset Parkinson's disease.

Decreased mitochondrial Complex I activities and a 4,977-bp deletion in mitochondrial DNA (mtDNA) have been reported in patients with Parkinson's disease. Based on the assumption of possible links between this 4,977-bp deletion and the etiology of Parkinson's disease, we analyzed mtDNA of blood cells from 15 patients with young-onset Parkinson's disease after the DNA was amplified by polymerase chain reaction. We could not detect the 4,977-bp mtDNA deletion in any of these patients. This result suggests that Parkinson's disease is not a mitochondrial disease due to the 4,977-bp mtDNA deletion. The 4,977-bp deletion in mtDNA appears to be an age-related phenomenon.

Reverse-phase high-performance liquid chromatography of nerve growth factor receptor-like proteins identified with monoclonal antibodies.

Human neuroblastoma SK-N-SH-SY5Y (SY5Y) and rat pheochromocytoma PC12 cells are model cell lines used in the study of nerve growth factor (NGF) effect. The effects of NGF are initiated by binding to cell surface receptors (NGFR). The amino acid sequence for NGFR has been deduced based on the identification of a single gene for NGFR. However, there are two kinds of NGF binding activities and several reported molecular weights of NGFR. We report here on the demonstration of NGFR-like proteins from PC12 and SY5Y cells by sequential lectin chromatography, reverse-phase HPLC, and SDS-PAGE analysis of immunoprecipitates obtained with NGFR-specific monoclonal antibodies. For both human and rodent NGFR, there was a tendency for the higher molecular-weight species of NGFR-like proteins to be eluted in more hydrophobic fractions. Also, the expression of different species of NGFR could be modified by treatment with retinoic acid (RA). These results are consistent with the hypothesis that the different molecular species of NGFR may result from the generation of a truncated form of NGFR, the presence of sugar residues on the NGFR protein, dimer formation between NGFR, or the association of NGFR with a receptor-associated protein.

Non-obstructive idiopathic pachymeningitis cervicalis hypertrophica.

Two young men had similar nonobstructive idiopathic pachymeningitis cervicalis hypertrophica, causing chronic (13 and 11 years respectively) C8-T1 radiculomyelopathy proved by surgical and pathological findings. The preoperative Queckenstedt tests and myelography showed no evidence of CSF obstruction. These unusual findings contrast with previous reports which all described complete or at least partial, block. The findings on metrizamide computed tomogram have not been described before. In the two patients it revealed diffuse cord atrophy from C7 to T2 and hemiatrophy with lateral beaking from C4 to C7. The patients benefited from multiple transverse durotomies. The main pathogenesis of the cord atrophy was the compromizing of feeding radicular arteries rather than direct compression.

A SPECT study of patients with gait apraxia without evidence of frontal lobe dysfunction.

BACKGROUND: The pathogenesis of gait apraxia (GA) is unknown. Even though imaging studies provide excellent assessment of brain morphology, there is still a lack of congruous results. Single photon emission computed tomography (SPECT) using Tc-99m hexamethylpropyleneamine oxime (HMPAO) may show alterations in regional cerebral blood flow (rCBF) and provide indirect information about brain metabolism. METHODS: We conducted a SPECT study of GA patients and evaluated the related cortical function. rCBF was assessed in 16 GA patients (15 male, one female; age range 65-79 years, mean 70.5 years) by SPECT using HMPAO. Mean HMPAO cortical or basal ganglia/cerebellum activity ratios were calculated. The regions of interest included the frontal lobe, parietal lobe and basal ganglia. A battery of GA tests and magnetic resonance imaging (MRI) of the brain were also performed in these 16 patients. RESULTS: Nine of the patients had equilibrium disorder, and all 16 patients had locomotion disorder. The MRI findings were lacunar infarct (16/16 in basal ganglia, or 6/16 in thalamus), leukoaraiosis (4/16), enlarged ventricle (3/16), frontal lesion (3/16) and parietal lesion (1/16). Lower rCBF was noted in the frontal lobe (3/16), occipital lobe (1/16, thalamus (7/16) and basal ganglia (9/16). Though SPECT showed decreased rCBF in nine patients (9/16), mean cortical and basal ganglia regional uptake ratios in the patient group were not significantly different from values in the control group (cortical p = 0.0613; basal ganglia p = 0.0576, by Student's t-test). CONCLUSIONS: Though only a small number of patients were studied, it was clear that brain SPECT and MRI did not show any significant abnormalities in the frontal or parietal lobes of patients with GA. Thus, the pathogenesis of GA and its related anatomic lesion should be further investigated.

Polyneuropathy associated with acute monoblastic leukemia: a case report.

Polyneuropathy associated with acute myelocytic leukemia is rare. We report a woman aged 34 years with acute monoblastic leukemia and polyneuropathy in hematology remission. The clinical, electrophysiological and pathological findings revealed acute symmetrical sensorimotor axonal polyneuropathy that differs from previous reports of three cases.

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.

Technetium-99m hexamethylpropylene amine oxime single photon emission tomography of the brain in early Parkinson's disease: correlation with dementia and lateralization.

Regional cerebral blood flow was assessed in 19 patients with early idiopathic Parkinson's disease (PD) and 12 control subjects of similar age by single-photon emission tomography using technetium-99m hexamethylpropylene amine oxime (HMPAO). Of the patients with PD, seven were mildly demented and 15 presented with hemiparkinsonism. Mean HMPAO cortical or basal ganglia/cerebellum activity ratios were calculated. Mean cortical and regional uptake ratios in non-demented PD patients were not significantly different from values in the controls. In contrast, besides generalized cortical hypoperfusion, demented PD patients had significantly lower HMPAO uptake in the frontal and basal ganglia regions than non-demented patients. These observations support the hypothesis of impaired neuronal activity in both cortical and subcortical regions of the brain in demented PD patients. In hemiparkinsonian patients, the only asymmetrical finding was a relative hypoperfusion in the contralateral parietal region. This may be due to deafferentation of the thalamoparietal pathways. The lack of asymmetrical uptake in basal ganglia in our PD patients may be explained by their staging at the time of the investigation (stage I and II, Hoehn and Yahr scale).

Sympathetic skin response and R-R interval variation in Parkinson's disease.

We investigated autonomic function in patients with idiopathic Parkinson's disease (PD) by measuring sympathetic skin response (SSR) and R-R interval variation (RRIV). Sixty-two PD patients and 62 age-matched normal subjects were recruited. Abnormal SSR was noted in nine (14.5%) PD patients, including three in Stage II, three in Stage III, and three in Stage IV, but not in Stage I patients or normal subjects. Four of these nine patients had postural hypotension. Abnormal SSR was correlated with duration of illness and impotence. In PD patients, abnormal SSR may be due to intermediolateral column dysfunction. After logarithmic transformation and age adjustment, 19 (31.6%) of 60 PD patients had abnormal RRIV during rest and deep breathing. Abnormal RRIV was not related to staging or duration of illness. Patients with constipation had significantly lower RRIV, indicating parasympathetic dysfunction. RRIV was not affected by acute or chronic L-dopa treatment. The agreement between RRIV and SSR in PD patients was poor (kappa = -0.07). It appears that abnormal SSR, but not RRIV, may be associated with more autonomic disturbances in PD patients.

Single-pulse transcranial magnetic stimulation reset the rhythm of essential tremor but not heart beat.

BACKGROUND: Human oscillator is observed in and outside the nervous system. Cardiac rhythm is generated by heart itself but can be modulated by brain. Using the technique of transcranial magnetic stimulation (TMS) and resetting index, we studied if single-pulse TMS could reset the cardiac rhythm and help differentiate oscillator of neurogenic or non-neurogenic origin. METHODS: In addition to the study of 4 patients with essential tremor, cardiac rhythm was studied in 6 normal subjects. The magnetic intensity was initiated from motor threshold of hand muscle, and then with an increment of 10% up to the maximal output of magnetic stimulator. We used the resetting index (RI) to quantify the influence of the TMS. RESULTS: The resetting phenomenon was observed in essential tremor (RI = 0.92) but not in cardiac rhythm (RI = 0.02). CONCLUSIONS: Single-pulse TMS is able to reset the rhythm of essential tremor but not heart beat. The pacing mechanism is different between essential tremor and heart beat. The cardiac rhythm is regulated and modulated chiefly by heart itself. Essential tremor should not share the same mechanism with heart beat.

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

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 Parkinson's 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.