Combined (thalamotomy and stimulation) stereotactic surgery of the VIM thalamic nucleus for bilateral Parkinson disease

Stereotactic thalamotomy of the thalamic nucleus ventralis intermedius (VIM) is routinely used for movement disorders. During this procedure, it has been observed that high-frequency (100 Hz) stimulation of VIM was able to stop the extrapyramidal tremor. In patients with bilateral tremor of extrapyramidal origin, who were resistant to drug therapy, the therapeutic protocol associated (1) a radiofrequency VIM thalamotomy for the most disabled side, and (2) a continuous VIM stimulation for the other side using stereotactically implanted electrodes, connected to subcutaneous stimulators. VIM thalamotomy relieved the tremor in all operated cases. Side effects were mild and regressive. VIM stimulation strongly decreased the tremor but failed to suppress it as completely as thalamotomy did. This was due in part to the fact that programmable stimulator frequency rate is limited to 130 Hz, while it appeared that the optimal stimulation frequency was 200 Hz. This therapeutic protocol appears to be of interest for patients with bilateral extrapyramidal movement disorders.     

Present role of stereotactic thalamotomy for parkinsonism. Retrospective analysis of operative results and thalamic lesions in computed tomograms

14 cases of unilateral and 5 cases of bilateral thalamotomy for parkinsonism were reviewed, with 32-144 months' (mean 67.8) and 54-212 months' (mean 110) follow-up, respectively, after the initial operation. Rigidity and tremor disappeared in approximately 80% of cases and was reduced in the remaining 20%. 68% improved by one or two grades in the Hoehn-Yahr scale after operation. Thalamotomy abolished dyskinesias and on-off phenomena on the operated sides. 36% of cases discontinued levodopa therapy after operation. CT study of the lesions suggested that destruction of a large part of basal Vop was most important to obtain the best results.     

Long-term follow-up study of nucleus ventralis intermedius and ventrolateralis thalamotomy using a microelectrode technique in parkinsonism

Long-term observation over 3-8 postoperative years of cases of Parkinson disease operated by stereotactic thalamotomy using a microelectrode recording technique is reported. The procedure is specifically useful in the following four groups: (1) tremor-dominant cases, (2) hemiparkinsonism, (3) cases with marked asymmetry in motor symptoms and (4) juvenile parkinsonism presenting levodopa-induced dyskinesia.     

Target identification for stereotactic thalamotomy using diffusion tractography

Background

Stereotactic targets for thalamotomy are usually derived from population-based coordinates. Individual anatomy is used only to scale the coordinates based on the location of some internal guide points. While on conventional MR imaging the thalamic nuclei are indistinguishable, recently it has become possible to identify individual thalamic nuclei using different connectivity profiles, as defined by MR diffusion tractography.

Methodology and Principal Findings

Here we investigated the inter-individual variation of the location of target nuclei for thalamotomy: the putative ventralis oralis posterior (Vop) and the ventral intermedius (Vim) nucleus as defined by probabilistic tractography. We showed that the mean inter-individual distance of the peak Vop location is 7.33 mm and 7.42 mm for Vim. The mean overlap between individual Vop nuclei was 40.2% and it was 31.8% for Vim nuclei. As a proof of concept, we also present a patient who underwent Vop thalamotomy for untreatable tremor caused by traumatic brain injury and another patient who underwent Vim thalamotomy for essential tremor. The probabilistic tractography indicated that the successful tremor control was achieved with lesions in the Vop and Vim respectively.

Conclusions

Our data call attention to the need for a better appreciation of the individual anatomy when planning stereotactic functional neurosurgery.     

Long-term follow-up results of bilateral thalamotomy for parkinsonism.

27 patients who underwent bilateral thalamotomy for parkinsonism over the past 10 years have been clinically evaluated. Mean follow-up period was 6.2 years after second surgery. In these cases, 8 returned to full social life without any medication, 4 were capable of social life with medical treatment, 6 were self-sufficient and 3 were semi-self-sufficient in ADL, respectively. Therapeutic drug doses were reduced in all cases. L-Dopa-induced dyskinesia was not observed after second surgery. Speech disturbance, which was not severe, was recognized in 12 cases as a complication.     

Changes in cerebral blood flow after stereotactic thalamotomy

Regional cerebral blood flow (rCBF), a parameter of neuronal activity in the brain, was measured by the 133Xe inhalation method in 43 patients undergoing stereotactic thalamotomy. A postoperative flow reduction of about 2% in the operated hemisphere was found, persisting in further measurements performed after a year. There was no consistent change in the pattern of regional flow distribution. The results indicate a diminished level of activity in the hemisphere subjected to thalamotomy, but the change could not be linked to any specific area or function.     

Estimation of neural noise. Functional anatomy of the human thalamus.

In the course of stereotactic thalamotomy, the neural noise level of subcortical structures was estimated quantitatively with the aid of two semimicro-electrodes. The neural noise showed several characteristic features in terms of its amplitude and discharge pattern so that it was correlated with the possible anatomical substrate, thus providing the functional anatomy of the subcortical structures. The study on saggital plane revealed a systematic difference of the noise level between VL and Vim-Vc that could be explained by the different cell size in respective nucleus. Several exceptional cases were also presented, emphasizing the neural noise study in stereotactic surgery.     

Second polar body inclusion results in diploid/triploid mixoploidy

We report three cases with a typical diploid/triploid mixoploidy. Cytogenetic analysis showed a normal diploid karyotype in peripheral blood lymphocytes and a mixture of diploid and triploid cells in skin fibroblasts. We analysed microsatellite markers in patients blood lymphocytes and skin fibroblasts and compared the results with the microsatellite markers in the parents. The extra haploid set was in all three cases of maternal origin. In one case the markers were not very informative but in two cases pericentromeric markers showed a single dose of one paternal allele and a double dose of one maternal allele, more telomeric markers showed one paternal allele and two different maternal alleles. These observations can only be explained by the inclusion of the second polar body in one of the blastomeres at the cleavage stage.     

A clinical,pneumoencephalographic and radioisotopic study of normal-pressure communicating hydrocephalus

Human serum albumin labelled with iodine-133 or technetium-99^m was injected by the lumbar or cisternal route into patients suspected of having communicating hydrocephalus, and scintigrams were performed up to 24 hours after injection.The CSF isotope studies were shown to be a valuable adjunct to clinical examination and pneumoencephalography in the diagnosis of hydrocephalus. This was especially true in suspected cases of “normal”-pressure hydrocephalus where there may be considerable uncertainty as to which patients with normal pressure and enlarged ventricles will benefit from a shunting procedure. The CSF isotope study provides useful information to the clinician in differentiating patients with symptomatic hydrocephalus from the larger group with dementia, cerebral atrophy and hydrocephalus ex vacuo.     

Hypokalaemia after Pneumoencephalography

The changes in plasma electrolytes and blood pH and gases following the insufflation of air into the subarachnoid space for pneumoencephalography were investigated. The only significant change observed was a rapid fall of plasma potassium most evident at 60 minutes. A concomitant reduction of the urinary Na/K ratio supports the possibility that the change observed may be due to the stimulation of aldosterone secretion caused by this procedure, though its rapid occurrence and reversibility indicate that other influences might at least in part be responsible.     

Management of Parkinson's Disease: Combined Therapy with Levodopa and Thalamotomy

An increasing number of parkinsonian patients in whom levodopa fails to relieve tremor are being referred for thalamotomy. The literature suggests that in as many as 50 percent of patients treated with levodopa, there is no relief of tremor because of refractoriness to the medication or intractable side effects which limit dosage. Thalamotomy abolishes contralateral tremor in 90 percent of patients, with an associated mortality rate of 1 to 2 percent and morbidity of 6 percent. The relative merits and complications of levodopa and thalamotomy were reviewed and a therapeutic regimen designed in which the two approaches to treatment are combined to most effectively deal with all the symptoms of parkinsonism.     

Combined stereotactic and peripheral surgical approach for spasmodic torticollis.

Thalamotomy with or without pallidotomy and peripheral denervation, if necessary, was performed in 14 cases of spasmodic torticollis or other late dystonias. Of 4 bilateral procedures, 2 had a good result, in 1 there was little change and in another the patient remained with a pseudobulbar syndrome, the only complication in this group. 1 patient only required peripheral denervation with a good result. Of the 9 patients who underwent unilateral thalamotomy, with or without pallidotomy, the result was excellent in 6 and good in 2 others, but in 4 of these 8 patients peripheral denervation was also performed.     

Effect of phagocytosis on guinea pig granulocyte membrane markers

The internalization of membrane markers during phagocytosis was followed in guinea pig granulocytes as a function of the extent of particle ingestion. The plasmalemma was carefully labeled with diazotized ³⁵S-sulfanilate, or by treatment with periodate and sodium ³H-borohydride. These treatments provided general membrane markers. More specific markers used were 5′-nucleotidase, neuraminidase-releasable membrane sialate, and concanavalin A binding sites. In all cases except the last, internalization of membrane was directly determined on isolated phagosomes; disappearance of binding sites from the cell surface was followed in the last instance. Both phagosomal levels and disappearance from the surface were measured in the case of 5′-nucleotidase, permitting balance studies. Phagocytosis was determined as uptake of paraffin emulsions labeled with Oil-Red 0. “Marker/particle” ratios were determined as the percent external marker internalized per mg paraffin ingested. The “marker/particle” ratios for cells with chemically labeled membranes were considered to reflect random internalization of membrane entities. Colchicine had no effect on those ratios. Internalization of 5′-nucleotidase and neuraminidase-releasable sialate gave “marker/particle” ratios similar to those of the random markers, and these increased in the presence of colchicine. Concanavalin A binding sites did not appear to be removed from the cell surface in the absence of colchicine, but disappearance was observed in its presence. Control experiments indicated that these changes due to colchicine must be very cautiously interpreted. Our results differ from those obtained by others, and the reasons due to species, cell type, experimental design, etc. are discussed. Maximal particle uptake was computed to require internalization of one-fifth to one-third of the total external membrane of the cells—based on the assumption of random internalization of markers.     

Possible utility of serum determinations of CA 125 and CA 27.29 in breast cancer management

The utility of measurement of serum levels of the tumor associated antigens CA 125 and CA 27.29 in detecting the presence of disease and in monitoring changes in disease status was examined in 63 patients with breast cancer. In patients with clinically detectable disease the CA 125 level was elevated in 59%, the CA 27.29 level in 59.5% and one or both markers in 84.6%. Specificity for presence of disease was 83.6% for CA 125, 88% for CA 27.29, and 69.1% for the two markers combined. Changes in marker levels of more than 50% correlated with clinical changes in disease status in 58% of cases for either CA 125 or CA 27.29 alone. In 87.5% of cases with clinically progressive disease one or both marker levels increased by more than 50% from the previous levels. In no case with greater than 50% increase in a marker level was there regression of disease. Thus, the use of these markers in combination might have utility in cases where diagnosis of recurrent disease is difficult or where monitoring of response to treatment is hampered by lack of measurable disease.     

What happened to VIM thalamotomy for Parkinson's disease?

A prospective review of 75 of 190 parkinsonian patients undergoing unilateral thalamotomy was displayed with a computer graphics technique examining three equal consecutive groups from the pre-, early, and late L-dopa eras. Histograms for average function and scattergrams of individual patient's performance preoperatively and up to 2 years postoperatively were prepared. No ipsilateral effects or consistent iatrogenic deterioration of any function were identified. 2 years after surgery, 82% had no tremor in the contralateral fingers or hand and 7% had almost no tremor; contralateral tremor elsewhere was infrequent. Rigidity and manual dexterity improved less strikingly, the latter only reflecting abolition of tremor; locomotion, speech, facial movement and handwriting did not improve. There was no mortality, but 8% had persistent significant complications. VIM thalamotomy remains the treatment of choice for severe drug-resistant parkinsonian tremor.     

Dominant hereditary inclusion-body myopathy gene (IBM3) maps to chromosome region 17p13.1

We recently described an autosomal dominant inclusion-body myopathy characterized by congenital joint contractures, external ophthalmoplegia, and predominantly proximal muscle weakness. A whole-genome scan, performed with 161 polymorphic markers and with DNA from 40 members of one family, indicated strong linkage for markers on chromosome 17p. After analyses with additional markers in the region and with DNA from eight additional family members, a maximum LOD score (Zmax) was detected for marker D17S1303 (Zmax=7.38; recombination fraction (theta)=0). Haplotype analyses showed that the locus (Genome Database locus name: IBM3) is flanked distally by marker D17S945 and proximally by marker D17S969. The positions of cytogenetically localized flanking markers suggest that the location of the IBM3 gene is in chromosome region 17p13.1. Radiation hybrid mapping showed that IBM3 is located in a 2-Mb chromosomal region and that the myosin heavy-chain (MHC) gene cluster, consisting of at least six genes, co-localizes to the same region. This localization raises the possibility that one of the MHC genes clustered in this region may be involved in this disorder.     

无环鸟苷抗乙型肝炎病毒复制长短程疗法随访观察

慢性乙型肝炎病毒感染s5例,随机分无环鸟苷长程组22例,短程组11例和对照组22例。经一年随访观察,无环鸟苷治疗组见血清HBeAg、DNA-P和HBV-DNA有规律性阴转,短程组于12个月又有部分指标阳转,长程组阴转较多,其血清HBeAg、DNA-P和HBV-DNA阴转率与短程和对照组比较有显著性差异。一年结果四项病毒复制指标全部阴转例数与对照组有显著性差异,结果表明,无环鸟苷长疗程是有较好疗效。     

Detection and parameter estimation for quantitative trait loci using regression models and multiple markers

A strategy of multi-step minimal conditional regression analysis has been developed to determine the existence of statistical testing and parameter estimation for a quantitative trait locus (QTL) that are unaffected by linked QTLs. The estimation of marker-QTL recombination frequency needs to consider only three cases: 1) the chromosome has only one QTL, 2) one side of the target QTL has one or more QTLs, and 3) either side of the target QTL has one or more QTLs. Analytical formula was derived to estimate marker-QTL recombination frequency for each of the three cases. The formula involves two flanking markers for case 1), two flanking markers plus a conditional marker for case 2), and two flanking markers plus two conditional markers for case 3). Each QTL variance and effect, and the total QTL variance were also estimated using analytical formulae. Simulation data show that the formulae for estimating marker-QTL recombination frequency could be a useful statistical tool for fine QTL mapping. With 1 000 observations, a QTL could be mapped to a narrow chromosome region of 1.5 cM if no linked QTL is present, and to a 2.8 cM chromosome region if either side of the target QTL has at least one linked QTL.     

Power of exclusion of 19 microsatellite markers for parentage testing in river buffalo (Bubalus bubalis)

In the present study, 19 microsatellite markers were assessed for their power of exclusion to test parentage in river buffalo. Microsatellite genotypes of 216 unrelated buffaloes belonging to five different breeds were utilized for the study. The probabilities of exclusion were calculated for three hypothetical situations viz. paternity testing (PE1), one parental genotype unavailable (PE2) and exclusion of both parents i.e. substituted offspring (PE3). The mean probability of exclusion across 19 investigated markers in buffalo was 0.578 (PE1), 0.405 (PE2) and 0.764 (PE3) respectively. The probability of exclusion for paternity (PE1) ranged between 0.297 and 0.814 across different markers. The exclusion probability for the cases one parent unavailable (PE2) and substituted offspring (PE3) varied from 0.143 to 0.688 and 0.465 to 0.946 respectively. Polymorphism information content and expected heterozygosity were found to have significantly high correlation with probability of exclusion of microsatellite markers. The cumulative PE1 of nine marker loci was estimated to be 0.9999 while in case of absence of one of the parental genotypes, a minimum of 11 markers were required to achieve a cumulative PE2 of 0.999. In conclusion, the present study proposes two multiplex sets with four and five markers respectively for routine parentage testing in buffalo and an additional set of four markers for doubtful cases of paternity.     

Analysis of tremulous movements after thalamotomy correlated to intrathalamic therapeutic lesions.

Residual tremulous movements after thalamotomy were examined using an accelerometer and EMG. Various types of tremor-provoking procedures were performed and the tremulous movements were classified according to the pattern of modificiation by these procedures. Four types of postoperative tremulous movements were noted, and a correlation was made to the intrathalamic therapeutic lesions.