Secondary paroxysmal dyskinesias.

Paroxysmal dyskinesias (PxDs) are involuntary, episodic movements that include paroxysmal kinesigenic (PKD), paroxysmal nonkinesigenic (PNKD), and paroxysmal hypnogenic (PHD) varieties. Although most PxDs are primary (idiopathic or genetic), we found 17 of our 76 patients with PxD (22%) to have an identifiable cause for their PxD (10 men; mean age, 41.4 years). Causes included peripheral trauma (in three patients), vascular lesions (in four), central trauma (in four), kernicterus (in two), multiple sclerosis (in one), cytomegalovirus encephalitis (in one), meningovascular syphilis (in one), and migraine (in one). The latency from insult to symptom onset ranged from days (trauma) to 18 years (kernicterus), with a mean of 3 years. Nine patients had PNKD, two had PKD, five had mixed PKD/PNKD, and one had PHD. Hemidystonia was the most common expression of the paroxysmal movement disorder, present in 11 patients. Both of the patients with PKD had symptom durations of <5 minutes. Symptom duration ranged from 10 seconds to 15 days for PNKD and from 5 minutes to 45 minutes for mixed PKD/PNKD. There were no uniformly effective therapies, but anticonvulsant drugs, clonazepam, and botulinum toxin injections were the most beneficial. Awareness of the variable phenomenology and the spectrum of causes associated with secondary PxD will allow for more timely diagnosis and early intervention.     

Thrombin activatable fibrinolysis inhibitor and hemostatic changes in patients with type I diabetes mellitus with and without microvascular complications.

We investigated thrombin activatable fibrinolysis inhibitor (TAFI) and its influence on fibrinolysis by measuring pro-TAFI activity and total TAFI antigen in 38 patients with type I diabetes mellitus (18 with and 20 without microvascular complications), as well as in 20 healthy controls. The pro-TAFI levels in the two groups of patients did not differ from those in the control group. Total TAFI antigen [i.e. pro-TAFI, TAFI and inactive carboxypeptidase U (TAFIi)] tended to decrease in both the patient groups (59.7 +/- 7.2 and 73.4 +/- 8.9% with and without microvascular complications, respectively) compared with controls (91.9 +/- 12.2%) (P = 0.12). We also assessed the overall hemostatic potential (OHP) in plasma, the clot lysis time and the overall fibrinolytic potential. The OHP was significantly higher in patients with complications compared with controls (8.9 +/- 0.9 versus 6.7 +/- 0.4; P < 0.05) and also higher in the diabetics without complications (7.8 +/- 0.6), although the latter difference did not reach statistical significance. Levels of clot lysis time and overall fibrinolytic potential were similar in the two groups of patients and the controls. The increased OHP in plasma from diabetic patients with microvascular complications indicates an imbalance of the hemostatic system towards a prothrombotic state. No signs of impaired fibrinolysis were observed in patients with diabetes. Using the OHP method for estimation of overall hemostasis, it seems that TAFI does not influence either fibrinolysis or the increased thrombotic potential observed in patients with type I diabetes mellitus.     

Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Process, format, and clinimetric testing plan.

This article presents the revision process, major innovations, and clinimetric testing program for the Movement Disorder Society (MDS)-sponsored revision of the Unified Parkinson's Disease Rating Scale (UPDRS), known as the MDS-UPDRS. The UPDRS is the most widely used scale for the clinical study of Parkinson's disease (PD). The MDS previously organized a critique of the UPDRS, which cited many strengths, but recommended revision of the scale to accommodate new advances and to resolve problematic areas. An MDS-UPDRS committee prepared the revision using the recommendations of the published critique of the scale. Subcommittees developed new material that was reviewed by the entire committee. A 1-day face-to-face committee meeting was organized to resolve areas of debate and to arrive at a working draft ready for clinimetric testing. The MDS-UPDRS retains the UPDRS structure of four parts with a total summed score, but the parts have been modified to provide a section that integrates nonmotor elements of PD: I, Nonmotor Experiences of Daily Living; II, Motor Experiences of Daily Living; III, Motor Examination; and IV, Motor Complications. All items have five response options with uniform anchors of 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. Several questions in Part I and all of Part II are written as a patient/caregiver questionnaire, so that the total rater time should remain approximately 30 minutes. Detailed instructions for testing and data acquisition accompany the MDS-UPDRS in order to increase uniform usage. Multiple language editions are planned. A three-part clinimetric program will provide testing of reliability, validity, and responsiveness to interventions. Although the MDS-UPDRS will not be published until it has successfully passed clinimetric testing, explanation of the process, key changes, and clinimetric programs allow clinicians and researchers to understand and participate in the revision process.     

Autopsy-proven Huntington's disease with 29 trinucleotide repeats.

Huntington's disease (HD) is a neurodegenerative disorder associated with expansion of CAG trinucleotide repeats in the huntingtin gene. A minimum of 36 CAG repeats is usually reported in patients with clinical features of HD; 30 to 35 repeats represent an intermediate range. Here we report a 65-year-old male with autopsy-proven HD and 29 CAG repeats.     

Soleus H-reflex measures in patients with focal and generalized dystonia.

OBJECTIVE: The purpose of this study was to examine neurophysiological characteristics of dystonia patients using electromyographic soleus H-reflex methods. METHODS: Thirty normal healthy individuals were compared to 27 patients with focal (cervical) or generalized dystonia. Three H-reflex assessment methods were included: the ratio of maximum H-reflex to direct muscle potential (H/M ratio); vibration inhibition (H(v)/H(c) ratio); and H-reflex recovery curves (HRRC). RESULTS: Average H/M ratios between groups were not statistically significant. The average H(v)/H(c) ratio for the generalized dystonia group was significantly greater than the focal dystonia and normal groups. Average values of the HRRC showed the generalized dystonia group had significantly greater disinhibition than the focal dystonia and control groups during the early inhibition phase. The HRRC for the focal dystonia group was greater than normal and more similar to the generalized dystonia group during the late phases of the recovery curve. The average value of the localized late facilitation phase for the focal dystonia group was significantly greater than the control group and less than the generalized dystonia group. No differences were observed between groups for the average localized late inhibition phase of the recovery curve. CONCLUSIONS: Soleus H-reflex measures identified neurophysiologic differences between generalized dystonia, cervical dystonia and normal conditions. SIGNIFICANCE: This methodology enables analysis of the underlying characteristics of dystonic pathologies using soleus H-reflex methods rather than upper extremity H-reflex techniques.     

CADASIL or CADVaSIL?

In the present study, morphological examination of patients from two unrelated Polish families with CADASIL was performed. Using light microscopy, there were evident changes characteristic to the disease. On electron microscopy, deposits of granular osmiophillic material (GOM) were found not only in cerebral arteries and veins but also in cerebral capillaries and vessels of the internal organs. These findings indicate that pathological process in CADASIL is generalized and involves also small vessels devoid of smooth muscle cells. Therefore, we propose to consider a replacement for the name CADASIL that better reflects the morphological picture of the disease like, for example, cerebral autosomal dominant vasculopathy with subcortical infarcts and leukoencephalopathy (CADVaSIL) or, to preserve the commonly known acronym, cerebral autosomal dominant angiopathy with subcortical infarcts and leukoencephalopathy.     

Comparison of Sinemet CR4 and standard Sinemet: double blind and long-term open trial in parkinsonian patients with fluctuations

"Wearing-off" effect, the most common form of levodopa-induced fluctuations, seems to be related to the short plasma half-life of the drug. More sustained plasma levodopa levels may be achieved with a new controlled-release formulation of carbidopa/levodopa, Sinemet CR4. We studied 20 patients, 12 men and 8 women, with Parkinson's disease complicated by "wearing-off" phenomenon. Mean age was 61.1 +/- 8.1 years, duration of symptoms 8.3 +/- 2.4 years, and the Hoehn-Yahr stage 3.0 +/- 0.9. In a 12-week double-blind study, the average number of tablets administered per day decreased from 5.7 +/- 1.2 to 3.8 +/- 0.7 when Sinemet CR4 (50/200) was substituted for the standard Sinemet (25/100) (p less than 0.001). However, this was at the expense of reducing the "on" time (without dyskinesia) from 9.3 +/- 4.6 to 7.5 +/- 4.3 (p less than 0.05), although the total "on" time did not significantly change. In a long-term follow-up of 18 patients, the "on" time with dyskinesia and morning dystonia significantly increased (p less than 0.05). There was no significant change in the total daily dosage of levodopa, but the daily number of doses and tablets significantly decreased (p less than 0.001). Despite increased dyskinesia, most patients preferred taking fewer tablets and have elected to continue taking Sinemet CR4 instead of standard Sinemet. Sinemet CR4 seems to offer a new and effective strategy for the management of levodopa-related fluctuations.     

Über die Rolle von Makrophagen in der Pathogenität des Vacciniavirus für junge Ratten

Zusammenfassung Das Vacciniavirus vermehrt sich schnell in den Organen von 1 tägigen Ratten, und die Tiere verenden am 2. oder 3. Tag nach der Infektion. In den Organen von 7 tägigen Ratten kann sich das Virus anfangs vermehren, später wird es aber eliminiert und die Tiere überleben. Bei 15tägigen Ratten wird das Virus eliminiert und die Tiere verenden nicht.Eintägige Ratten, die vor der Infektion Makrophagen erwachsener Tiere erhalten haben, kamen nicht ad exitum. Die Makrophagen von erwachsenen Ratten haben im Gegensatz zu Makrophagen von jungen Tieren die Fähigkeit, das phagozytierte Virus zu inaktivieren.Es wird daraus der Schluß gezogen, daß für die hohe Empfindlichkeit junger Ratten gegenüber Vacciniavirusinfektionen die funktionelle Unreife ihrer Makrophagen verantwortlich ist.

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The role of macrophages in the pathogenicity of vaccinia virus for young rats

Summary Vaccinia viruses grew rapidly in organs of 1-day-old rats, and the animals died 2 or 3 days after infection. In the organs of 7-day-old rats the viruses replicated initially, but were later eliminated and the animals survived. The 15-day-old rats were capable of eliminating the viruses completely and did not die. When macrophages of adult animals were transferred to 1-day-old rats before infection the rats did not die. The macrophages of adult rats destroyed phagocytized viruses while those of young animals did not.The results suggest that this susceptibility of young rats to vaccinia virus infection is due to the functionally immature state of their macrophages.

     

Smoking as a risk factor for lung cancer and cardiac infarct as mediated by psychosocial variables. A prospective investigation

In 1965-66, a prospective psychosomatic investigation was started with 1,353 relatively old inhabitants of the village of Crvenka, Yugoslavia. The present article reports on the relevance of smoking for the incidence of lung cancer and cardiac infarct. The main results are: (1) The relevance of smoking is reduced, but not eliminated, by introducing psychosocial control variables, suggesting that the latter have direct influences both on smoking and on the diseases. (2) The relevance of smoking interacts very strongly with psychosocial background conditions: it is nearly reduced to zero when the latter are favorable, and is correspondingly high when they are unfavorable. The results are also interpreted in biochemical terms.