Clinical and genetic heterogeneity as well as influence of environmental factors have hampered identification of the genetic factors which are involved in episodic diseases such as migraine, episodic ataxia and epilepsy. The study of rare, but clearly genetically determined subtypes, may help to unravel the pathogenesis of the more common forms. Recently, different types of mutation in the brain-specific P/Q type calcium channel alpha 1A subunit gene (CACNA1A) on chromosome 19p13 were shown to be involved in three human disorders: familial hemiplegic migraine (FHM), episodic ataxia type 2 (EA2), and chronic spinocerebellar ataxia type 6 (SCA6). In addition, evidence is accumulating that the same gene is also involved in the common forms of migraine with and without aura. In the tottering and leaner mouse, which are characterised by epilepsy and ataxia, similar mutations were identified in the mouse homologue of the calcium channel alpha 1A subunit gene. These findings add to the growing list of episodic (and now also chronic) neurological disorders, which are caused by inherited abnormalities of voltage-dependent ion channels. The findings in migraine illustrate that rare, but monogenic variants of a disorder, may be successfully used to identify candidate genes for the more common, but genetically more complex, forms.

Animals↗

PubMedDate not supplied

Blood damage, platelet and clotting activation during application of radiofrequency or cryoablation catheters: a comparative in vitro study.

During catheter ablation of cardiac tissue, the insulting stimulus may damage and activate the blood. Specifically activation of platelets and the clotting system is a potential risk by their formation of thrombi. In this study the effect of two different techniques, a radiofrequency and a cryo-application procedure, on the activation of platelets and clotting in an in vitro blood circulation model was investigated. The radio-frequency procedure induced significantly more blood cell damage, platelet activation and clotting than did the cryo-application procedure. Macroparticles were circulating in blood after the radiofrequency procedure. In the cryo procedure, blood damage was limited to the frozen blood spherule around the tip of the catheter. It is concluded that at least in those circumstances where blood is directly contacting the tip of the radiofrequency or cryo-application catheter, the latter is more safe with regard to thrombus formation.

Blood Cells↗

PubMedDate not supplied

Cardiovascular safety of lubeluzole (Prosynap(R)) in patients with ischemic stroke.

The cardiovascular safety of lubeluzole was evaluated in patients with ischemic stroke in a double-blind, placebo-controlled trial. Forty-six patients were randomized to receive a continuous daily infusion of lubeluzole 5 mg (loading dose 3.75 mg over 1 h), lubeluzole 10 mg (loading dose 7.5 mg over 1 h), or placebo for 5 days within 24 h of stroke onset. The primary measure of cardiovascular safety was the QTc interval, derived from the continuous electrocardiogram (ECG) and measured during treatment and a 2-day follow-up. Compared with placebo. Neither dosage of lubeluzole had any statistically or clinically relevant effects on the QTc. Neither were there any significant differences among the three treatment groups in the area under the curve for heart rate, QT interval, QT dispersion, or QTlc. Lubeluzole did not increase the frequency of ECG abnormalities. No ventricular fibrillation, ventricular tachycardia, or torsades de pointes were observed in any of the treatment groups. During this trial, 3 patients in the placebo group and 2 patients in the lubeluzole 5-mg group died. There were no deaths in the lubeluzole 10-mg group. Adverse experiences were similar in all three treatment groups except that superficial thrombophlebitis was more frequent in the lubeluzole 10-mg group. In doses to 10 mg/day, lubeluzole has a favorable cardiovascular safety profile, as demonstrated by the lack of clinically relevant effects on heart rate, QT, QTc, and QTlc, and it was well tolerated by patients with ischemic stroke.

Acute Disease↗

PubMedDate not supplied

Clinical aspects of cerebral amyloid angiopathy.

Amyloid depositions mainly consist of proteins with a fibrillary structure. A large number of different proteins have amyloidogenic properties. Amyloids are now categorized on the basis of their chemical structure, but the clinical classification of localized and systemic amyloid is still useful. The proteins that can be found in cerebral amyloid angiopathy are cystatin C, beta/A4 and transthyretin. Cerebral amyloid angiopathy can remain symptom-free, but can also give a broad spectrum of clinical and radiological manifestations, including (vascular) dementia, cerebellar and cerebral hemorrhage, subarachnoid hemorrhage, and leukoencephalopathy. It is debated whether amyloid angiopathy plays a causative role in Alzheimer's disease, but it is strongly correlated with the presence of cerebral plaques. In this review, the clinical spectrum of cerebral amyloid angiopathy will be described, based on retrospective studies from the literature. Hereditary cerebral hemorrhage with amyloidosis (Dutch) will be presented as a 'prospective' model to study the clinical effects of amyloid angiopathy.

Cerebral Amyloid Angiopathy↗

PubMedDate not supplied

Investigation of gait in elderly subjects over 88 years of age.

To evaluate senile gait patterns in octagenarians and nonagenarians, we provided a standardized questionnaire on gait disabilities to 153 elderly subjects over 88 years of age. Subjects represented a relatively healthy subgroup of noninstitutionalized residents who participated in a gerontological survey of all inhabitants of the city of Leiden who were 85 years of age or older. Of the 142 subjects who responded to this questionnaire, 87 persons (61%) claimed distinct diseases as a cause of gait impairment. Forty-two of the remaining 55 persons were investigated neurologically and received a standardized assessment of gait. Twenty-five persons (18% of all responders) had a completely normal gait, whereas a wide spectrum of gait abnormalities--mainly with ataxic features--was encountered in the remaining persons. It is concluded that a surprisingly high number of very old community residents can have a completely normal gait. Gait disorders in this age group are most frequently associated with common distinct diseases. In addition, many elderly have a gait disturbance of variable clinical nature and unclear pathologic basis, which may represent the "idiopathic senile gait."

Aged↗

PubMedDate not supplied

MR imaging in multiple sclerosis: comparison with clinical, CSF, and visual evoked potential findings.

MR examinations of 136 patients with multiple sclerosis (MS) were evaluated to correlate the results with clinical, CSF, and visual evoked potential (VEP) findings. In addition, 22 of the 136 patients were studied several times during a 5-month follow-up period. It was demonstrated that MR is superior to CSF and VEP findings in establishing cerebral alterations in MS. A relationship between the results of CSF and VEP examinations and the MR results could not be detected. Negative CSF and VEP results corresponded to positive MR imaging and vice versa. In our series, five negative MR results were obtained in patients with clinically proved MS. The extent of alterations shown up by MR corresponds to the duration of the disease; in particular, more confluent abnormalities in the periventricular region were found in patients with long-standing disease. More plaques were found in patients with a primary relapsing/remitting course of the disease than with the primary chronic progressive form. The clinical course and the grade of disability did not correspond to differences in MR imaging. Follow-up demonstrated that most lesions remain unchanged (72-79%); increases and decreases in the size of the plaques seem to depend on the clinical course. These results suggest that MR is the most sensitive technique for establishing the diagnosis of MS.

Evoked Potentials, Visual↗

PubMedDate not supplied

[Epilepsies and epileptic attacks in the elderly].

Epilepsies and epileptic seizures seldom occur firstly in aged people. Clinically these seizures are not different from those of children, adolescents and younger adults, except from pycnoleptic petit-mal almost never manifestating firstly in the elderly. If etiologic factors often remain unknown, cerebral tumors, even if they are rare, must always be suspected. Cerebro-vascular and cerebro-metabolic diseases, head injuries, abuse of alcohol, and medicaments may be responsible for the first manifestation of epileptic seizures in the aged. Degenerative brain diseases sometimes are responsible for epileptic seizures and epilepsies in elderly people. But even if an epileptic seizures is insured, metabolic diseases (e.g., hypoglycemia) or heart diseases must be considered, because they may lead eventually to the manifestation of epileptic seizures.

Aged↗

PubMedDate not supplied

[Sumatriptan in clinical practice].

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Animals↗