Molecular markers of gliomas: a clinical approach.

Over the last decade, the knowledge on the molecular genetic background of gliomas has dramatically increased. This information provides the basis for the molecular target therapies and molecular tests serve to complement the subjective nature of histopathologic criteria and add useful data regarding response to treatments and prognosis. In particular, the use of loss of heterozygosity (LOH) and methylation specific polymerase chain reaction (PCR) (MSP) based testing of gliomas is already in place and used clinically in several centers. This paper provides a brief overview of these molecular genetic aberrations and discusses the clinical utility, as well as the advantages and disadvantages of such approach. Newly developed molecular techniques, such as LOH testing, fluorescence in situ hybridization (FISH), DNA sequencing and MSP, are currently being employed in assessment of gliomas in some laboratories. However, the clinical use of some markers and the context in which the information obtained should be used are still not entirely understood. Therefore, this paper will focus on validation and implementation of molecular testing in gliomas, with emphasis on LOH on chromosomes 1p, 19q, 17p and 10q and O(6)-methylguanine-DNA methyltransferase (MGMT) methylation status.

Abnormal head nociceptive withdrawal reaction to facial nociceptive stimuli in Parkinson's disease.

INTRODUCTION: Trigemino-cervical-spinal reflexes (TCSRs) are complex brainstem stereotyped nociceptive responses involved in a defensive withdrawal reaction of the head from facial nociceptive stimuli. OBJECTIVE: The present study was undertaken to collect data on possible TCSR abnormalities in idiopathic Parkinson's disease (PD) and investigate any correlation with motor signs and L-DOPA administration. METHODS: TCSRs were registered from the semispinalis capitis and biceps brachii muscles after electrical stimulation of the supraorbital nerve in 18 patients with PD and 24 controls. The latency (L) and area (A), as well as the sensory (ST), painful (PT) and reflex (RT) thresholds were measured during the 'off' and 'on' state, and possible correlations with the UPDRS III total score, selected subscores (tremor, neck rigidity, upper limb rigidity, akinesia, rising from a chair, posture and posture instability) and duration of illness were investigated. RESULTS: Significant changes between controls and PD patients were found in the L, A, PT and RT of TCSRs. These results were not significantly influenced by L-DOPA treatment. A significant correlation was found between neck rigidity, postural instability scores and duration of illness and the TCSR L and A values in PD patients in the 'off' state. CONCLUSIONS: TCSRs abnormalities, combined with dopamine resistance, are consistent with a primary loss of brainstem neurons mediating a complex sensory-motor integration including neck muscle tone and postural control as well as the head withdrawal reaction to the nociceptive stimuli. SIGNIFICANCE: TCSRs may represent a useful tool for the assessment of brainstem sensory-motor function in PD as well as other movement and degenerative disorders.

Mutations of ANT1, Twinkle, and POLG1 in sporadic progressive external ophthalmoplegia (PEO).

To verify the impact of mutations in ANT1, Twinkle, and POLG1 genes in sporadic progressive external ophthalmoplegia associated with multiple mitochondrial DNA (mtDNA) deletions, DNA samples from 15 Italian and 12 British patients were screened. Mutations in ANT1 were found in one patient, in Twinkle in two patients, and in POLG1 in seven patients. Irrespective of the inheritance mode, screening of these genes should be performed in all patients with progressive external ophthalmoplegia with multiple mtDNA deletions.

RR interval variation, sympathetic skin reflex and QT dispersion in the assessment of autonomic function in peripheral neuropathy.

In recent years, two simple non-invasive tests, sympathetic skin response (SSR) and RR interval variation (RRIV) have been used to assess autonomic function (Wang et al., 1994; Drory et al., 1995; Chassande et al., 1996; Bordet et al., 1996; Spitzer et al., 1997). Their easy performance by an electromyographic (EMG) machine and successful clinical correlation (Shahani et al., 1990) have made them routine in autonomic assessment in several EMG laboratories. More recently QT dispersion on electrocardiogram (ECG) has been shown to have increased in patients with diabetic neuropathy and several autonomic dysfunctions (Wei et al., 1995; Lengyel et al., 1997; Langen et al., 1997; Axelrod et al., 1997). In order to evaluate the diagnostic value of the RR interval variation, sympathetic skin response and QT dispersion combined, we performed the three tests on a group of 37 patients with several peripheral neuropathies with and without clinical signs of dysautonomia. All patients were studied using an electromyograph (EMG). The results of the SSR, RRIV and QT dispersion combined have shown abnormal values in all patients with neuropathy and clinical dysautonomia and in some patients without clinical signs of dysautonomia, suggesting a subclinical autonomic dysfunction. The principal finding of this study is that the evaluation of the RRIV, SSR and QT dispersion combined may contribute to the assessment of dysautonomia in patients with somatic neuropathy and that they may be currently performed by an electromyograph.