Somatosensory temporal discrimination in patients with primary focal dystonia.

PURPOSES: To determine whether somatosensory temporal discrimination will reliably detect subclinical sensory impairment in patients with various forms of primary focal dystonia. METHODS: The somatosensory temporal discrimination threshold (STDT) was tested in 82 outpatients affected by cranial, cervical, laryngeal and hand dystonia. Results were compared with those for 61 healthy subjects and 26 patients with hemifacial spasm, a non-dystonic disorder. STDT was tested by delivering paired stimuli starting with an interstimulus interval of 0 ms followed by a progressively increasing interstimulus interval. RESULTS: STDT was abnormal in all the different forms of primary focal dystonias in all three body regions (eye, hand and neck), regardless of the distribution and severity of motor symptoms. Receiver operating characteristic curve analysis calculated in the three body regions yielded high diagnostic sensitivity and specificity for STDT abnormalities. CONCLUSIONS: These results provide definitive evidence that STDT abnormalities are a generalised feature of patients with primary focal dystonias and are a valid tool for screening subclinical sensory abnormalities.

Tactile temporal discrimination in patients with blepharospasm.

BACKGROUND: Blepharospasm is an adult-onset focal dystonia that causes involuntary blinking and eyelid spasms. Studies have shown the presence of sensory deficits associated with dystonia. AIM: To rule out any confounding effect of muscle spasms on sensory performance in affected and unaffected body regions of patients with blepharospasm and with hemifacial spasm. METHODS: Participants (19 patients with blepharospasm, 19 patients with hemifacial spasm and 19 control subjects) were asked to discriminate between two stimuli that were either simultaneous or sequential (temporal discrimination threshold, TDT). Pairs of tactile stimuli were delivered with increasing or decreasing inter-stimulus intervals from 0 to 400 ms (in 10-ms steps) to the hands or on the skin over the orbicularis oculi muscle. RESULTS: Tactile stimuli elicited similar TDTs in control subjects and patients with hemifacial spasm, but significantly higher TDTs in patients with blepharospasm, regardless of whether stimuli were applied to the orbicularis muscle or the hand. CONCLUSIONS: As TDT was abnormal in unaffected body regions of patients with blepharospasm, and patients with hemifacial spasm processed tactile stimuli normally, TDT deficits in blepharospasm depend on central rather than peripheral factors. This study further supports the link between focal dystonia and impaired temporal processing of somatosensory inputs.

Adrenal dysregulation in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a chronic progressive neuromuscular disorder of unknown etiology, characterized by weakness, muscle wasting, fasciculations and increased reflexes, with conserved intellect and higher function. The disease is due to degeneration of the motor neurons in the cerebral cortex, brainstem nuclei and anterior horns of the spinal cord. Although ALS poses an extreme burden on individual condition, data are missing concerning the regulation of adrenal function in the disease. In the present study we investigated cortisol levels in saliva of ALS patients as compared to healthy subjects. The results showed the loss of circadian rhythm of cortisol levels in ALS; in particular, levels of cortisol in the evening sample were significantly increased in ALS patients with respect to controls. Moreover, ALS patients did not show any physiological increase of cortisol levels following an unexpected mild stress (color-word Stroop test). These findings indicate the dysregulation of adrenal activity in the disease.

Behavioral sensitization to heroin by cannabinoid pretreatment in the rat.

The behavioral consequences of acute heroin challenge (0.5 mg/kg, s.c.) were measured in rats previously submitted to repeated administration of increasing doses of the synthetic cannabinoid receptor agonist, R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo-[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl) methanone mesylate (WIN55212.2) (first day 2 mg/kg, second day 4 mg/kg, third day 8 mg/kg) or vehicle. Heroin administration to rats pretreated with vehicle produced catalepsy. The same dose of heroin in WIN55212.2-pretreated rats was followed by a marked increase of locomotor activity with stereotyped and non-stereotyped behaviors. These effects were blocked by the opioid receptor antagonist, naloxone. These findings indicate that pretreatment with WIN55212.2 produces cross-sensitization to heroin in the rat. These changes might reflect long-lasting changes of receptor population or transcriptional mechanisms in the mesolimbic system.

Behavioral sensitization to WIN55212.2 in rats pretreated with heroin.

There is evidence of similarities and interactions between central opioid and cannabinoid system with reference to drug reinforcement and abuse. Here we demonstrate that repeated injection of heroin produces behavioral sensitization towards administration of the synthetic cannabinoid receptor agonist WIN55212.2 in the rat. These effects were blocked by both the cannabinoid antagonist SR141716A and the opioid antagonist naloxone. These findings suggest that repeated exposure to heroin produces neuroadaptative changes in brain circuits that contribute to mediate the behavioral consequences of acute administration of WIN55212.2. The present results expand our knowledge on the interactions between central opioid and cannabinoid systems with respect to drug abuse.

Effects of intra-VTA injection of neurotensin on local cerebral glucose utilization in freely moving rats.

The [14C]2-deoxyglucose method was applied to measure the effects of the injection of neurotensin (7 microg) in the ventral tegmental area on local cerebral glucose utilization in the rat. Injection of neurotensin produced significant increases of glucose utilization in the shell of the nucleus accumbens and in the olfactory tubercle. These results indicate that stimulation of neurotensin receptors in the ventral tegmental area produces functional changes that are confined to the regions receiving mesolimbic projections within the rostral extended amygdaloid complex. These findings extend our understanding on the effects of neurotensin in the limbic system, with particular regard to reward pathways.