L. Rampello

Pregabalin in the treatment of chronic pain: An overview

Chronic ‘pathological’ pain is sustained by mechanisms of peripheral and central sensitization, which are being increasingly investigated at the molecular and cellular levels. The molecular determinants of nociceptive sensitization are natural targets for potential analgesic drugs used in the treatment of different forms of pain. Most of these determinants are common to all forms of chronic pain, and it is therefore not surprising that drugs specifically targeted for the treatment of neuropathic pain are effective in relieving nociceptive inflammatory pain and vice versa. The molecular mechanisms of sensitization that occur in peripheral nociceptors and the dorsal horns of the spinal cord are putative targets for context-dependent drugs, i.e. drugs that are able to discriminate between ‘normal’ and ‘pathological’ pain transmission. Among these, pregabalin and gabapentin bind to the α2δ subunit of voltage-sensitive Ca2+ channels, which sustain the enhanced release of pain transmitters at the synapses between primary afferent fibres and second-order sensory neurons under conditions of chronic pain. Pregabalin in particular represents a remarkable example of a context-dependent analgesic drug that acts at a critical step of nociceptive sensitization. Preclinical and clinical data suggest that pregabalin is more than a structural and functional analogue of gabapentin and may be effective in the treatment of nociceptive inflammatory pain that is resistant to gabapentin.

Trazodone therapy of the post-stroke depression

The incidence of depression following a hemispheric stroke ranges from 25 to 60%. The benefit of antidepressant therapy on the outcome of rehabilitation in the subacute post-stroke phase is well known. We studied subjects both with and without evidence of depression, as indicated by any one of three criteria: (i) Clinical diagnosis of depression, (ii) Abnormal Zung-depression score. (iii) Abnormal dexamethasone suppression test (DST). Patients in a stroke rehabilitation program (22) were randomized to receive either placebo or 300 mg/day trazodone-HCl, beginning 30 days after the stroke. Patients with either a clinical diagnosis of depression or abnormal Zung depression scores showed a consistent trend towards greater improvement in Barthel activities of daily living (ADL) scores, with antidepressant therapy, as compared to patients receiving placebo. An abnormal DST was associated with significant improvement in the ADL scores in subjects receiving trazodone, i.e., in post-stroke depression such a treatment seems to be beneficial.

The conditioned eyeblink reflex: A potential tool for the detection of cerebellar dysfunction in multiple sclerosis

The delayed conditioned eyeblink reflex, in which an individual learns to close the eyelid in response to a conditioned stimulus (e.g. a tone) relies entirely on the functional integrity of a cerebellar motor circuitry that involves the contingent activation of Purkinje cells by parallel and climbing fibres. Molecular changes that disrupt the function of this circuitry, in particular a loss of type-1 metabotropic glutamate receptors (mGlu1 receptors), occur in Purkinje cells of patients with multiple sclerosis and in mice with experimental autoimmune encephalomyelitis as a result of neuroinflammation. mGlu1 receptors are required for cerebellar motor learning associated with the conditioned eyeblink reflex. We propose that the delayed paradigm of the eyeblink conditioning might be particularly valuable for the detection of subtle abnormalities of cerebellar motor learning that are clinically silent and are not associated with demyelinating lesions or axonal damage. In addition, the test might have predictive value following a clinically isolated syndrome, and might be helpful for the evaluation of the efficacy of drug treatment in multiple sclerosis.

Effects of Hyper- and Hypoprolactinemia on Glutamate Decarboxylase Activity in Medial Basal Hypothalamus of Male Rat

Haloperidol, sulpiride, domperidone and apomorphine, drugs which influence dopamine (DA) receptors and in turn prolactin (PRL) secretion have been shown to induce parallel changes in medial basal hypothalamic (MBH) glutamate decarboxylase (GAD) activity and serum PRL levels. The possibility that PRL may be involved in the effects of the drugs on MBH GAD activity is suggested in view of the evidence that hypophysectomy completely prevents drug-induced MBH GAD activity changes and that hyperprolactinemia by anterior pituitary homograft results in a significant, although small, change in the enzymatic activity.

When the word doesn't come out: A synthetic overview of dysarthria

Motor speech disorders are common in a number of neurological conditions including diseases involving impairment of the pyramidal, extrapyramidal, and cerebellar pathways, cranial nerves, muscular apparatus, neuromuscular plaque, and of cognitive, symbolic and mnestic activities. The diagnosis of speech disorders, namely the dysarthrias, involves the assessment of characteristic structural cerebral, prosodic, phonetic and phonemic changes, often flanked by concomitant functional, clinical, neuroradiological, neurophysiological and behavioral impairment. This paper presents a brief outline of the most significant associations to facilitate prompt differential diagnosis and thereby reduce the number of instrumental examinations required for diagnostic testing.

FLUNARIZINE AND ESSENTIAL TREMOR IN THE ELDERLY

Flunarizine (FZ) is a selective calcium channel blocker used in the therapy of migraine and vertigo. FZ and its parent compound cynnarizine (CZ), may cause movement disorders similar to those observed with neuroleptics, including orofacial dyskinesia, Parkinsonism and postural tremor. A recent report showed that the FZ improves essential tremor (ET); therefore we studied the effects of FZ in 12 patients with moderate to severe ET. Tremor was evaluated after 8 weeks of treatment and was assessed in relation to disability in areas of dressing, writing, eating and drinking. FZ was initially administrated in a dose of 5 mg, in the evening, and after ten days it was increased to 10 mg, and continued for a 7 week period. No changes were made in concurrent medications during the study. It was observed that FZ is an ineffective drug in moderate to severe ET and may worsen the symptoms in some patients. The results of our study exclude the use of FZ in the treatment of ET, especially in elderly patients.

Left temporal glioblastoma presenting with the involvement of selective memory: a case report.

Glioblastoma multiforme, the most malignant and frequent glioma [1], is found more frequently in the left hemisphere [2,3] and produces symptoms by a combination of focal neurological deficits. We describe the case of a 65-year-old man admitted, with a diagnosis of TIA made in another department, after appearance of recurring episodes of selective amnesia, initially concerning only the remembrance of familiar numbers (such as his own telephone number or address number, etc.) and lately regarding other numbers, dates and names. A neuropsychological battery was performed in order to evaluate patient’s cognitive functions. The Mini Mental State Examination [5], Constructive apraxia test [6], Trail Making Test (TMT A,B) [7] and Raven Coloured Progressive Matrices [8] did not point out abnormalities of visual and spatial abilities, attention, recognition of numbers and letters, visual research, motor velocity and motor coordination, control and executive functions, and set shifting and problem solving abilities. Verbal supraspan learning test [6] was performed to analyse the memory’s functions. The total number of words recalled from Long-Term Memory (LTM) was 31 (corrected for patient’s age and years of school 1⁄4 29; equivalent score (ES) 1⁄4 0), that was below normal for patient’s age and years of school. The total number of words not casually recalled from Long-Term Memory (LTM) was 2 (corrected=0; ES=0), that was below normal. The number of words recalled after 5 min from Long-Term Memory (LTM) was 2 (corrected 1⁄4 1.75; ES 1⁄4 0), that is under the normal range. Verbal fluency for semantic category test [9] was performed to evaluate the patient’s language-output abilities; the recall of words from lexical memory was 22 (corrected score= 26; ES=1), that was border-line. Memory complaint questionnaire (MAC-Q) [10] was administered for a subjective patient’s evaluation of memory functions and the score was 30, that was above normal score (<25). MAC-Q showed a severe impairment indicated by patient in the remembrance of familiar numbers (such as his own telephone number or frequently used postal codes, address and telephone numbers). We did not observe any other neuropsychological disorders. The objective neurological examination did not point out any clinically evident deficiency. The cardiologic examination revealed arterial hypertension of 2nd degree. The ecocolordoppler showed plaques in both the carotid axes and a stenosis of left internal carotid above 30%. MRI showed a roundish area not homogeneously hypointense in T1-weighted scans (Figure 1) and hyperintense in T2 weighted scans (Figure 2). This area was located in the left temporal lobe, and became soaked with the means of contrast. Electroencephalography (EEG) revealed slowing on the left temporal derivations. The patient was transferred to the department of neurosurgery, where he underwent an operation of removal. The histological examination pointed out the presence of GBM. This case of unusual memory disorder, selective for numbers, names and dates is an original manifestation of clinical–neurological expressiveness of a glioblastoma of the left temporal lobe. As a result, a clinical picture characterised by neuropsychological deficits (of all or some of the superior cognitive functions), imposes the differential diagnosis also with neoplastic disorders, whose premonitory symptoms, even in absence of objective neurological disorders, may be represented by selective deficits concerning the expressive forms of language and the memory.

Psychotic complications of long term levodopa treatment of Parkinson's disease

Psychotic symptoms such as hallucinations, delusions and confusion are well known side-effects of levodopa (LD) therapy of Parkinsons disease (PD), even if there is much confusion regarding the variability of the psychotic manifestations. We studied 18 patients clinically treated with LD associated with an inhibitor of peripheral aminoacid decarboxylase (DI). Daily dosage of LD ranged between 250 and 1750 mg; the mean age of patients was 72.7 years; the age at the onset of the disease was 63.3 and duration of the disease 8.4 years. In all patients any possible etiology of Parkinsonism were excluded. Brain CT scan excluded focal lesions in all cases. Psychotic complications were seen in 8 patients: using DSM-III-R-criteria, the various LD-induced psychotic states can be classified in two groups: simple (including or hallucinations with preserved insight) and complex ones (including chronic confusion without preserved insight). Patients with complex symptoms were younger at the onset of the disease and they developed these symptoms later, and these patients were also more susceptible to dyskinesias developed before psychotic complications.