Brainstem involvement in obsessive-compulsive disorder.

We investigated the possible involvement of the brainstem in the pathology of obsessive-compulsive disorder. Brainstem auditory evoked potentials (BAEPs) were collected from a population of neurotics (100 patients), including a group of 50 subjects suffering from obsessive-compulsive disorder (OCD) and the rest having generalized anxiety disorder. Twenty-five, age- and sex-matched, healthy volunteers served as controls. BAEPs were recorded by standard techniques as recommended by the AEEGS Clinical Evoked Potentials Guidelines. A one-way analysis of variance and the Fisher least-significant difference test were used for statistical analysis of the data. After stimulation of the right ear, a significant increase of wave I-V interpeak latency was found in the two groups of patients as compared with that of controls. Moreover OCD patients had a significantly reduced amplitude of wave III when compared to that of the control group. Our electrophysiological data suggest a possible involvement of brainstem in OCD pathogenesis. We discuss our findings in relation to biochemical, anatomical and physiological alterations described in the literature for serotonin-dependent systems.

An electrophysiological study in obsessional compulsive disorders.

Recent anatomoclinical and neuroimaging studies have suggested a possible relation between obsessional compulsive disorders (OCD) and some brain damage, such as frontolenticular lesions, basal ganglia cavitations and local glucose metabolism impairment. A poor frontocaudal regulation of the left hemisphere and an autonomic nervous system dysfunction in OCD patients have been supposed. To absess these morphofunctional abnormalities, an electrophysiological approach has been performed in 100 consecutive neurotic patients, screened with various neuropsychological tests and divided in two groups, 50 with OCD and 50 with anxious neurosis (ANX). Patients were submitted to EEG spectral analysis and BAEP studies and comparated with 25 age-matched normal controls. The mean alpha power in occipital regions was significantly higher in OCD patients and reduced in ANX patients. A significant reduction of the beta activity was recorded in frontal regions in both patient groups as compared to controls. A slight (p < 0.11) increase in I-V interpeak latency (IPL) vs. control group was observed in BAEP from left ear. A significant increase of the same IPL in OCD vs. controls (p < 0.025) was observed in BAEP from right ear. A slight n.s. reduction in III wave amplitude in OCD patients was observed in BAEP from left ear, whereas a highly significant reduction in the same wave amplitude from BAEP from right ear was observed in OCD patients. The above findings cold be account for both a frontotemporal and brainstem dysfunction with a probable involvement of serotoninergic central pathways, with a significant impairment of pontine segment in ANX patients and of mesencephalic region in OCD patients.

Could migraine be a "protective factor" against tumors?

Patients with migraine headaches show significantly lower prevalence of malignant neoplasms when compared with the general control group or the age-matched control group. Conversely, no significant difference concerning the family history for neoplasms has been found between the two groups. Nevertheless, headache and cancer in a family member in migraneous are not coexistent. Although more extensive, epidemiological studies are necessary to confirm our data, it is suggested that some particular biochemical or psychologic aspects involved in the pathogenesis of migraine might represent the presence of a protective factor against neoplasm development.

The antimigraine effect of ergotamine: a role for alpha-adrenergic blockade?

The hypothesis that alpha-adrenergic receptor blockade accounts for the ability of ergotamine to stop migraine attacks was tested, in migraine patients, in an experimental migraine model based on nitroderivative- induced attacks. In a preliminary single blind, placebo controlled study, thymoxamine, a prevalently post-synaptic alpha adrenergic receptor antagonist, was able to abort migraine attack in 9 out of 10 patients, as opposed to 2 out of 10 by placebo (p < 0.005 Fisher's exact test). In a subsequent randomized, crossover, placebo controlled double blind study, the ability of a selective alpha-1 adrenergic receptor agonist, methoxamine, to block ergotamine antimigraine effect was studied. In 26 patients migraine was induced in two separate tests and then ergotamine was administered once after methoxamine pretreatment and once after placebo; methoxamine was significantly more effective than placebo in blocking antimigraine effect of ergotamine (p = 0.0055 Fisher's exact test). These results support the hypothesis that ergotamine alpha-1 adrenolytic properties may account for its antimigraine effect suggesting that this action takes place outside the blood-brain barrier, since methoxamine can cross it very poorly. Ergotamine target structure could be the trigeminal innervation of the extracranial and/or dural vessels.

Quantitative and qualitative modifications of lymphocyte subsets after sublingual administration of isosorbide dinitrate in migraineurs. Preliminary report.

In 22 migraine patients and 5 healthy controls an investigation has been performed on lymphocyte subsets in basal conditions and 90 minutes after sublingual isosorbide dinitrate (IDN) administration. In all patients the drug assumption induced a typical migraine attack with increase in all examined lymphocyte subsets with except of NK cells. A statistically significant increase (p < 0.05) in T lymphocyte subsets we found during the crisis, whereas in healthy controls neither a migraine attack nor any modification in lymphocyte subsets could be observed. These results seem to confirm the immune alteration we have previously found in migraineous patients and suggest the possible role of IDN-stimulated endothelium not only in vasodilatation but also in production of substances responsible of the observed immune modifications.

Derangement of the hypothalamic GnRH pulse generator in women with epilepsy.

An increased frequency of reproductive endocrine diseases has been described in women with epilepsy and a subclinical reproductive dysfunction has been suggested in normally menstruating epileptic women. We assessed the reproductive endocrine function in 11 normally menstruating, drug-free epileptic women, evaluating the basal hormonal profile and LH pulsatile secretion during continuous EEG monitoring. A significant LH hyperpulsatility was observed in epileptic women compared with controls; moreover, a significant increase of gonadotropin basal secretions was observed when inter-ictal paroxysmal activity increased. The derangement of the hypothalamic GnRH pulse generator may represent a subclinical condition associated with epilepsy, not necessarily affecting the regularity of menstrual function. However, it is possible that the alteration of LH pulsatile pattern might eventually cause reproductive endocrine diseases. Paroxysmal activity seems to be an important additional factor in the derangement of gonadotropin secretion.

Thymectomy for myasthenia gravis: predictive factors and long term evolution. A retrospective study on 46 patients.

Forty-six patients with myasthenia gravis (MG) underwent transternal thymectomy between 1975 and 1991 and were observed over a long term follow up period (mean 6 years). Surgery was well tolerated and was followed in 32.6% of patients by remission of symptomatology. The severity of symptoms according to the Osserman scale was significantly reduced: slight forms of myasthenia increased soon after thymectomy more frequently than moderate and severe forms. Response to thymectomy at 3 months, according to the Hankins scale, was found to be positive (remission or amelioration of symptoms) in 31/41 patients, and worse in patients with thymoma. Probability of clinical remission and death were both significantly correlated with clinical response at three months after thymectomy. No other preoperatory clinical factor (onset age, sex, initial severity of MG, interval from symptom onset to thymectomy) was found to predict the response to treatment. Preoperatory mediastinic CT had a good reliability (> 85%) in diagnosing thymona, but was rarely able to distinguish between thymic hyperplasia and atrophy.

Markers of activated T lymphocytes and T cell receptor gamma/delta+ in patients with multiple sclerosis.

We studied interferon-gamma (IFN-gamma), alpha-tumor necrosis factor (alpha-TNF) and granulocyte macrophage colony-stimulating factor (GM-CSF) in the cerebrospinal fluid and serum of 18 patients with multiple sclerosis (MS) and 10 subjects with other neurological diseases (OND). We also studied the cerebrospinal-fluid CD 69 expression, and T cells with T cell receptor (TcR) gamma/delta+. We found an increase of IFN-gamma (14.0 +/- 3.5 U/ml) and GM-CSF (8.0 +/- 3.4 pg/ml) levels in the cerebrospinal fluid of MS patients compared to the OND group (p < 0.005 and p < 0.01, respectively). The frequency of detectable cerebrospinal-fluid and serum alpha-TNF was similar in patients with MS and with OND. The cerebrospinal-fluid CD69 expression in lymphocytes was significantly higher in MS patients (15.0 +/- 9.9%) than in the control group (3.7 +/- 6.2%; p < 0.005). Comparable serum levels of IFN-gamma and GM-CSF were detected in patients with MS and in OND subjects. No significant difference in the incidence of TcR gamma/delta+ in the cerebrospinal fluid was found between the two groups. These results indicate an activation of T lymphocytes and macrophages in patients with MS. Our data do not suggest a role for an increased incidence of TcR gamma/delta+. However, we cannot rule out the possibility that these T cells could be present at the plaque site of MS patients.

Cerebrospinal fluid beta-2-microglobulin in multiple sclerosis and AIDS dementia complex.

Cerebrospinal fluid (CSF) and serum concentrations of beta-2-microglobulin (beta-2-m) were evaluated in 19 patients with clinically definite multiple sclerosis (MS), in 21 with AIDS dementia complex (ADC), and in 20 subjects with other neurological diseases (OND). CSF beta-2-m and CSF/serum beta-2-m ratio were significantly higher in the patients with ADC than in the MS and OND patients. The CSF and serum levels of beta-2-m in MS patients were not significantly different from those of OND patients. These findings indicate that CSF beta-2-m and CSF/serum ratio may be a useful marker in the diagnosis of ADC. In MS patients the beta-2-m CSF determinations are of no value.

A case of facio-scapulo-humero-peroneal myopathy with inflammatory changes. Preliminary data on distribution of mononuclear cells in muscle tissue.

We report the case of a 49 year old woman with clinical, electrophysiological and histochemical signs of facio-scapulohumeroperoneal dystrophy characterized by highly inflammatory changes. Lymphocyte typing by immunofluorescence and immunoperoxidase techniques on a muscle biopsy fragment revealed a large number of T8 cells at endomysial sites. There was no evidence of direct invasion of sound fibers by lymphocytes, which are thus unlikely to have exerted a primary cytotoxic action on the muscle tissue. Another finding was an increased number of macrophages in both endomysial and perivascular regions. Cell-mediated immunity did not play a significant role in the pathogenesis of our case, unlike other reported cases of polymyositis and facioscapulohumeral dystrophy with inflammatory findings.

Cerebrospinal fluid beta-2-microglobulin in HIV-1 infection, as a marker of neurological involvement.

Cerebrospinal fluid (CSF) and serum concentration of beta-2-microglobulin (beta-2-m) were evaluated in 30 patients in various stages of HIV-1 infection. CSF beta-2-m and CSF/serum ratio were significantly higher in patients with neurological complications respect to asymptomatic subjects. These findings indicate that CSF beta-2-m and CSF/serum ratio may be a useful marker of neurological involvement in HIV-1 infection.

Abnormal pattern of luteinizing hormone pulsatility in women with epilepsy.

Dysfunction of the hypothalamic-pituitary-ovarian axis in epileptic females has been suggested in the latest years. To further elucidate this issue, we assessed reproductive endocrine function in 10 normally cycling, drug-free epileptic women and in 5 normal controls, evaluating the basal hormonal profile and luteinizing hormone (LH) pulsatility in the midfollicular phase. Luteinizing hormone pulse frequency was significantly higher in epileptic women with a consequent reduction of the LH interpulse interval. We suggest that epilepsy may interfere with the functional activity of the gonadotropin-releasing hormone pulse generator. The pathogenetic mechanisms for this phenomenon may be the spreading of paroxysmal activity within the hypothalamic areas or, alternatively, a neurotransmitter dysfunction giving rise both to the seizure disorder and to the abnormal LH pulsatile pattern.

[Unilateral heterotropia of the cerebral cortex]. / Eterotopia unilaterale della corteccia cerebrale.

The case of a slight epileptic 30-year-old woman with heterotopic gray matter diagnosed by TC and NMR is described. The seizures of left jacksonian type begun at the age of 3, and stopped at the age of 12. In 1986 the seizures of atonic-akinetic type reappeared and continued until now at an average of 2 for year without obstacle for her job of employer. Cerebral computed tomography and magnetic resonance imaging showed a neuronal migration anomaly with nodular masses of gray matter in the right temporo-parietal area, characteristic image of gray matter heterotopia.

Exaggerated spontaneous release of tumor necrosis factor-alpha/cachectin in patients with migraine without aura.

Serum levels of tumor necrosis factor (TNF)-alpha/cachectin have been evaluated in 20 patients with Migraine without Aura (MwA) versus 17 patients with Chronic Type Tension Headache (CTTH). Results show an exaggerated release of TNF-alpha/cachectin in sera of patients affected by MwA, while in CTTH patients TNF serum concentration is comparable to that observed in normal donors. Some hypotheses are formulated in order to clarify the TNF-alpha/cachectin spontaneous production and its biological significance in patients with MwA.

[Possible mechanisms of the action of drugs for hemicrania]. / Possibili meccanismi di azione dei farmaci antiemicranici.

Different classes of drugs are used in the pharmacological treatment of headache, both during migraine crisis and migraine prophylaxis. How these drugs exert their therapeutical effect in migraine is not clearly understood. Hypothetical mechanisms of action are discussed by the Authors in regard to the different pathogenetical events relevant to migraine. It is proposed that different pathological events can be modified by one drug and, conversely, one mechanism of action may be common to different drugs.

Neurocutaneous melanosis, neurofibromatosis and spinal meningioma: an unusual association.

The case of 38-year-old woman bearer of a congenital giant naevus "en pélerine" with numerous neurofibromas and other satellite naevi was reported: the patient was afflicted by spastic tetraparesis, more pronounced on the right side. MRIscan of the spine revealed the presence of a cervical spinal tumor shown histologically to be a psammomatous meningioma. The skin picture was consistent with neurocutaneous melanosis; the rarity of its association with neurofibromatosis and spinal meningioma is discussed in the light of embryologic arguments.

Steroid-induced disappearance of primary central nervous system lymphoma. Clinical, neuroradiological and pathological findings.

A 73-year-old man presented a progressive neurologic syndrome with impairment of multiple cranial nerves, ataxia and limb weakness. Neuroradiological evaluation showed multiple supra and infratentorial lesions, which completely disappeared after steroid treatment on two occasions. These neuroradiological modifications were closely correlated with clinical picture and CSF findings. Post-mortem examination showed multifocal primary CNS immunoblastic large cell lymphoma. Immunohistochemistry showed that the tumor was of B-cell origin.