Amitriptyline in the treatment of headache in patients with Parkinson's disease: a double-blind placebo-controlled study.

We evaluated the effect of 25 mg bid amitriptyline on muscle contraction headache in 36 patients with Parkinson's disease in a randomized double-blind placebo-controlled study. Treatment lasted 12 weeks, and we assessed the efficacy by number of days with headache, sum-of-severity score (intensity X number of days with headache), and consumption of analgesics. We also administered Hoehn-Yahr staging, the Webster Rating Scale, the Mini-Mental State, and the Zung Self-Rating Depression Scale. We assessed the patients after a 4-week run-in period and after 4, 8, and 12 weeks of treatment. Thirty-one patients (15 in the amitriptyline group and 16 in the placebo group) completed the trial. Amitriptyline reduced the intensity and the frequency of headache, whereas the placebo did not. The Zung Depression Scale and the Webster Rating Scale findings remained unchanged.

Cerebrospinal fluid cytokines in AIDS dementia complex.

We evaluated cerebrospinal fluid (CSF) and serum concentrations of interleukin-1-alpha (IL-1-alpha), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) in 30 patients with AIDS dementia complex (ADC), and in 20 HIV-seronegative subjects with other neurological diseases (OND). CSF TNF-alpha, IL-1-alpha and IL-6 were more frequently detectable in ADC patients than in OND subjects. These cytokines were also detectable in CSF of ADC patients with minimal symptoms. In contrast, the majority of both ADC and OND patients did not contain detectable serum levels of cytokines. Our data support the notion of intrathecal synthesis of cytokines in ADC patients and raise the possibility that activated macrophages may play a significant role in the pathogenesis of ADC.

Soluble interleukin-2 receptor and soluble CD8 molecules in cerebrospinal fluid and serum of patients with multiple sclerosis.

The purpose of this study was to analyse soluble interleukin-2 receptor (sIL-2R) and soluble CD8 (sCD8) molecules in the cerebrospinal fluid (CSF) and serum of 18 patients with definite multiple sclerosis (MS) and of 16 with noninflammatory neurologic diseases (NIND). All MS patients suffered from an exacerbation of the relapsing-remitting form of the disease within one month before examination. The mean serum levels of sIL-2R and sCD8 in the MS patients were not significantly different from those of NIND patients. Only one patient with MS had detectable sIL-2R in the CSF. CSF sCD8 was detectable in 10 of 18 MS patients and in 1 of 16 NIND patients. Our data indicate that the CSF and serum sIL-2R concentrations do not correlate with the disease activity. Conversely, increased levels of sCD8 only in the CSF of MS patients support the hypothesis of an intrathecal activation of CD8+ cells in MS. We think that CSF sCD8 can be a useful marker for the presence of activated T cells in the central nervous system.

Interictal depression in epilepsy.

The relation between depression and epilepsy was evaluated in 96 epileptic out-patients. We found that 50% of epileptic patients fulfilled the DSM-IIIR criteria for depression. The Hamilton Rating Scale for Depression, the Beck Self Depression Inventory and the Zung Anxiety Scale were also used in all patients. The patients with partial seizures with complex semiology (CPS) were more depressed than the patients with primary generalized epilepsy and with partial seizures with elementary semiology. A significant increase in the level of anxiety was also found in the group with CPS compared to the other two groups. No correlations were noted between severity of depression and duration of epilepsy, seizure frequency, socio-economic status, education, and family history of depressive illness. No relationship was observed between anticonvulsant drug levels and depression. We failed to confirm an association between side of epileptic lesion and severity of depression. We suggest that depression in epileptic patients does not represent a psychological reaction to a particular cognitive or physical impairment, but is in some way related to the type of epilepsy.

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.

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.

Possible role of transforming growth factor-beta in relapsing-remitting multiple sclerosis.

Cerebrospinal fluid (CSF) and serum levels of transforming growth factor (TGF)-beta and soluble intercellular adhesion molecule-1 (sICAM-1) were evaluated in ten patients with definite multiple sclerosis (MS) of the relapsing-remitting type. CSF TGF-beta levels of MS patients in remission were significantly (p < 0.01) higher than of MS patients in active phase, and there was a significant inverse correlation (p < 0.05) between TGF-beta and slCAM-1 levels in the CSF of patients in both remitting and relapsing type. This is consistent with a possible down-regulation of TGF-beta on ICAM-1 expression and suggests a possible synthesis in the central nervous system of TGF-beta.

Cerebrospinal fluid T cell receptor gamma/delta+ lymphocyte subsets in patient with AIDS-dementia complex.

A subset of peripheral T cells, whose physiological function is little known, expresses a distinct CD3-associated receptor composed of gamma and delta chains. We used two monoclonal antibodies to characterize the TcR gamma/delta lymphocytes (TcR delta 1+) and their fraction (TcS delta 1+) in peripheral blood and cerebrospinal fluid of patients affected by AIDS dementia complex (ADC). Thirty patients with ADC and a control group of twenty individuals with other non-inflammatory neurological diseases (OND) were recruited. Our results demonstrate that the TcR gamma/delta cells were also present in cerebrospinal fluid of ADC patients, but we did not find any statistical difference between the two groups.

No effect of cloricromen on some coagulation parameters in patients with ischaemic cerebrovascular disease.

Cloricromen is a new drug that inhibits platelet aggregation in man and in experimental thrombosis. Twenty patients with a history of atherothrombotic stroke received cloricromen (100 mg, twice daily) for 30 days in order to evaluate its effects on plasma fibrinogen, antithrombin III, and other variables of the haemostatic system. A statistically significant decrease in the prothrombin time (P < 0.01) was found only after 30 days of therapy. This decrease was transient and disappeared 15 days after the end of treatment. No statistically significant changes in plasma fibrinogen levels, antithrombin III, partial thromboplastin time, or platelet count were observed compared with baseline values. No side-effects were reported. This study did not reveal an effect of cloricromen on coagulative variables in patients with cerebrovascular occlusive disease.

Interleukin-6 and granulocyte macrophage-CSF in the cerebrospinal fluid from HIV infected subjects with involvement of the central nervous system.

We detected the cytokines interleukin-6 (IL-6) and granulocyte macrophage-CSF (GM-CSF) by ELISA in the CSF and serum of 30 HIV-infected patients classified as AIDS dementia complex (ADC), and 20 subjects with other neurological diseases (OND). We have found a high incidence of detectable IL-6 and GM-CSF in the CSF of ADC patients compared with OND patients. No statistical differences were observed between both groups for serum IL-6 and GM-CSF levels. These results suggest an intrathecal synthesis of these cytokines and a possible involvement in the pathogenesis of ADC.

Vascular smooth muscle cell dysfunction in patients with migraine.

BACKGROUND: Migraine is associated with increased risk of cardiovascular disease, but the mechanisms are unclear. OBJECTIVE: To investigate the activity of endothelial and vascular smooth muscle cells (VSMCs) in patients with migraine. METHODS: Case-control study of 12 patients with migraine without aura and 12 matched healthy control subjects. Endothelial and VSMC components of vascular reactivity were explored by plethysmography measurement of forearm blood flow (FBF) during infusions of vasoactive agents into the brachial artery. Forearm production of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) was also quantified. RESULTS: In patients with migraine, the vasodilating effect of acetylcholine (ACh), an endothelium-dependent vasodilator, was markedly reduced (p < 0.001 by analysis of variance). In response to the highest dose of ACh, FBF rose to 8.6 +/- 2.2 in patients with migraine and to 22.7 +/- 3.0 mL x dL(-1) x min(-1) in controls (p = 0.001). The dose-response curve to nitroprusside, a vasodilator directly acting on VSMCs, was depressed in patients with migraine (p < 0.001 by analysis of variance). The maximal response of FBF to nitroprusside was 12.1 +/- 2.0 in patients with migraine and 24.1 +/- 1.8 mL x dl(-1) x min(-1) in controls (p < 0.001). During ACh infusion, NO release from the endothelium was similar in patients and controls. In contrast, there was a marked release of cGMP from VSMCs in controls, but not in patients with migraine (-1.9 +/- 2.2 in patients with migraine and -19.1 +/- 5.4 nmol x dL(-1) x min(-1) in controls; p = 0.03). CONCLUSIONS: Patients with migraine are characterized by a distinct vascular smooth muscle cell dysfunction, revealed by impaired cyclic guanosine monophosphate and hemodynamic response to nitric oxide.

Association of pelvic endometriosis with alopecia universalis, autoimmune thyroiditis and multiple sclerosis.

An adult Caucasian female developed a previously unreported association of pelvic endometriosis (PE) with the triad of alopecia universalis (AU), autoimmune thyroiditis (AT) and multiple sclerosis (MS). Molecular human leukocyte antigen (HLA)-tissue typing of this subject showed the presence of the DR(2) 15 and DR(3) 17 alleles, which are associated to an increased risk of MS and AT, respectively. Clinical onset of AT followed withdrawal of corticosteroid treatment for AU, whereas MS become clinically evident after withdrawal from long-term estroprogestin therapy for PE. This clinical case is presented to discuss the autoimmune origin of PE, its possible association with multiple autoimmune disorders as well as the effect of other factors, such as administration and/ or discontinuation of specific hormonal regimens, on genetic autoimmunity-prone background.

A double-blind placebo-controlled trial of indobufen in the prophylaxis of migraine.

In a double-blind randomized trial of 42 patients with classic or common migraine, indobufen, an antiplatelet drug that inhibits platelet cyclo-oxygenase, was compared with placebo in the prevention of migraine. The duration of treatment was 3 months, and the efficacy was assessed on the basis of the following variables: frequency and duration of attacks, headache index (intensity x frequency); 35 completed the investigation. Indobufen at an oral dose of 200 mg b.i.d. reduced all the variables considered, where placebo did not. The drug was generally well tolerated. The findings of the preliminary trial suggest that indobufen might be an useful alternative in the prophylaxis of migraine.

The thymus and myasthenia gravis: immunological and neurophysiological aspects.

Myasthenia gravis (MG) is an autoimmune disorder, in which end-plate membrane damage is induced by antibodies directed toward various epitopes of the main immunogenic region of the nicotinic acetylcholine receptor (AChR). This article reviews the mechanisms responsible for the development of MG. Recent investigations into the roles of the thymus, antibodies against AChR, cytokines, and neuromuscular transmission have given new insight into the pathogenesis of MG. These new advances have led to a better understanding of the immune mechanisms in MG and have opened new therapeutic horizons.

Epilepsia partialis continua as a first symptom of multiple sclerosis: electrophysiological study of one case.

RATIONALE: The prevalence of epilepsy in people with multiple sclerosis (MS) is higher than in the general population. Sometimes seizures are among the first symptoms and can be unusual in their semiology. In rare cases a long-lasting focal somatomotor status [i.e., epilepsia partialis continua (EPC)] has been reported. CASE REPORT: A 21-year-old male patient presented with a clinical picture of EPC as a first symptom of MS at age of 19. A neurophysiological study agreed with a cortical origin of myoclonic jerks. CONCLUSIONS: MS should be considered a rare but possible aetiology of EPC in adults.

Mood disorders in epilepsy.

Depression is a common psychiatric problem associated with epilepsy. Interictal depressive symptoms are more frequent and severe in epileptic patients than in subjects with comparable chronic neurologic diseases or physical handicaps. Epileptic depression was characterized as major or dysthymic: bipolar depression is rarely described. Several Authors are of opinion that interictal depression is more frequent in epileptics with temporal lobe foci and, in particular, with temporal left hemisphere lesions. The pathogenetic significance of depression in epileptics is unclear. Some suggest the hypothesis that depression represents behavioral effects of neurochemical responses to brain injury for asymmetrical hemispheric distribution of neural substrate for mood. We think that depression in epileptic patients does not represent a psychological reaction to a particular cognitive or physical impairment, but it is in some way related to the type of epilepsy. In addition, some antiepileptic drugs may have psychotropic effects: the most positive findings were associated with carbamazepine.