Inclusion body myopathy associated with motor neuron syndrome: three case reports.

BACKGROUND: Hereditary inclusion body myopathy (h-IBM) is an autosomal-recessive or autosomal-dominant hereditary disease characterized by peculiar findings in muscle biopsies which resemble those occurring in inclusion body myositis (IBM). The absence of an inflammatory infiltrate in myofibers in h-IBM is a relevant differential criterion between the two pathologies. Motor neuron diseases (MND) represent a group of disorders involving both upper and lower motor neurons, characterized by fasciculations, progressive muscle weakness, and muscle atrophy. The most common form and prototype of MND is the amyotrophic lateral sclerosis (ALS) or Charcot's Disease, a progressive and fatal neurodegenerative disorder occurring in late adulthood. The pathogenesis of ALS remains still unknown, a variety of hypotheses having been proposed to account for the disease. The association of both pathologies is not common and offers new hypotheses about the pathogenic mechanisms in skeletal muscle and nervous system degeneration. PATIENTS AND METHODS: Described are three case reports in which we observed the clinical, laboratory and histopathological association of IBM and MND. In one case, dementia was also present. Muscle data was obtained by muscle biopsies and immunohistochemistry, while diagnosis of MND was supported by common neurophysiological techniques. RESULTS: The accumulation ofphosphorylated neurofilaments with a hereditary IBM-like pattern in skeletal muscle fibers without accumulation of amyloid-beta protein was observed. CONCLUSIONS: A better knowledge of the mechanisms in cellular death cascade could explain the pathogenesis of these different degenerative disorders.

SSRIs do not worsen Parkinson's disease: evidence from an open-label, prospective study.

Selective serotonin reuptake inhibitors (SSRIs) have been reported to be useful in the treatment of depression in patients with Parkinson's disease (PD). However, a few reports have suggested that SSRIs may worsen parkinsonian motor symptomatology and extrapyramidal side effects have been reported in depressed patients treated with SSRIs. So far, no prospective trial comparing the effects of different SSRIs in depressed patients with PD has been performed. The aim of the present study was to assess the effects of four SSRIs (citalopram, fluoxetine, fluvoxamine, and sertraline) on motor performance and their efficacy on depression in a group of patients with PD. Sixty-two consecutive nondemented, nonfluctuating, depressed patients with PD were included in four treatment groups (15 patiens received citalopram, 16 fluoxetine, 16 fluvoxamine, and 15 sertraline). The evaluation of extrapyramidal and depressive symptomatology was performed with use of the Unified Parkinson's Disease Rating Scale (UPDRS), Beck Depression Inventory, and Hamilton Depression Rating Scale at baseline and after 1, 3, and 6 months. Fifty-two patients completed the study. UPDRS scores were not significantly modified by the add-on therapy with each of the SSRIs studied. A significant improvement in depressive symptoms from baseline to the end of the trial was obtained with all SSRIs (Beck and Hamilton scores improving; p < 0.05 according to an analysis of variance). Our findings suggest that SSRIs do not significantly worsen extrapyramidal symptomatology and may ameliorate depression in patients with PD.

Thyroid function and autoimmunity in Parkinson's disease: a study of 101 patients.

Thyroid disease is the endocrine dysfunction most frequently reported in association with idiopathic Parkinson's disease (PD). The aim of this study was to assess thyroid autoimmunity and function in PD, and to verify the effect of long term l-dopa and/or dopamine therapy on thyroid function. We studied 101 consecutive PD outpatients and seventy age- and sex-matched neurological non-PD patients as controls. They were evaluated for free thyroid hormones, TSH and thyroid autoantibodies. No significant difference in the prevalence of thyroid autoimmunity and dysfunction was found between PD patients and neurological controls (10.8% in PD patients vs 10% in neurological controls). Further, treatment with l-dopa and/or dopaminergic drugs and the stage of Parkinson's disease did not affect thyroid function. In conclusion, the prevalence of thyroid autoimmunity in PD patients appeared similar to that as described in the general population, though thyroid dysfunction was observed in over than 10% of PD patients. Indeed, neurologists should be alerted to the possible complications arising from thyroid dysfunction in Parkinson's disease, but thyroid function tests should be performed only when justified on clinical grounds.

Clozapine in Parkinson's disease tremor. Effects of acute and chronic administration.

The effects of the acute administration of clozapine on parkinsonian mixed tremor (i.e., resting and postural tremors) were evaluated to establish clozapine's predictive value for long-term response and to determine if there is a difference in the pharmacologic responses of the two tremors. We also investigated the correlation between reduction of tremor and induction of sedation after acute and chronic administration of clozapine. Clozapine (12.5 mg) or placebo were administered po in a double-blind manner to 17 PD patients with mixed L-dopa-resistant tremors. Two patients did not reach 50% improvement and were considered nonresponders. The remaining 15 patients reported moderate to marked reduction of tremor. Responsive patients in the acute test moved on to a long-term, open clozapine add-on study receiving an average daily dose +/- SD of 45 +/- 9.6 mg for a period of 15.5 +/- 8.3 months. A significant reduction of both resting (p < 0.05) and postural (p < 0.05) tremors was observed under clozapine from the first week of treatment through the entire period of the study. There was no statistically significantly difference between the degree of improvement for resting and postural tremors after either single or chronic clozapine administration. Sedation was the only side effect reported after clozapine; however, the time courses of sedation and tremor reduction did not coincide in the acute or in the chronic experimental paradigm, where it decreased considerably in a few weeks in all patients. During long-term clozapine treatment, neither systemic side effects nor worsening of motor disability scores were noted. Thus we wish to propose an acute test or a therapeutic attempt, or both, with clozapine before defining a case of mixed parkinsonian tremor as resistant tremor and therefore resorting to a neurosurgical approach.

Dihydroergocryptine in the treatment of Parkinson's disease.

In the last 20 years dopamine agonists have been considered more and more helpful as primary therapy for Parkinson's disease (PD). Recently the neuroprotective activity and the therapeutic efficacy of a new ergot derivative, alpha-dihydroergocryptine (DHEC), has been highlighted. In the present work we resume the experimental and clinical data reported about this drug. The rationale for dopamine (DA) agonists as primary therapy for Parkinson's disease (PD) is based on the possibility to delay the onset of long term I-dopa syndrome (LTS) (King, 1992); moreover DA agonists seem to exert a neuroprotective effect on substantia nigra neurons. In fact, they stimulate DA receptors bypassing the degenerating nigrostriatal neurons and their metabolic machinery (Lieberman, 1992; Olanow, 1992); more recently, some studies have shown that these drugs have a direct protective effect too (Felten et al., 1992; Yoshikawa et al., 1994). In this minireview we resume the data reported about neuroprotective activity and therapeutic efficacy of a new ergot derivative, alpha-dihydroergocryptine (DHEC).