Paolo Solla

Gender differences in motor and non-motor symptoms among Sardinian patients with Parkinson's disease

BACKGROUND Parkinsons disease (PD) occurs more frequently in men than in women and a higher risk for PD development in males compared with females has been hypothesized, suggesting gender may be a significant factor in the development and progression of parkinsonism. To date, gender differences in non-motor symptoms are under-reported. OBJECTIVE To assess gender differences in motor and non-motor symptoms among Sardinian PD patients. METHODS One hundred fifty-six (91 male and 65 female) consecutive Sardinian PD outpatients were included in this analysis. Modified Hoehn and Yahr scale and UPDRS were used to assess motor symptoms, while non-motor disturbances were evaluated with the non-motor symptoms scale (NMSS). Presence of depression, anxiety and other iatrogenic behavioral disorders was also investigated. In order to determine how gender differences could be specific to PD, 132 age-matched normal controls were assessed with the NMSS. RESULTS Women were more likely than men to present with tremor as initial symptom (p<.025) and worse UPDRS instability score (p<.02). NMSS score in females was significantly higher than that in males (p<.018). A significantly higher severity in cardiovascular (p<0.002), sleep/fatigue (p<.018) and mood/apathy (p<.001) domains was observed in female PD patients, while the sexual dysfunction domain was reported with a significantly higher score in male patients (p<.017). Fatigue (p<.03), lack of motivation (p<.015) and sadness (p<.009) were observed significantly more frequent in females, while altered interest in sex was noted as more common in males (p<.001). Frequency of depression (p<.011) and anxiety (p<.001) was significantly higher in females, while male patients had increased frequency of compulsive sexual behaviors (p<.05). There was a significantly higher frequency of non-motor symptoms in eight domains in both male and female PD patients compared with controls (p<.001, for all comparisons, with the exception of urinary disturbances in females: p<.004). Only sexual dysfunctions were not significantly higher in male and female PD patients compared with controls. DISCUSSION The present study highlights the role of gender differences associated with the occurrence of motor and non-motor disorders and our findings indicate that spectrum and severity of non-motor symptoms may present with different gender distribution in PD patients, suggesting a possible sex-related effect.

Reversible Pisa syndrome in patients with Parkinson’s disease on dopaminergic therapy

BackgroundThe wide variability of dystonic postures manifested in the clinical course of Parkinson’s disease (PD) represents a complicated on-going issue. Several recently published reports of Pisa syndrome (PS) in parkinsonian patients on dopaminergic therapy have described a variable means of onset and clinical course of this truncal dystonia.ObjectiveTo describe PD patients with PS, with the aim of stressing the frequent iatrogenic origin and potential reversibility of this syndrome during the initial stages of its appearance.Subjects and methodsEight consecutive PD patients who developed a PS after modifications of antiparkinson therapy were studied. All patients underwent detailed clinical assessment, [123I]FP-CIT-SPECT being performed in three cases. Four patients were videotaped.ResultsAll patients developed PS within a variable time-span ranging from 15 days to 3 months after adjustment of treatment. Seven cases of PS were manifested following an increase and one a decrease of dopaminergic treatment. A marked reversal of dystonia was produced in the first seven patients by the withdrawal or dose decrease of dopaminergic PS priming drug, and in the eighth patient an increase of dopaminergic therapy was necessary.ConclusionsIn our opinion, the recognition of reversibility of PS during the initial stages of its appearance may be of considerable clinical importance. Indeed, it may facilitate the rapid withdrawal or reintroduction of dopaminergic treatment, thus avoiding an initial veering towards the subchronic variant and, subsequently into a chronic irreversible variant.

Hypersexual behaviour, frotteurism and delusional jealousy in a young parkinsonian patient during dopaminergic therapy with pergolide: A rare case of iatrogenic paraphilia

Neuropsychological and psychopathological modifications induced by dopaminergic drugs in patients with Parkinsons disease (PD) are invariably not taken into sufficient consideration by the neurologist. Among the former, modifications of sexual urges and behaviours are of particular importance with regard to severity and variety of clinical pictures. Although rare, such modifications may assume the connotations of an aberrant sexual behaviour with criminal implications, in line with a diagnosis of paraphilia. The authors report the case of a 51-year-old male PD patient who, after a few years of dopaminergic treatment with pergolide, developed a paraphilic disorder, consistent with DSM-IV TR diagnosis of frotteurism, and delusional jealousy. The patient presented mild motor impairment and lack of or negligible cognitive deterioration, thus providing evidence that these disorders are not typical of advanced PD. Pergolide was reduced and quetiapine, an atypical neuroleptic, was introduced with subsequent subsiding of the paraphilic disorder and improvement of delusional jealousy.

Behavioral, neuropsychiatric and cognitive disorders in Parkinson's disease patients with and without motor complications.

BACKGROUND Parkinsons disease (PD), commonly defined as a hypokinetic movement disorder, is hampered by the appearance of motor complications (MC), including dyskinesias and motor fluctuations, and non-motor symptoms such as behavioral, neuropsychiatric and cognitive disorders, which, in the last years, are gaining increasing attention. The factors affecting MC and these non-motor symptoms are still largely unknown and their interactions are not yet fully evaluated. OBJECTIVE To identify the presence of behavioral, neuropsychiatric and cognitive disorders in PD patients with and without MC and to evaluate their association with MC. METHODS Consecutive PD patients received a comprehensive structured clinical evaluation including pharmacologic treatment, MC and non-motor symptoms such as reward-seeking behaviors, neuropsychiatric symptoms (depression, anxiety, psychoses and hallucinations) and dementia. RESULTS 349 patients were included in this analysis. Patient with MC showed enhanced frequency of dementia (p < 0.001), anxiety, depression and psychoses (p < 0.01). A higher frequency of impulse control disorders was detected in patients with dyskinesias (22.2% - p < 0.001) and motor complications (12.2% - p < 0.05). Dyskinesias were significantly more present in patients with hypersexuality (p < 0.05) and compulsive shopping (p < 0.001), while they were not significantly associated with pathological gambling and binge eating. Patients with dyskinesias also had significantly higher frequency of dopamine dysregulation syndrome, hallucinations and delusions (p < 0.001), with the exception of delusional jealousy. DISCUSSION We found a higher frequency of behavioral, neuropsychiatric and cognitive disorders in patients with MC. The lack of detection of dyskinesias in several PD patients with pathological gambling in our study represents a very interesting issue. While binge eating mainly seems to be related to the use of dopamine agonists, the significant lack of association between dyskinesias and delusional jealousy suggests the hypothesis of a possible underlying psychopathological predisposition rather than a mere pharmacologic effect in PD patients with these behavioral complications.

Othello syndrome in Parkinson disease patients without dementia.

Background:Delusional jealousy or Othello syndrome (OS) is a well-described psychiatric disorder with paranoid features reported in both organic and functional psychoses. In organic psychoses, the disorder occurs more frequently among chronic male alcoholics and in demented patients. To date, only 2 anecdotal cases of OS have been reported in Parkinson disease (PD) during dopaminergic treatment. Objective:To investigate the presence of OS in PD patients and to study the relationship between dopaminergic treatment, avoiding the possible influence of dementia. Methods:Five hundred sixty-three PD patients without dementia encountered in our movement disorders practice were included in the study. All patients who developed OS were studied. Relationships between clinical and familial history and dopaminergic therapy and OS were assessed. Results:Six patients with OS were identified. They were all male, with a relatively recent diagnosis of PD characterized by mild-moderate motor deficit. Dopaminergic treatment had been prescribed at low dosages. Neither confusional states (including agitated confusion) nor delirium were associated with OS. The disorder became manifest mainly at time of introduction/increment of antiparkinson treatment. Invariably, OS decreased or receded after reduction/suspension of the antiparkinson drug and prescription of an atypical neuroleptic, usually clozapine or quetiapine. Conclusion:We hypothesize that nondemented PD patients affected by OS do not necessarily present with severe motor complications and may well have a biologic predisposition for psychiatric disorders. In our opinion this paranoid delusion is rarely considered in PD.

Heat shock protein 27 R127W mutation: Evidence of a continuum between axonal Charcot-Marie-Tooth and distal hereditary motor neuropathy

Background Heat shock protein 27 (HSP27) mutations have been reported to cause both Charcot-Marie-Tooth disease (CMT) type 2F and distal hereditary motor neuropathy (dHMN) although never previously in a single family. Objective To analyse clinical and electrophysiological findings obtained in a single large Sardinian family bearing the HSP27 R127W mutation. Methods Twenty-one members of a five generation Sardinian family have been studied, including thirteen members affected by peroneal muscular atrophy and proved heterozygous for the known HSP27 R127W mutation. Twelve patients and eight unaffected relatives were subjected to clinical examination. A standardised electrophysiological study was performed in eleven patients and six unaffected relatives. Results Mean age at onset (±SD) was 31.2±7.2 years. Mean age at investigation was 45.2±12.9 years and mean disease duration at the time of investigation was 14±12.9 years. According to current criteria for CMT2 and dHMN, of the 10 patients who had undergone both clinical and neurophysiological examination, five were diagnosed as CMT2, two as dHMN and a further two patients were labelled as an intermediate type. Finally, due to the presence of spastic paraplegia, the index patient did not meet established criteria for the diagnosis of CMT or dHMN. Discussion Findings obtained in the present study, broadening the spectrum of clinical manifestations of disorders associated with HSP27 mutations, support the hypothesis of a continuum between CMT2 and dHMN forms and suggest a possible common spectrum between these entities and several forms of CMT plus pyramidal features (HMSN V), providing important implications for molecular genetic testing.

Finasteride attenuates pathological gambling in patients with Parkinson disease.

To the Editors: Dopamine replacement therapies (DRTs) are dependable tools to attenuate the motor impairments and bradyphrenia of patients with Parkinson disease (PD); in predisposed individuals, however, these agents can trigger impulse-control disorders (ICDs) such as pathological gambling (PG), hypersexuality, and compulsive shopping. The pharmacological armamentarium for the psychiatric sequelae of DRTs is limited and unsatisfactory; the main therapeutic strategy, based on dosage reduction or DRT switching, is not always successful and can compromise the clinical course of PD. This background highlights the urgent need for novel therapies for iatrogenic ICDs in patients with PD. We recently discovered that inhibition of steroid 5>reductase (S5>R), the key enzyme in the synthesis of androgens and neurosteroids, elicits antidopaminergic, but not extrapyramidal, effects in animals. The prototypical S5>R inhibitor, finasteride (FIN), is clinically approved for the treatment of benign prostatic hyperplasia and male-pattern alopecia, is generally well tolerated, and induces few adverse effects. We found that this drug elicited therapeutic effects in patients affected by disorders related to dopaminergic dysregulation, such as Tourette syndrome. Here, we report that FIN induced a remarkable improvement of DRTinduced PG in 2 male patients with PD. In all patients, the severity of the motor impairment was evaluated as IIIYIV in the Hoehn-Yahr rating scale, and the Unified PD Rating Scale III score was between 20 (4) and 45 (7) during the on and off periods, respectively. Pathological gambling was diagnosed based on the DSM-IV Text Revision criteria, and symptoms were monitored using the Italian version of the Yale-Brown Obsessive-Compulsive Scale modified for PG.

Imaging of the dopamine transporter predicts pattern of disease progression and response to levodopa in patients with schizophrenia and parkinsonism: a 2-year follow-up multicenter study

Similarly to subjects with degenerative parkinsonism, (123)I-FP-CIT SPECT has been reported either normal or abnormal in patients with drug-induced parkinsonism (DIP), challenging the notion that parkinsonism might be entirely due to post-synaptic D2-receptors blockade by antipsychotic drugs. In a previous multicenter cross-sectional study conducted on a large sample of patients with schizophrenia, we identified 97 patients who developed parkinsonism with a similar bi-modal distribution of DAT-SPECT. In this longitudinal study, we reported clinical and imaging features associated with progression of motor disability over 2-year follow-up in 60 out of those 97 patients with schizophrenia and parkinsonism who underwent (123)I-FP-CIT SPECT at baseline evaluation (normal SPECT=33; abnormal SPECT=27). As second end-point, chronic response to levodopa over a 3-month period was tested in a subgroup of subjects. Motor Unified Parkinsons Disease Rating Scale (UPDRS) at follow-up significantly increased in patients with abnormal SPECT. Specifically, a 6-point worsening was demonstrated in 18.5% of the subjects with abnormal SPECT and in none of the subjects with normal SPECT. Levodopa treatment improved motor UPDRS only in the group with abnormal SPECT. After adjustment for possible confounders, linear regression analysis demonstrated that abnormal SPECT findings at baseline were the only predictor of motor disability progression and of better outcome of levodopa treatment. Our results support the notion that a degenerative disease might underlie parkinsonism in a minority of schizophrenic patients chronically exposed to antipsychotics. Functional imaging of the dopamine transporter can be helpful to select this patient sub-group that might benefit from levodopa therapy.

Aberrant sexual behaviours in Parkinson’s disease during dopaminergic treatment

Sirs: Although modifications in sexual behaviour are a well-known occurrence during dopaminergic therapy in Parkinson’s disease (PD) [2], they can also assume connotations of serious psychiatric disorders such as paraphilias and other aberrant sexual behaviours, to date scarcely reported in the literature. These aberrant sexual behaviours (ASB) can include criminal, antisocial or immoral actions such as rape, paedophilia, incest, zoophilia, frotteurism, exhibitionism, etc. Less dramatically, aberrant but not criminal behaviours such as excessive masturbation, buying, collecting pornographic material or voyeurism, can be observed. We report on nine consecutive patients with PD, according to clinical criteria [7], observed during an 11-year period that developed ASB whilst undergoing dopaminergic treatment. Invariably the presence of ASB was spontaneously reported by the spouse or other relatives, referring to dramatic events including rape, incest, paedophilia, zoophilia, frotteurism, exhibitionism, obsessive masturbation, obsessive buying, collecting and viewing of pornographic material, voyeurism and hyperlibidinous behaviour. Records were prepared for all patients with regard to clinical features, dopaminergic treatment at ASB onset, Hoehn and Yahr staging [6], Unified Parkinson’s Disease Rating Scale (UPDRS) motor scale [3], Global Deterioration Scales (GDS) [13], Mini Mental State Examination (MMSE) [5], neuroimaging (MRI or CT), pre-existence of drug-induced minor psychiatric disorders and motor complications associated with levodopa therapy. The characteristics of the patients are summarised in Table 1. Eight patients presented with signs of motor complications associated with levodopa therapy, and in all of these patients the ASB took place in the ‘‘on’’ period. The occurrence of ASB was mainly manifested following the introduction or increment of a dopamine agonist (more frequently pergolide) and only in one case with levodopa alone. During the period of our observations, pergolide was actually the most commonly prescribed dopamineagonist in our clinical practice, although ergot and non-ergot derivatives were prescribed equally. In the first 7 patients (behaviour with criminal connotations) the drug in question was immediately reduced or suspended and clozapine introduced (with the exception of patient 7 where quetiapine was added instead of clozapine). In patients 8 and 9 (aberrant, but not criminal behaviour), as a first step a reduction/withdrawal of the dopamine agonist was attempted: this proved satisfactory in patient 9, with disappearance of ASB, but was not sufficient in patient 8, thus rendering necessary the subsequent addition of clozapine. In no case was dopaminergic treatment totally suspended. Over an 11-year period of observation, the manifestation of ASB in nine PD patients during dopaminergic therapy, while the literature presents only rare anecdotal reports [1, 2, 4, 8, 10, 14], suggests that the phenomenon is likely to be largely underestimated. Although these types of behaviour are often punishable by law and may at times lead to imprisonment, in our case series, the occurrence of ASB mainly took place in a family setting and no types of legal proceedings were undertaken by relatives, with the exception of one patient. Previous studies reported that sexual disorders, such as hypersexuality, are increasingly observed in advanced PD [11] or in parkinsonian patients treated with highdoses of dopaminergic drugs [9, 10]. On the contrary, our observations seem to illustrate a wide sphere of conditions in which ASB may be manifested. Indeed, only two of our patients (patients 1 and 8) were at an advanced stage of PD. The core of our study was represented by six patients (patients 2–6 and 9): all presented with initial motor complications associated with levodopa therapy, although none had a clinical history of psychiatric or sexual conduct disorders, with the A. Cannas Æ P. Solla Æ G.L. Floris G. Serra Æ P. Tacconi Æ M.G. Marrosu Centro per i Disordini del Movimento Dipartimento di Scienze Cardiovascolari e Neurologiche Sezione Neurologia University of Cagliari Cagliari, Italy

Effects of an adapted physical activity program on motor and non-motor functions and quality of life in patients with Parkinson's disease

BACKGROUND Several studies have clearly shown that strategies of health promotion, such as fitness and general exercise programs, may improve quality of life (QoL), motor and non-motor functions in Parkinsons disease (PD) patients. However, little is known about the effects of specific Adapted Physical Activity (APA) programs on PD patients. OBJECTIVE To determine the effects of an APA program on motor and non-motor symptoms, functional performances and QoL in PD patients. METHODS Nine consecutive PD patients (5 men, 4 women, 64.4 ± 6.8 years) able to ambulate independently (Hoehn and Yahr: from stage 1 to 3) and not demented, were enrolled. Patients performed an APA program, 3 sessions/week, for 9 weeks. Exercises focused on balance, walking, strength and functional activities. Functional effects were assessed by Six Minute Walking Test (6MWT), Five Time Sit to Stand Test (FTSST), Berg Balance Scale (BBS), Sit and Reach Test (SRT), and Timed Up and Go test (TUG). Motor impairment and disability were assessed using the Unified Parkinsons Disease Rating Scale - part III (UPDRS-III) and the Hoehn and Yahr Scale, respectively. Non-motor symptoms were evaluated by PD Fatigue Scale (PFS), Beck Depression Inventory II (BDI-II) and PD Quality of life scale, 8 items (PDQ-8). RESULTS A significant decrease in resting HR (67.55 ± 10.85 vs 70.22 ± 12.34 bpm, p < 0.05) and a significant increase in walked distance (p < 0.0005) were observed. A significant impairment of the muscles strength was noted (FTSST, p < 0.05). BBS showed a significant increase in balance abilities (p < 0.0005) and safety with mobility (TUG, p < 0.005) was enhanced. Finally, a significant improvement in motor and non-motor symptoms was detected: UPDRS-III (p < 0.00005), PFS (p < 0.005), BDI-II (p < 0.05) and PDQ-8 (p < 0.05). CONCLUSIONS A tailored exercise program in PD patients could be effective as an adjunct to conventional therapy on improving daily activities, motor and non-motor symptoms, with better QoL.