Use of Rasch analysis to refine a patient-reported questionnaire on satisfaction with communication of the multiple sclerosis diagnosis.

BACKGROUND: The Comunicazione medico-paziente nella Sclerosi Multipla - Revised (COSM-R) is a patient self-assessed questionnaire probing the moment of multiple sclerosis (MS) diagnosis disclosure (section 1, five items) and following period (section 2, 15 items). OBJECTIVES: This study examined COSM-R dimensionality and measurement properties through Rasch analysis (partial-credit model) and proposed a revised questionnaire. METHODS: Cross-sectional COSM-R data were obtained from 1068 people with MS (PwMS, 1065 questionnaires) participating in four studies (102 centres). Mean age was 40 years (range 17-73); 70% were women; 53% were from Northern, 25% from Central, and 21% from Southern Italy. RESULTS: Unidimensionality was not confirmed for COSM-R section 1, but was for section 2 after removal of three items. The revised instrument (COSM-S, Shortened) consisted of the original five-item checklist (section 1), modified by removing the table grouping of three items, and 12 of the original 15 section 2 items, which could now be summed and transformed into an interval scale. Scores were higher for items assessing emotional satisfaction than for those assessing informational satisfaction. CONCLUSIONS: The proposed COSM-S is a composite measure of satisfaction with MS diagnosis communication with improved metric properties over the original COSM-R, and whose section 2 satisfies Rasch model expectations.

Observational case-control study of the prevalence of chronic cerebrospinal venous insufficiency in multiple sclerosis: results from the CoSMo study.

BACKGROUND: Chronic cerebrospinal venous insufficiency (CCSVI) has been proposed as a possible cause of multiple sclerosis (MS). OBJECTIVES: The CoSMo study evaluated the association between CCSVI and MS. METHODS: The primary end-point of this multicentric, case-control study was to compare the prevalence of CCSVI between patients with MS, patients with other neurodegenerative diseases (ONDs) and healthy controls (HCs). Color-coded duplex sonography was performed by a sonologist and the images were sent to one of three central sonologists for a second reading. Agreement between local and central sonologists or, in case of disagreement, the predominant judgment among the three central readers, was required for a diagnosis of CCSVI. All readings, data collection and analysis were blinded. RESULTS: The study involved 35 MS centers across Italy and included 1874 subjects aged 18-55. 1767 (94%) were evaluable: 1165 MS patients, 226 patients with ONDs and 376 HCs. CCSVI prevalence was 3.26%, 3.10% and 2.13% for the MS, OND and HC groups, respectively. No significant difference in CCSVI prevalence was found amongst the three cohorts (MS versus HC, OR = 1.55, 95%CI = 0.72-3.36, p = 0.30; OND versus HC, OR = 1.47, 95%CI = 0.53-4.11, p = 0.46; MS versus OND, OR = 1.05, 95%CI = 0.47-2.39, p = 0.99). High negative and low positive agreement was found between the local and centralized readers. CONCLUSIONS: CCSVI is not associated with MS.

A new grading for easy and concise description of functional status after spinal cord lesions.

BACKGROUND: Disability scales do not enable the transmission of concise, meaningful and daily function description for clinical purposes. STUDY DESIGN: Cross-sectional statistical analysis of 328 patients' Spinal Cord Independence Measure (SCIM) III item scores (SIS). OBJECTIVE: To develop a concise and clinically interpretable data-based characterization of daily task accomplishment for patients with spinal cord lesions (SCLs). SETTING: Multi-center study at 13 spinal units in 6 countries. METHODS: Patients were grouped into clusters characterized by smaller differences between the patients' SIS within the clusters than between their centers, using the k-medoides algorithm. The number of clusters (k) was chosen according to the percent of SIS variation they explained and the clinical distinction between them. RESULTS: Analysis showed that k=8 SIS clusters offer a good description of the patient population. The eight functional clusters were designated as A-H, each cluster (grade) representing a combination of task accomplishments. Higher grades were usually (but not always) associated with patients implementing more difficult tasks. Throughout rehabilitation, the patients' functional grade improved and the distribution of patients with similar functional grades within the total SCIM III score deciles remained stable. CONCLUSIONS: A new classification based on SIS clusters enables a concise description of overall functioning and task accomplishment distribution in patients with SCL. A software tool is used to identify the patients' functional grade. Findings support the stability and utility of the grades for characterizing the patients' functional status.

Identification of malignant plasma cell precursors in the bone marrow of multiple myeloma.

Precursors of plasma cells were studied in the bone marrow of 28 patients with multiple myeloma, plasma cell leukemia, and benign monoclonal gammopathy. Pre-B and B cell populations were analyzed with anti-B monoclonal antibodies corresponding to the clusters standardized at the Leucocyte Typing Workshops in Paris and Boston (CD9, CD10, CD19-22, CD24). In advanced forms of plasma cell malignancies, such as cases of multiple myeloma in stages II and III and of plasma cell leukemia, some cells of lymphoid morphology expressed common acute lymphoblastic leukemia antigen (CALLA, CD10) and HLA-DR, but contained no detectable terminal deoxynucleotidyl transferase enzyme. These CALLA+ cells were absent in benign monoclonal gammopathies. In multiple myeloma, the CALLA+ cells were negative for surface and cytoplasmic immunoglobulins (Ig), and, unlike CALLA+, terminal deoxynucleotidyl transferase (TdT+) pre-B cells in the normal bone marrow also failed to react with antibodies to B cell-associated antigens such as CD9, CD19, CD22, and CD24. The CALLA+, Ig- cells could be regarded as preplasmacytic since, after having been separated and stimulated with the phorbol ester 12-0-tetradecanoyl-phorbol-13 acetate in vitro, they transformed into plasma cells and synthesized the same heavy and light chains as myeloma cells.

Functional assessment in rehabilitative medicine: principles and methods.

In rehabilitative medicine, functional assessment means a decision process that results from the interaction between classifications (for example, diagnostic) and measures, and that aims to recognize, anticipate or modify the interaction between the disabled person and his environment. In this context, the measure is the intersection of a person along the conceptual gradient and continuum ''from less to more'' attributed to variability in the ''total person,'' such as independence, pain, cognitive capacity, or fatigability. The principal instrument is the additive questionnaire (functional scale). This consists of various items believed to represent a common variable. These kinds of variables are observable only partially across various aspects of the whole person, and are not completely predictable. Their measure, consequently, can only be derived from an estimated statistic. The additive questionnaire is the principal measurement instrument. Several items all representing the same variable receive scores whose sum is assumed to be proportional to the quantity of the underlying variable. For various reasons the sum of the scores does not represent a true linear and continuous measure like those seen in chemistry and physics. Recently developed methods, in particular Rasch analysis, can extract true measures from raw scores. Thanks to better measurement of variability in persons within rehabilitative medicine, functional assessment can become increasingly more valid and informative.

Rehabilitation and outcome measurement: where is Rasch analysis-going?

Outcomes are clinical or functional changes at the whole-person level. Measures are based on questionnaires which summate scores assigned to a series of items representing a person's variable. The metric properties of raw scores are known to be of limited validity. Yet, such variables represent the main target of outcome assessment in Rehabilitation Medicine as far as they may cover performances, perceptions and knowledge. Rasch statistical models, first available in English to a large readesrship in late 70s, allow to transform the arbitary raw scores into true linear measures. Rehabilitation seemed a privileged field for the application of Rasch models, yet these are still far from becoming popular. A bibliometric study was conducted across ten leading digital libraries. A MEDLINE search showed a dramatic increment of published papers covering the intersection between the MESH terms ''Rehabilitation'' and ''Outcome assessment'', which rose in from 5 to 4 302 between the 1981-90 and 2001-07 time frames, respectively. ''Rasch'' paper also rose remarkably from 35 to 539. When the triple intersection was considered, articles only rose from 0 to 12. Results point towards a privileged application of Rasch analysis to build and refine questionnaires, rather than to actually measuring people. Commentaries and suggestions are invited.

Crying spells triggered by thumb-index rubbing after thalamic stroke: a case report.

BACKGROUND: Pathologic crying, devoid of any emotional counterpart, is known to occur as a consequence of various brain stem, cortical hemispheric and cerebellar lesions or, quite exceptionally, of "dacrystic" epilepsy. The case reported here suggests that thalamic lesions may also cause crying spells, under the special circumstances described below. CASE PRESENTATION: After a mild left thalamic stroke a caucasian 77 years old man presented with crying spells with no emotional counterpart, triggered by thumb-index rubbing of his right hand. Only a modest sensation loss on right infra-orbital and nose-labial areas and the first three right fingers could be detected at clinical examination. The circumstances and processes leading to the crying spells were investigated, together with their neural substrate. Brain computerized tomography (CT), magnetic resonance imaging (MRI) and functional magnetic resonance imaging (fMRI) were conducted. Neurophysiologic studies included Video-Electroencephalography, Electromyography, motor and sensory Evoked potentials. Active thumb-index rubbing, passive fingertips stimulation and interaction of sensory-motor stimulation with cognitive/speech activities were tested under different paradigms. A treatment with pregabalin (75 mg twice a day) was attempted. CT and MRI showed a small ischemic infarct in the left ventral postero-lateral thalamus, while fMRI led to the expected findings, i.e. a bilateral activation of the hand motor representation during the crying-triggering right-hand finger rubbing activity. Sensory potentials evoked from stimulation of the right upper limb were the only abnormal neurophysiologic test. Crying spells could be invariably evoked by both real and imagined active finger rubbing, in either the left of right hemi-space. Rubbing by an examiner was ineffective. Immersion in water (18 °C) but not oiling of the fingertips prevented the symptom. Administration and discontinuation of pregabalin 75 mg daily could be associated with suppression and reappearance of the symptom, respectively. CONCLUSIONS: In this patient loss of sensation seemed to generate crying spells rather than the more common allodynia. As a matter of speculation, both symptoms might represent responses to a sensory loss, but in this case the pathway might have been selectively affected providing inhibition from the lateral to the medial segment of the VPLT, which is linked to the anterior cingulate (limbic) cortex engaged in emotional behaviour.

Depression is the main determinant of quality of life in multiple sclerosis: a classification-regression (CART) study.

PURPOSE: Quality of life in multiple sclerosis has been often measured through the SF-36 questionnaire. In this study, validation of the SF-36 summary scores, its 'physical' component, and its 'mental' component was attempted by exploring the joint predictive power of disability (EDSS score), of anxiety and depression (HADS-A and -D scores, respectively), and of disease duration, progression type, age, gender and marital status. METHOD: The sample consisted of 75 patients suffering from multiple sclerosis admitted to an inpatient rehabilitation unit. The interplay between potential predictors was assessed through a particular regression model (classification and regression tree, CART). Two main advantages of this technique are its robustness with respect to distributional assumptions (rarely met by scores coming in from questionnaires) and its sensitivity to high-order interactions, between independent variables, difficult to detect through conventional multiple regression. RESULTS: Predictive variables for physical component of the SF-36 were EDSS and HADS-D (36.8% variance explanation). The only predictive variable for mental component of SF-36 was HADS-D (39.1% variance explanation). CONCLUSION: Results confirm previous findings showing that in patients with multiple sclerosis quality of life is heavily determined by person's mood, whatever his/her neurological or functional severity. The usefulness and validity of the SF-36 as an index representative of quality of life is debatable, as long as depression explains much of its variance. Further refinement of quality of life definition and measurement is worth further psychometric and statistical research.

[A group therapy assessment tool (GrETha-Q)]. / Uno strumento per la valutazione dell'attività terapeutica di gruppo (GrEThA-Q).

This paper presents a questionnaire designed to assess the aspecific treatment efficacy and subjective perceived efficacy of group therapy. A preliminary version of the instrument was administered to a sample of 151 subjects undergoing group therapy. The psychometric properties of the instrument were evaluated by means of the Rasch model, and showed a good score range, good reproducibility and adequate coherence. The hierarchy of difficulty of the items remained stable among the respective categories of sex, age and professional level.

C3b receptors mediate the growth factor-induced proliferation of malignant B-chronic lymphocytic leukemia lymphocytes.

We have investigated the function of C3b receptor (CR1) in the malignant lymphocytes of B-chronic lymphocytic leukemia (B-CLL) mimicking the physiological ligand C3b with the anti-CR1 monoclonal antibody CB04 covalently linked to Sepharose CL-4B (CB04-S). The binding of insolubilized CB04-S to CR1 gave a progression signal to B-CLL cells which became B cell growth factor (BCGF)-responsive. The cells of 13 of 14 cases treated with CB04-S showed an active time-dependent proliferation when BCGF was added to the culture. After 72 hr of exposure to BCGF, the growth fraction evaluated with the Ki67 monoclonal antibody was 23.4 +/- 8.9 and the proportion of cells in S phase assessed by the bromodeoxyuridine incorporation technique was 18.6 +/- 8.5%. The proper sequence of CB04-S followed by BCGF was also important since the proliferation was halved when the sequence was reversed or the two signals were delivered concomitantly. CB04-S and BCGF alone failed to induce any significant proliferation; the percentage of cycling cells was less than 1% overlapping that of control culture cells. On the contrary, the proliferation of normal tonsil B cells was triggered both by CB04-S and by BCGF used as single agents (bromodeoxyuridine+ cells 12.7 +/- 5.1% and 20.0 +/- 7.3, respectively). Together these data indicate that malignant B-CLL cells need a sequential two-step signal based upon CR1 binding in order to be activated in vitro. This is a major difference with normal tonsil B lymphocytes whose proliferation is triggered both by CB04-S and by BCGF used as single agents.

The ABILHAND questionnaire as a measure of manual ability in chronic stroke patients: Rasch-based validation and relationship to upper limb impairment.

BACKGROUND AND PURPOSE: Chronic hemiparetic patients often retain the ability to manage activities requiring both hands, either through the use of the affected arm or compensation with the unaffected limb. A measure of this overall ability was developed by adapting and validating the ABILHAND questionnaire through the Rasch measurement model. ABILHAND measures the patient's perceived difficulty in performing everyday manual activities. METHODS: One hundred three chronic (>6 months) stroke outpatients (62% men; mean age, 63 years) were assessed (74 in Belgium, 29 in Italy). They lived at home and walked independently and were screened for the absence of major cognitive deficits (dementia, aphasia, hemineglect). The patients were administered the ABILHAND questionnaire, the Brunnström upper limb motricity test, the box-and-block manual dexterity test, the Semmes-Weinstein tactile sensation test, and the Geriatric Depression Scale. The brain lesion type and site were recorded. ABILHAND results were analyzed with the use of Winsteps Rasch software. RESULTS: The Rasch refinement of ABILHAND led to a change from the original unimanual and bimanual 56-item, 4-level scale to a bimanual 23-item, 3-level scale. The resulting ability scale had sufficient sensitivity to be clinically useful. Rasch reliability was 0.90, and the item-difficulty hierarchy was stable across demographic and clinical subgroups. Grip strength, motricity, dexterity, and depression were significantly correlated with the ABILHAND measures. CONCLUSIONS: The ABILHAND questionnaire results in a valid person-centered measure of manual ability in everyday activities. The stability of the item-difficulty hierarchy across different patient classes further supports the clinical application of the scale.

Phenotypic, cytogenetic and molecular characterization of a new B-chronic lymphocytic leukaemia (B-CLL) cell line.

A lymphoid cell line was established from a patient with B-cell chronic lymphocytic leukaemia (B-CLL) by infecting blood lymphocytes with Epstein-Barr virus (EBV). Immunoglobulin gene rearrangement studies and the presence of a chromosome marker (isochromosome 17q) provided the formal proof that the line has originated from the neoplastic B cells. The morphology and phenotype indicate that the EBV-induced cell line has reached a plasma cell-like stage of differentiation.

Vasoactive hormones induce nitric oxide synthase mRNA expression and nitric oxide production in human endothelial cells and monocytes.

Isoform-2 nitric oxide synthase (NOS-2) mRNA expression and nitric oxide (NO) production are induced in endothelial cells and monocytes by cytokines such as gammaIFN and LPS. We evaluated NOS-2 and isoform-3 NOS (NOS-3) mRNA expression and NO production in human monocytes and human umbilical vein endothelial cells (HUVEC), under basal conditions and after incubation with physiologic concentrations of vasoactive hormones. NOS mRNA expression was detected by reverse transcription polymerase chain reaction (RT-PCR) and NO production by electronic paramagnetic resonance spectroscopy (EPR). We showed that NOS-2 mRNA expression and NO production were induced by stimulation with epinephrine, dopamine, endothelin-1, and angiotensin II, both in monocytes and HUVEC. NOS-3 mRNA expression and NO production were detected under basal conditions in monocytes and HUVEC and were not modified by the presence of vasoactive hormones. Human endothelial cells and monocytes express the NOS-2 and NOS-3 mRNA and the inducible NOS-2 mRNA expression increases after vasoactive hormone stimulation.

The use of outcome measures in physical medicine and rehabilitation within Europe.

The aim of the study was to survey the use of outcome measures in rehabilitation within Europe. It was envisaged that this would provide the basis for further studies on the cross-cultural validity of outcome measures. A postal questionnaire was distributed in November 1998 to 866 units providing rehabilitation. In total, 418 questionnaires were returned, corresponding to a response rate of 48%. These 418 centres treated an estimated 113,000 patients annually, undertaking 360,000 assessments. The survey focused on nine diagnostic groups: hip and knee replacement, low back pain, lower limb amputees, multiple sclerosis, neuromuscular disorders, rheumatoid arthritis, spinal cord lesions, stroke and traumatic brain injury. It identified a relatively small number of dominant outcome assessments for each diagnostic group and some variation in the preference for measures across regions. A large number of measures, however, are being used in one or a small number of locations and with relatively few patients. For rehabilitation of orthopaedic patients the majority of assessments undertaken are at the impairment level. For patients with neurological disorders the emphasis is mostly upon measures of disability.

Pathological gaits: inefficiency is not a rule.

Theenergy expenditure per unit distance, or cost of gait, depends on the efficiency of the locomotory mechanism, which is a function of speed. We compared the cost of gait at corresponding speeds between pathologic (hemiplegic, above-knee amputee, paraplegic) and normal subjects respectively, using a polynomial regression on data available from the literature. In all pathologies the cost-speed function showed a minimum at a speed which may be defined as optimum, as in normal gait. Within the speed range possible for the patients, the cost-speed functions were significantly different from the normal one in the above-knee amputee and in the paraplegic, but not in the hemiplegic. In the amputee, the minimum cost was increased by 38% with respect to that of the normal at a corresponding speed. In contrast, the minimum cost was increased by only 11 % in the paraplegic, despite the much more severe impairment.

The influence of age on length of stay, functional independence and discharge destination of rehabilitation inpatients in Italy.

Advanced age in itself does not predict a poor functional outcome or a longer length of stay in rehabilitation units. Seven hundred and sixty-four adult cases were analysed, from 14 post-acute rehabilitation facilities throughout Italy. Data came from the national database run by the agency distributing the Italian version of an internationally validated scale of disability, the FIM [symbol: see text] sm (Functional Independence Measure). The FIM is an 18-item scale rating independence in the domains of selfcare, sphincter control, mobility, locomotion, communication and social cognition. The total FIM score may range from 18 to 126 (higher score = greater independence). Patients were classified with respect to the cut-off age of 75 years (76+ and 75-, mean age 82 and 57 years, n = 203 and 561, 27% and 73% of the cases, respectively). The median interval between onset of disability and admission to the facility (onset-to-admission delay, OAD) was 36 and 45 days in the 76+ and the 75- group, respectively (p < 0.001). Mean admission FIM score was 70 (+/- 28) in the 76+ and 71 (+/- 27) in the 75- group. Discharge FIM scores were 84 +/- 29 and 93 +/- 26, respectively (p < 0.001). Median length of stay (LOS) was 34 days in the 76+ and 41 days in the 75- group, respectively (p < 0.005). The 76+ and 75- groups were discharged home in 86% and 90% of the cases, respectively (p = 0.053). The results suggest that inpatient rehabilitation is substantially effective and efficient for older as well as for younger patients.

[Assessment of a patient satisfaction scale in rehabilitation]. / Validazione di una scala di soddisfazione del paziente in degenza riabilitativa.

BACKGROUND: A new scale is presented, measuring patients' satisfaction with respect to the quality of care during stay in a rehabilitation unit. The questionnaire is self-administered and anonymous, and it includes 15 items, scored 1 to 4. The cumulative score may thus range 15-60; the higher the score, the higher the patient's satisfaction. MATERIALS AND METHODS: The instrument was proposed to 175 disabled patients, admitted to a free-standing Centre for rehabilitation following neurological or orthopedic impairments. RESULTS: One hundred and forty questionnaires were completed. Of these, 131 could be analyzed. The mean score was > 3 in every item. Factor analysis disclosed that the questionnaire comprises 5 factors, which may be defined as "medical care", "physiotherapy", "nursing care", "food" and "physical environment and facilities". A satisfactory internal consistency of the items was found (item-remainder correlations > 0.5, Cronbach alpha > 0.9). This suggests that the scale is sufficiently unidimensional to permit cumulative summing of the item scores. CONCLUSIONS: The results suggest the content and construct validity of the scale. The questionnaire thus merits further psychometric investigation.

[Validity and reliability of a new questionnaire on patient satisfaction in rehabilitative therapy]. / Validità ed affidabilità di un nuovo questionario sulla soddisfazione del paziente in degenza riabilitativa.

BACKGROUND: The aim of this study was to examine some psychometric properties of a new questionnaire measuring patients' satisfaction with respect to the quality of care during stay in a rehabilitation unit. The instrument (called SAT-16) is composed of 16 four-level items and 2 open-ended questions. The construct validity of the 16-item section was already demonstrated in a previous study based on factorial analysis. In this study the concurrent validity, further aspects of the construct validity and test-retest reliability were analyzed. METHODS: The SAT-16 was administered to 339 inpatients, admitted consecutively to a Rehabilitation Center. RESULTS: 262 questionnaires (77%) were returned, of which 221 with all items filled in. The SAT-16 correlated well with two other measures of satisfaction (CSQ-8 and global satisfaction regarding the hospital stay). The answers to two open-ended questions came out to be consistent with those to the 16 closed-ended questions. The high values for the indices of test-retest reliability (ICC and kappa) are evidence of the stability of the scores in two repeated administrations. CONCLUSIONS: The SAT-16 was found to be provided with good psychometric characteristics. It can be proposed as a valid instrument for use in clinical practice for the continuous quality improvement of inpatient medical rehabilitation programmes.

A short measure of balance in multiple sclerosis: validation through Rasch analysis.

Ambulatory patients with multiple sclerosis (MS) frequently present with poor balance. Neither static nor dynamic posturography explore balance during self-paced movements in real-life activities, when fall is most probable. Behavioural item-response scales can easily represent these activities. However, testing many items can easily cause fatigue in MS patients, thus distorting their scores. On the other hand, the lower the number of items, the lower the precision of the cumulative score and its reliability. A new short instrument was derived from existing ones (the Tinetti and the Berg balance scales). A preliminary 10-item version encompassed sit/stand manoeuvres, standing with eyes open and closed, standing with eyes closed and head extended, leaning forward while standing, picking up an object from floor, resisting nudges on the sternum, turning around, tandem stance. The instrument was administered 1-3 times to 55 MS patients (103 observations overall), all of them able to walk autonomously for at least 20 metres. The Rasch Analysis was adopted to explore the psychometric validity of the scale. Two items (Stand-to-sit and Standing with eyes open) were deleted, as they were too easy and thus uninformative. The remaining 8 items made up a scale (called EQUI-SCALE) complying with the requirements of unidimensionality and reliability. The item scores remained stable in a sub-sample of 24 patients tested before and after ten 1-hour exercise sessions, thus supporting the homogeneity of the items.

[Parkinson syndrome induced by veralipride]. / Sindrome parkinsoniana indotta da veralipride.

Veralipride, an antidopaminergic drug commonly prescribed to counteract postmenopausal symptoms, may cause reversible parkinsonism. A 49-year-old healthy woman reported a 5 month history of progressive slowing of voluntary movements, postural changes, e.g. sit-to-stand manouevres, and gait. Clinical examination revealed moderate hypokinesia, hypomimia and plastic rigidity of the four limbs. Locomotor oscillations of the upper limbs were decreased. She had been taking 100 mg of veralipride daily to counteract postmenopausal symptoms (vasomotor flushes and irritability) for 17 months uninterruptedly. The drug was withdrawn. The patient's clinical picture fully normalized within 20 days. One year later she reported to be still asymptomatic. This seems to be a case of parkinsonism induced by veralipride, a drug known to cause other extrapiramidal signs such as bucco-facial or limb dyskinesia. To our knowledge, only one other such case has been published (a 77-year-old French woman who had been taking veralipride, prazepam and nicergolin). In both cases, the drug had been administered for longer and without intervals. In our patient the motor disturbances could not have been associated with either advanced age or interaction with concurrent medications. Therefore, this case is suspected for veralipride-associated parkinsonism. In conclusion, intoxication should be thought in case of parkinsonism arising in women taking this drug.