Julia Vaamonde

“Pulsatile” administration of levodopa has been invocated a relevant factor for motor fluctuations in Parkinson's disease (PD). We studied dopaminergic sensitivity to apomorphine in 10 parkinsonian patients with motor fluctuations. Patients were tested as follows: the minimal effective dose of apomorphine (MED‐1) was administered in the morning to induce anonresponse. Fifteen minutes after this motor response had disappeared, an apomorphine infusion was initiated and maintained to ensureonperiods of three different durations on different days. Infusion lasted for ∼30, 60 and 90 minutes. Subsequently, the infusion was stopped, and after 15 minutes in theoffstate, a second bolus of apomorphine (MED‐2) was given. The mean infusion doses were 49.2 ± 5.4, 108.4 ± 10.3, and 150 ± 8.2 mg. These elicitedonperiods of 48.2 ± 4.1, 110 ± 4.5, and 195 ± 3.8 minutes. The MED‐2 elicitedonresponses with a duration of 30 ± 4.5, 18.4 ± 3.2, and 11.2 ± 4.1 minutes. The duration of theonresponse induced by the apomorphine infusions correlated inversely (P< 0.01) with theoninduced by the MED‐2 of apomorphine. Our findings indicate that a continuous dopaminergic stimulus may induce pharmacodynamic changes associated with tolerance in PD patients. © 2009 Movement Disorder Society

In 1929, Critchley introduced the term “vascular parkinsonim” (VP), which has been the subject of considerable controversy in neurology. Parkinsonism does not appear to be a frequent consequence of striatal infarcts, although unilateral parkinsonim has been reported as an acute or subacute onset syndrome following strategic infarcts in the striatum. Previous 123-I ioflupano SPECT (DaTSCAN) studies involving radioisotope labeling of the dopamine transporter protein at presynaptic level in patients with IPD (idiopathic Parkinson’s disease) have found this technique to be highly sensitive in exploring the nigrostriatal pathway. Previous studies of VP with DatSCAN have been inconclusive. The present study correlates clinical data (unilateral parkinsonim following contralateral lenticular infarction), and radiological (CT/MRI) and functional neuroimagin findings (DatSCAN) in 5 patients with CT/MRI criteria for striatal infarcts. Finally, in 2 of these patients a diagnosis of IPD was made because of the follow-up of clinical signs and pathological DaTSCAN findings not concordant with the size and location of the vascular lesion.

Primary orthostatic tremor (OT) is defined as a clinical syndrome with high frequency (13-18 Hz) tremor when standing predominantly involving legs and trunk. OT is thought to be driven by an unique supraspinal tremor generator. Previous studies suggest that the nigrostriatal dopaminergic transmission is impaired in patients with OT. All three patients at an age of 56, 45 and 72 years fulfilled the diagnosis criteria of primary OT. The duration of illness amounted to 4, 3 and 1 year, respectively. The three patients had single-photon emission computed tomography (SPECT) using 123-I-FP-CIT as dopamine transporter tracer (DatSCAN). DatSCAN was normal in every patient. OT is considered to be caused by a central oscillator because high-frequency tremor bursts are time locked in arm, leg, trunk, and even facial muscles and peripheral stimulation does not reset the tremor. Some reports suggest that the central generator may be located in the posterior fossa. In our patients presynaptic nigrostriatal pathway was normal.

Dementia with Lewy bodies (DLB) is one of the main differential diagnosis of Alzheimer's disease (AD). In DLB there is 40-70% loss of striatal dopamine and the loss of dopaminergic cell is accompanied by loss of the dopamine transporter. The loss of dopaminergic neurons in DLB can be confirmed in vivo with I-FP-CIT (DaT-SCAN), a pre-synaptic dopamine transporter marker. There are no changes in DaT-scan in AD compared with controls. AIM. The use of DaT-SCAN for the differential diagnosis between AD and DLB. We use the DaT-SCAN to study the nigrostriatal pathway in 6 patients with dementia and moderate parkinsonism. The Mini-Mental Test and the Unified Parkinson's Disease Rating Scale, motor part only (UPDRS), were performed. A SPECT scan was carried out 3 to 4 hours after administration of 185 MBq FP-CIT (ioflupane) a dopaminergic presynaptic ligand. With occipital cortex used as a radioactivity uptake reference, ratios for the caudate nucleus and the anterior and posterior putamen of both hemispheres were calculated. All scans were also rated by a simple visual method. All patients had dementia with moderate fluctuations in cognitive function, parkinsonian syndrome and hallucinations. DaT-SCAN was normal in 2 patients and pathological in 4. The sensitivity and specificity of the DLB criteria vary markedly. FP-CIT SPECT may be a new tool in the differential diagnosis between DLB and AD.

Essential tremor (ET) may be misdiagnosed as idiopathic Parkinson's disease (PD). In neurodegenerative diseases, structural imaging, such as CT or MRI, is of limited value for differentiating parkinsonian syndromes since structural changes are often only evident by the time the disease is far advanced. Most cases of symptomatic parkinsonism are vascular parkinsonism, but PD may coexist. The differential diagnosis between Alzheimer's disease (AD) and dementia with Lewy bodies (LBD) is often difficult. To define the utility of functional neuroimaging test to establish differential diagnosis between PD and ET, drug induced parkinsonism, multiple system atrophy and vascular parkinsonism, and between AD and LBD, when clinical presentation, evolution or treatment response are atypical. A group of 75 patients with parkinsonism was examined by clinical assessment and DaTSCAN (123I-FP-CTI, dopamine transporter protein marker) and/or IBZM SPECT (D2 receptor marker). The patients were recruited from our outpatient clinic. Correlation between initial clinical diagnosis and functional imaging studies (DaTSCAN and/or IBZM SPECT) in our patients did not reach that described (more than 90 %) for these techniques in previously published studies. Conclusions. According to sensitivity and sensibility reported in previous imaging studies of the pre and/or postsynaptic dopaminergic system using DaTSCAN and/ or IBZM, SPECT may be a new tool in the diagnosis of parkinsonian patients with difficult clinical diagnosis.

Orthostatic tremor (OT) is clinically defined as a tremor of the lower limbs and trunk on walking. It bears a significant functional impairement. Although the term orthostatic tremor was first used by Heilman in 1984, Pazzaglia et al had previously described some cases in 1970. Despite the fact that the pathophysiology of this entity is not fully known, the presence of a central oscillator is generally accepted as being responsible. A high frecuency tremor, between 13 and 18 Hz, constitutes an almost patognomonic finding, and treatment with clonazepam usually improves the symptoms. We present a patient who described his symptoms as "cramps" in lower limbs and trunk on standing up, which were relieved on walking or resting. This clinical presentation together with a neurophysiological recording of the tremor showing an activity of lower frequency (8 Hz) combined with the usual higher frequency (16 Hz) and above all the clear amelioration of symptoms when treated with gabapentin, i.e. resolution of the low frequency tremor without changes in the 16 Hz tremor, were the peculiar features of this case which merits discussion. The slow component of the orthostatic tremor is crucial in this case. The improvement with gabapentin is explained by the disappearance of this slow c

The differential diagnosis of a parkinsonian syndrome is extensive and complex. In most cases, however, a detailed clinical examination will help to differentiate between idiopathic Parkinson's disease (IPD) and other causes of parkinsonism. 10 patients with an average age of 65.1 years (range 60-70), of whom 6 were men and 4 women were referred to our department with a diagnosis of IPD and history of backwards falls. The average duration of disease was 4.7 years (range 4-7). All 10 patients had at presentation a severe akinetic-rigid syndrome with no other symptoms of IPD. I.v. apomorphine (APO) was administered to each of them at a rate of 8.9 mg/hr (range 15.3 mg/hr) for an average time of 5.4 hours (range: 3-10 hours). The improvement of the akinetic-rigid state in six of the patients during the i.v. infusion with APO helped to elicit signs that are atypical of IPD (ataxia and postural instability). Three of the patients did not respond to i.v. APO and one of them could not be evaluated, as he did not tolerate the infusion. Oral Dopa challenge or s/c APO bolus has not been as successful in helping to differentiate IPD from other parkinsonian syndromes. The prompt detection of postural instability or retropopulsion is necessary in order to diagnose atypical parkinsonian syndromes. In difficult cases, continuous i.v. APO will improve the akinetic-rigid state and facilitate the detection of atypical signs. The pharmacokinetic characteristics of APO, and the advantage of it being possible to administer the drug i.v. in a few hours increases the viability of this test.

[corrected] Entacapone was given to try to improve the motor complications in eight patients with Parkinson's disease (PD) treated chronically with levodopa, with daily severe motor fluctuations and dyskinesias. We introduced entacapone (200 mg added to every dose of levodopa) to 8 parkinsonian patients (mean age: 68.25 +/- 2.3; range: 68-72; mean PD duration: 10.4 +/- 2.7 years) treated with oral levodopa, plus a dopa-decarboxylase inhibitor (mean dose: 706.25 +/- 2.3 mg/day; mean period of levodopa-treatment; 9 +/- 2.3 years). Dyskinesias were present in all patients (chorea: 8 patients; "off"--dystonia: 4; byphasic dyskinesias: 3). The type and duration (time "on" and "off") of fluctuations was categorized on the "on-off" charts drawn up by the patients or their relatives, and observation by the investigators after the introduction of entacapone. One patient, with severe impairment with entacapone, was evaluated (motor response) during i.v. apomorphine infusion (40 mg, during 3 hours). The combination of levodopa and entacapone was associated with a net increase in "off" time in all patients (from 5.8 +/- 1.2 h to 12.4 +/- 4.4 h) without change in the URPD. In the patient studied with i.v. apomorphine, "off" periods appeared during the infusion. These findings suggest that increased daily levodopa consumption may reduce striatal responsiveness to dopaminergic stimulation in severe parkinsonian patients. These data should be considered when planning the treatment strategy of complex parkinsonian patients.