Abnormal processing of the nociceptive input in Parkinson's disease: a study with CO2 laser evoked potentials

Since a number of patients with Parkinson’s Disease (PD) complain of painful sensations, we studied whether the central processing of nociceptive inputs is abnormal in PD. To test this hypothesis, we recorded scalp CO₂ laser evoked potentials (LEPs) to hand skin stimulation in 18 pain-free PD patients with unilateral bradykinetic-rigid syndrome (hemiparkinson) during the off state and in 18 healthy subjects. This technique allows us to explore non-invasively the functional status of some cerebral structures involved in nociceptive input processing. In both PD patients and control subjects, CO₂ laser stimulation gave rise to a main negative N2 potential followed by a positive P2 response at vertex peaking at a latency of about 200 and 300 ms, respectively. These potentials are thought to originate from several brain structures devoted to nociceptive input processing, including the cingulate gyrus and insula. PD patients and normal subjects showed comparable N2 and P2 latencies, whereas the N2/P2 peak-to-peak amplitude was significantly lower in PD patients (regardless of the clinically affected body side) than in controls. LEPs were even recorded after acute L-dopa administration in 7 additional PD patients. L-dopa administration yielded no significant change in N2/P2 amplitude as compared to the off state. These results suggest an abnormal nociceptive input processing in pain-free PD patients which appears to be independent of clinical expression of parkinsonian motor signs and is not affected by dopaminergic stimulation.     

Is interferon alpha in cutaneous T-cell lymphoma a treatment of choice?

This study was designed to evaluate the therapeutic efficacy and toxicity of recombinant interferon alpha-2a (rIFN alfa-2a) given as initial systemic therapy in untreated mycosis fungoides and/or Sezary's syndrome patients, at a slowly escalating schedule up to the maximal tolerated dose. At the same time this schedule was administered in patients who had relapsed or were refractory to previous treatment; 28 newly diagnosed and 15 previously treated patients entered the study. IFN was given daily with dose escalation from 3 to 18 MU. The last follow-up in June 1990 indicates that 90% of previously untreated patients who obtained a complete remission remain in continuous complete remission after 18 to 40 months and that 75% of previously untreated patients who obtained partial remission remain in partial remission after 20–44 months. The event-free survival projected, calculated using the Kaplan and Meier product limit technique, was 21% of all patients at 54·7 months (40% in the previously untreated groups and 14% in the previously treated group: P =0·12).
In conclusion, interferon is very effective as a single agent in cutaneous T-cell lymphomas.     

Facial dystonia: clinical features, prognosis and pharmacology in 31 patients

The natural history and response to different treatments were assessed in 31 consecutive patients with blepharospasm (BS) and/or oromandibular dystonia (OMD). The mean age at onset was 52.4 years and there was a female preponderance of 2.5 to 1. Ocular symptoms preceded the onset of blepharospasm in more than 50% of the affected patients, whereas psychiatric and dental problems prior to the onset of focal dystonia were found in 10% and 13% of the cases respectively. Dystonia elsewhere, mainly in the craniocervical area, was found in 23% of patients and appeared to follow a somatotopic progression. The first 2–3 years of history were crucial for the spread of dystonia to other face and body parts. When OMD was the first symptom, a lower tendency of dystonia to progress elsewhere was observed. A putative cause was found in 14% of patients who showed clinical and radiographic evidence of basal ganglia or rostral brainstemdiencephalon lesions. The response to different drugs was inconsistent although transient improvement was induced by haloperidol in 6 patients, by L-Dopa plus deprenyl in 3 patients, by trihexyphenidyl in 2 patients and by clonazepam in 2 patients. One, apparently spontaneous, remission was observed. Botulinum A toxin was iniected in the orbicularis oculi of 8 patients affected by BS: moderate to marked improvement lasting 5 to 30 weeks (mean 14.5 weeks) was achieved in all cases; transient ptosis, lasting 1 to 3 weeks, occurred in 3 cases.

---

Sommario La storia naturale e la prognosi della distonia faciale sono state valutate in una serie di 31 consecutivi pazienti con blefarospasmo (BS) e/o distonia oromandibolare (OMD) (età di esordio: 19–75 anni; durata di malattia: 1–15 anni; rapporto maschi/femmine: 2.5/1). Sintomi oculari precedevano l'insorgenza del BS in oltre il 50% dei pazienti, mentre anomalie dentali e problematiche psichiatriche comparivano come prodromi nel 10% e nel 13% dei casi rispettivamente. La sintomatologia distonica diffondeva, con andamento somatotopico, oltre il distretto cranio faciale nel 23% dei casi. Evidenze cliniche o radiologiche di lesioni dei gangli della base, della parte rostrale del tronco dell'encefalo o del diencefalo erano presenti solo nel 13% dei casi. Un lieve ma transitorio miglioramento della sintomatologia distonica era indotto da aloperidolo in 6 pazienti, da 1-dopa+deprenyl in 3, da triesifenidile in 2 e da lonazepam in 2. Solo 1 paziente andava incontro a remissione apparentemente spontanea della sintomatologia distonica dopo un anno di malattia. L'iniezione di tossina botulinica di tipo A negli orbicolari delle palpebre di 8 pazienti con BS induceva un sensibile miglioramento della sintomatologia distonica che persisteva per 5–30 settimane (media 14.5 settimane) con ridotti effetti collaterali locali (transitoria ptosi in 3 casi).

     

Planning genetic studies on primary adult-onset dystonia: sample size estimates based on examination of first-degree relatives

Primary adult-onset dystonia is thought to be partly genetic, but families large enough for a genome wide search are difficult to find. We examined the first-degree relatives of 76 primary adult-onset dystonia patients to assess the feasibility of model-free nonparametric methods that allow either screening of candidate loci (case-control design, transmission disequilibrium test [TDT], and sibling-TDT [S-TDT]) or identification of novel genes (affected sib-pair [ASP] method). Among the examined relatives, 1/34 parents, 13/149 siblings and 10/125 offspring were affected by adult-onset dystonia. The predicted sample sizes to detect a gene conferring an Odds ratio of 3.0 were 99 for case-control and TDT methodology, 148 for S-TDT, and 107 to 173 for an ASP study assuming three major loci. Based on our family structure, TDT, S-TDT, and ASP methods would required screening of about 220, 700, and 580 to 939 probands respectively. Analysing subpopulations with different types of dystonia, TDT required fewer probands with cervical/hand dystonia, S-TDT needed fewer probands with cranial dystonia. These sample size estimates suggest that the S-TDT may be feasible, whereas collection of cases for both TDT and ASP approaches would represent a major collaborative challenge.     

Chronic coffee consumption and striatal DAT-SPECT findings in Parkinson’s disease

Coffee may interfere with the dopaminergic transmission, and this action would possibly enhance motor activity and exert an antidyskinetic effect in Parkinson’s disease (PD). This study aimed to see whether coffee habit could be associated with change in striatal dopamine active transporter (DAT)-single photon emission computed tomography (SPECT) imaging in PD. A total of 83 PD patients (71 current coffee drinkers and 12 never drinkers) underwent a DAT-SPECT study, using [123I]FP-CIT as radionuclide. Socio-demographic and clinical information as well as smoking habit was collected at the time of imaging acquisition. The Unified Parkinson’s Disease Rating Scale part III was used to evaluate disease severity. On multivariable analysis, chronic coffee consumption was not associated with any significant change in striatal uptake of the radionuclide. However, the number of years patients drunk coffee was correlated with a significant increase in age at PD onset (p?<?0.001). Confirming a previous report, current cigarette smoking was associated with a reduction of radionuclide uptake in putamen and caudate (p?<?0.001).     

Speech-induced blepharospasm

Primary blepharospasm is an adult-onset dystonia typically present at rest and exacerbated by bright light, stress and voluntary movements of eyes and eyelids. Inconsistency or inducibility by activities involving muscles other than orbicularis oculi muscles are considered incongruous with typical primary blepharospasm, heralding the suspicion of psychogenicity. We report the clinical vignette of two patients manifesting an unusual presentation of primary blepharospasm, specifically triggered by voiced speech and associated with an otherwise ‘typical’ presentation of primary adult-onset dystonia in the lower face, larynx or upper limb. Speech-induced primary blepharospasm seems a rare occurrence, representing 1.3% of our clinic-based series of 149 patients with primary adult-onset primary blepharospasm. In these atypical patients, the feature of speech inducibility suggests that the abnormal surrounding inhibition between cortical subregions representing laryngeal and orbicularis oculi muscles might underlie dystonic overflow to the orbicularis oculi muscles following the voiced speech.     

The phenomenology of the geste antagoniste in primary blepharospasm and cervical dystonia

The geste antagoniste (GA), a relatively common feature of adult‐onset primary dystonia, has been systematically evaluated only in cervical dystonia, but it is still unclear whether its frequency and phenomenology differ among the various forms of focal dystonia. We analysed the frequency, phenomenology, effectiveness, and relationship of the GA with demographic/clinical features of dystonia in a representative clinical series of patients with the two most common forms of adult‐onset primary dystonia, blepharospasm (BSP) and cervical dystonia (CD). Clinical data were gathered using a standardized questionnaire, which showed substantial test‐retest reliability (κ = 0.79, P < 0.00001). The frequency of GA was similar among patients with BSP (42/59, 71.2%) and patients with CD (27/32, 84.4%), and in both groups GA showed similar effectiveness in reducing dystonia. The repertoire of GA was heterogenous in both BSP and CD patients, in whom seven BSP‐related and five CD‐related types of GA were recorded, and a “forcible” type of GA was present in 69% of BSP patients and in 48.1% of CD patients. In our whole patient population, age at dystonia onset was significantly lower among patients reporting a GA compared to those without GA (P = 0.01). GA features shared by BSP and CD predominate over differences, suggesting common mechanisms underlying this phenomenon in the two forms of primary adult‐onset dystonia. © 2010 Movement Disorder Society