Cytokine Production by Mononuclear Cells from Patients with Familial Infantile Bilateral Striatal Necrosis.

Prompted by findings suggesting immune instability in infantile bilateral striatal necrosis (IBSN), we evaluated levels of proinflammatory (tumor necrosis factor α, interleukin [IL]-1ß, IL-6, interferon [IFN]γ) and anti-inflammatory (IL-10 and IL-1ra) cytokines produced by peripheral blood mononuclear cells (PBMC) from 6 children with IBSN and 11 age-matched controls. Compared to controls, non-stimulated PBMC from the IBSN group produced a significantly lower level of IL-1ra (by 38%; p < 0.001) and significantly lower levels of TNFα, IL-1ß, and IFNγ (by 36% [p < 0.001], 25% [p = 0.06], and 32% [p < 0.02]) under PBMC stimulation. The severe cachexia manifesting shortly after IBSN onset may impair the immunological state, placing patients at risk of death from hyperpyrexia and sepsis.

Bilateral striatal necrosis caused by ADAR mutations in two siblings with dystonia and freckles-like skin changes that should be differentiated from Leigh syndrome.

Pathogenic molecular variants in the ADAR gene are a known cause of rare diseases, autosomal recessive Aicardi- Goutières syndrome type 6, severe infantile encephalopathy with intracranial calcifications and dominant dyschromatosis symmetrica hereditaria, demonstrated mainly in Asian adults. Recently, they have been also found in patients with nonsyndromic bilateral striatal necrosis accompanied by skin changes of the freckles-like type. Here, we present Polish siblings with acute onset and slowly progressive extrapyramidal syndrome with preserved intellectual abilities and basal ganglia changes found in MRI. A Leigh syndrome was considered for a long time as the most frequent cause of such lesions in children. Finally, two molecular variants in non-mitochondria-related ADAR gene c.3202+1G>A (p.?) and c.577C>G (p.Pro193Ala) were revealed by whole exome sequencing. We suggest that bilateral striatal necrosis should be always differentiated from LS to prevent the diagnosis delay. The striatal involvement accompanied by the presence of freckles-like skin changes should direct differential diagnosis to the ADAR gene mutations screening.

[Differential diagnosis of Parkinson's syndromes--an overview]. / Differenzialdiagnostische Massnahmen bei Parkinsonsyndromen--eine Ubersicht.

With regard to aging of the general population non-neurologists are more frequently confronted with patients presenting with parkinsonian symptoms. The central task concerning treatment and prognosis in such cases is to differentiate idiopathic Parkinson's disease from secondary Parkinson syndromes and so called Parkinson-Plus-Syndromes. Besides clinical presentation neuroimaging techniques have been established in recent years, which can help with correct classification in early disease stages and difficult cases. In this article, we review the current clinical pathways for differential classification of parkinsonian symptoms with a special emphasis on clinical assessment and neuroimaging techniques like NMR and transcranial sonography.

Progression of putaminal degeneration in multiple system atrophy: a serial diffusion MR study.

By using diffusion-weighted imaging (DWI), we have recently shown abnormal diffusivity in the putamen of patients with the Parkinson variant of multiple system atrophy (MSA-P) which also correlated with disease severity, indicating the capability of putaminal diffusivity to serve as a marker for disease progression. We therefore performed a serial DWI study in 10 patients with MSA-P compared to 10 patients with Parkinson's disease (PD) to evaluate the dynamic evolution of diffusion properties in the basal ganglia including putamen, caudate nucleus and globus pallidum by means of the trace of the diffusion tensor (Trace(D)). For comparison, we have also analyzed the frequency and semiquantitative grading of MSA-P-related structural changes on conventional MRI including putaminal atrophy, lateral hyperintense margination of the putamen and putaminal signal hypointensity relative to the globus pallidum on T2 MR images. None of the Trace(D) values in the basal ganglia regions in the PD group changed significantly at follow-up compared to baseline. In MSA-P, a significant increase of the Trace(D) was found in the putamen, which correlated with motor progression as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS). No significant change of any of the abnormal putaminal findings on routine MRI was obtained. We suggest that abnormal diffusivity in the putamen is sensitive to change over time in MSA-P and correlates with motor progression indicating that DWI may serve to monitor disease progression in MSA-P in an objective and quantitative manner.

Neuroimagen en los trastornos del movimiento / Neuroimaging in movement disorders

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Aplicación del FP-CIT-I-123 en la práctica clínica de pacientes con parkinsonismo / Application of 123I-FE-CIT in the clinical practice in Parkinsonism patients

Introducción: La SPECT con FP-CIT-I-123 ha sido avalada en los últimos años por numerosos estudios como una técnica muy valiosa para evaluar la integridad presináptica de la vía estriato nígrica. El presente estudio tiene como objetivo realizar un análisis descriptivo de los principales aspectos diagnósticos extraídos de los 110 primeros estudios realizados con FP-CIT en nuestro centro. Material y métodos: Se incluyeron a 110 pacientes reclutados de forma consecutiva, distribuidos en 5 grupos según el diagnóstico clínico de presunción, con un período de seguimiento de al menos un año. La exploración gammagráfica se valoró tanto cualitativa como cuantitativamente. Resultados: El 61,8 % (68/110) de los estudios fueron considerados como patológicos y el 38,2 % (42/110) no presentaron alteraciones. Entre lo estudios patológicos hubo una concordancia con el diagnóstico clínico del 88,3 % (60/68). En el grupo de exploraciones consideradas normales, la concordancia fue del 83,4 % (35/42). En los pacientes con Enfermedad de Parkinson (EP), se apreció correlación inversa estadísticamente significativa entre captación estriatal y severidad según grado H&Y (r = ­0,4) y entre valoración cualitativa y cuantitativa (r = ­0,86). No se obtuvo significación entre pérdida fisiológica de función dopaminérgica y edad, ni entre grado de asimetría a nivel estriatal en los distintos grupos. Conclusiones: Se observó en general una adecuada concordancia entre diagnóstico clínico y resultado de la SPECT con FP-CIT. En los pacientes con EP se obtuvo correlación inversa entre captación estriatal y grado de H&Y y mayor grado de asimetría a nivel estriatal que en el resto de grupos

Introduction: 123I-FP-CIT scan has been supported in the last years by numerous studies as a technique of undeniable value to assess presynaptic integrity of the nigrostriatal pathway. The objective of this study is to perform a descriptive analysis of the main diagnostic aspects obtained from the first 110 studies made with FP-CIT in our center. Material and methods: The study population consisted of 110 consecutive patients distributed into 5 groups according to the clinical diagnosis, after a follow-up period of at least one year. Qualitative and quantitative scintigraphy was done. Results: A total of 61.8 % (68/110) of the studies were considered abnormal and 38.2 % (42/110) as normal. Among the abnormal examinations there was 88.3 % (60/68) agreement with the clinical diagnosis and agreement was 83.4 % (35/42) in the normal examinations. Inverse significant correlation was assessed between striatal binding and severity according to the H&Y scale (r = ­0.4) and between qualitative and quantitative assessment (r = ­0.86). There was no significant correlation between the degeneration of dopaminergic function according to age and degree of asymmetry on striatal binding in the different groups. Conclusions: Generally an adequate agreement between clinical diagnosis and SPECT-FP-CIT was observed. Inverse correlation between striatal binding and H&Y scale and greater asymmetry at striatal binding was obtained among Parkinson patients than in the rest of groups

Contribución de la SPECT cerebral de trazadores de dopamina en el diagnóstico de la atrofia multisistémica / Contribution of dopamine transporters brain SPECT to multisystemic atrophy diagnosis

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Stimulation of growth-hormone release with clonidine does not distinguish individual cases of idiopathic Parkinson's disease from those with striatonigral degeneration.

Multiple System Atrophy (MSA) and idiopathic Parkinson's disease (PD) can be difficult to distinguish. There is an ongoing debate about the diagnostic value of the growth-hormone response to clonidine (CGH-test) in PD and MSA. We investigated whether the CGH-test can identify individual patients in the early stages of PD (n = 21) and Striatonigral Degeneration (SND, n = 11), a particular variety of MSA. Patients were diagnosed on the basis of clinical criteria and IBZM-SPECT. Clonidine induced a greater total serum growth-hormone production in PD than in SND (p = 0.01). However, taking the difference in prevalence of PD and SND into account, and because of the low likelihood ratios of the test, an increase of GH after clonidine increases the pre-test probability for PD by about only 5 %, while an absent response of GH also increases the pre-test probability for SND by about 5 %. We conclude that the CGH-test discriminates between groups of patients with PD and SND, but has little practical diagnostic value for identifying individual patients.

Thin section MR study of the basal ganglia in the differential diagnosis between striatonigral degeneration and Parkinson disease.

PURPOSE: Signal abnormalities within the putamen in MRI have been related to tissue degeneration in the striatonigral variant of multiple system atrophy (MSA-P). While previous work demonstrated the high specificity of these MR findings, sensitivity rates were unsatisfactory. We evaluated the specificity and sensitivity of an acquisition protocol using thin section MRI to differentiate MSA-P from Parkinson disease (PD). METHOD: Axial 3-mm-thick conventional T2 and proton density spin echo images at the level of basal ganglia were acquired at 1.5 T in 24 patients with MSA-P and 27 patients with PD. RESULTS: We found an abnormal putaminal T2 hypointensity in 21 of 24 MSA-P patients (87.5% sensitivity) and a proton density hyperintensity in 20 of 24 MSA-P patients (83.3% sensitivity). Three among 27 PD patients had an abnormal putaminal T2 hypointensity (88.8% specificity) and there were no proton density abnormalities (100% specificity). CONCLUSION: Our thin section conventional spin echo protocol showed a substantial increase in MR sensitivity compared with previous reports. We believe that a better depiction of even mild signs of degeneration in the putamen may allow a more widespread use of this technique in the differential diagnosis of parkinsonisms.

Postural and action myoclonus in patients with parkinsonian type multiple system atrophy.

Patients with a parkinsonian syndrome and features of multisystem atrophy (pMSA) may exhibit abnormal movements of the hands and fingers, which are reported in the literature either as "jerky" tremor or myoclonus. We studied clinically and electrophysiologically these movements in 11 consecutive patients with pMSA. No abnormal movements were observed when the patients were at complete rest, except for a characteristic parkinsonian "pill-rolling" tremor in one patient. Abnormal small-amplitude, nonrhythmic movements involving just one or a few fingers, or more rarely the whole hand, were observed in nine patients when holding a posture or at the beginning of an action. Accelerometric recordings showed small-amplitude irregular oscillations which, contrary to those of patients with tremor, had no predominant peak in the Fast Fourier frequency spectrum analysis. Electromyographic recordings in the forearm and hand muscles showed brief jerks of less than 100 ms duration which were synchronous in antagonist muscles of the forearm and alternated with brief periods of silence. Electrical stimulation of the digital nerves evoked consistent reflex responses in the wrist flexor and extensor muscles at a latency of 55.3+/-4.1 ms (range, 50-63 ms). Routine electroencephalographic (EEG) and somatosensory evoked potentials to median nerve stimulation were normal. Back-averaging of the EEG activity time-locked to the jerks was performed in two patients with no evidence of abnormal cortical activity. Two patients had episodes of transient respiratory failure related to pneumonia. This caused a long-lasting enhancement of the abnormal hand and finger movements, which became larger and more widespread, with features of posthypoxic myoclonus. We conclude that the abnormal hand and finger movements of patients with pMSA are a form of postural and action myoclonus, and can be described as mini-polymyoclonus.