Early hyperdopaminergic state following sub-thalamic nucleus deep brain stimulation in Parkinson disease.

BACKGROUND: Hyperdopaminergic state (HS), especially impulse control behaviors (ICBs), are not rare in Parkinson's disease (PD). Controversial data regarding HS prevalence one year following sub-thalamic nucleus deep brain stimulation (STN-DBS) are reported. OBJECTIVE: Our objectives were to describe early postoperative HS (PoOHS) including ICBs, hypomania and psychotic symptoms during the first 3 months following STN-DBS (V1) and their prognosis at 1 year (V2). METHODS: This descriptive study included 24 PD patients treated successively with bilateral STN-DBS between 2017 and 2019. The primary endpoint was prevalence of PoOHS at V1 according to the Ardouin Scale of Behaviour in Parkinson's Disease. RESULTS: Prior to STN-DBS (V0), 25% patients had HS (only ICBs) whereas at V1 (during the 3 first months), 10 patients (41.7%) had one or several HS (P=0.22) (de novo in 29.2%): 7 (29.2%) ICBs, 4 (16.7%) hypomanic mood, 1 (4.7%) psychotic symptoms. At V2, all V0 and V1 HS had disappeared, while 1 patient (4.2%) presented de novo HS (P<0.01). No correlation was found between the occurrence of PoOHS at V1 and any V0 data. Higher levodopa equivalent dose of dopamine agonists at V1 was correlated with ICB at V1 (P=0.04). CONCLUSION: We found that early PoOHS are frequent in PD after STN-DBS, mostly de novo, with ICBs and hypomania being the most frequent. Despite a good prognosis of PoOHS at one year, our work emphasizes the importance of both a cautious adjustment of dopamine agonist doses and a close non-motor monitoring pre- and post-STN-DBS in PD.

Clonidine GH stimulation test to differentiate MSA from idiopathic late onset cerebellar ataxia: a prospective, controlled study.

INTRODUCTION: Despite the consensus criteria for multiple system atrophy (MSA), the diagnosis of MSA of cerebellar type (MSA-C) may be difficult in the early stage of the disease. There are several differential diagnoses including idiopathic late-onset cerebellar ataxias (ILOCA) and it is often necessary to wait for clinical worsening so that the criteria can be met. Our aim was to assess the efficacy of clonidine growth hormone test (CGH test) to distinguish MSA-C from ILOCA in the early stage of the disease. METHODS: Within our cohort of late-onset sporadic, progressive cerebellar ataxia, the group of patients meeting the criteria for possible or probable MSA was compared to the ILOCA group. Clinical and paraclinical examination including CGH test were repeated during the prospective follow-up. RESULTS: Eighty-six patients were recruited, including 42 patients in the MSA group and 44 ILOCA patients with a mean follow-up of 33 months. At the inclusion visit, CHG test was pathological for 31% MSA of patients and 18.2% of ILOCA patients (p = 0.35). During the follow-up, 52.4% of MSA-C had a pathological CGH test, while only 20.5% of ILOCA (p < 0.01). CGH test had a sensitivity of 69.1% and a specificity of 68.2%, (p < 0.001) for MSA-C patients; CGH test allows in three quarters of cases, if negative, to rule out a probable MSA-C (negative predictive value of 75%, p = 0.0014). CONCLUSION: This prospective, controlled study showed that CGH test could be helpful in clinical practice to differentiate MSA-C from ILOCA in the early stage of the disease.

Brain MRI of multiple system atrophy of cerebellar type: a prospective study with implications for diagnosis criteria.

AIM: The second consensus statement for the diagnosis of multiple system atrophy type cerebellar (MSA-C) includes pons and middle cerebellar peduncle (MCP) atrophy as MRI features. However, other MRI abnormalities such as MCP hyperintensity, hot cross bun sign (HCB), putaminal hypointensity and hyperintense putaminal rim have been described. OBJECTIVES: To evaluate, in patients with sporadic late-onset cerebellar ataxia (SLOCA), the discriminative value of several MRI features for the diagnosis of MSA-C, to follow their evolution during the course of MSA-C, and to search for correlations between these MRI features and clinical signs. METHODS: Consecutive patients referred for SLOCA underwent comprehensive clinical evaluation and laboratory investigations, brain MRI, DaTscan and a 1-year follow-up. RESULTS: Among 80 patients, 26 had MSA-C, 22 another diagnosis, and 32 no diagnosis at the end of the follow-up. At baseline, MCP hyperintensity and HCB were more frequent in patients finally diagnosed with MSA-C than in other patients with SLOCA (p < 0.0001), and had the highest specificity (98.5%) and positive predictive value (91.7%) for the diagnosis of MSA-C, compared to all other MRI signs. The most relevant MRI sequence regarding HCB sign was the T2-proton density (DP) weighted. All MRI features were more frequent with disease duration. No correlation was found between any MRI feature and neither clinical data, nor dopaminergic neuronal loss (p = 0.5008), except between vermis atrophy and UPDRSIII score. CONCLUSION: MCP hyperintensity and HCB sign should be added into the list of additional features of possible MSA-C. MRI signal abnormalities suggestive of MSA-C should be searched for in suitable sequence.

Deciphering the causes of sporadic late-onset cerebellar ataxias: a prospective study with implications for diagnostic work.

The management of sporadic late-onset cerebellar ataxias represents a very heterogeneous group of patients and remains a challenge for neurologist in clinical practice. We aimed at describing the different causes of sporadic late-onset cerebellar ataxias that were diagnosed following standardized, exhaustive investigations and the population characteristics according to the aetiologies as well as at evaluating the relevance of these investigations. All patients consecutively referred to our centre due to sporadic, progressive cerebellar ataxia occurring after 40 years of age were included in the prospective, observational study. 80 patients were included over a 2 year period. A diagnosis was established for 52 patients (65%) corresponding to 18 distinct causes, the most frequent being cerebellar variant of multiple system atrophy (n = 29). The second most frequent cause was inherited diseases (including spinocerebellar ataxias, late-onset Friedreich's disease, SLC20A2 mutations, FXTAS, MELAS, and other mitochondrial diseases) (n = 9), followed by immune-mediated or other acquired causes. The group of patient without diagnosis showed a slower worsening of ataxia (p < 0.05) than patients with multiple system atrophy. Patients with later age at onset experienced faster progression of ataxia (p = 0.001) and more frequently parkinsonism (p < 0.05) than patients with earlier onset. Brain MRI, DaT scan, genetic analysis and to some extent muscle biopsy, thoracic-abdominal-pelvic tomodensitometry, and cerebrospinal fluid analysis were the most relevant investigations to explore sporadic late-onset cerebellar ataxia. Sporadic late-onset cerebellar ataxias should be exhaustively investigated to identify the underlying causes that are numerous, including inherited causes, but dominated by multiple system atrophy.