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.

Unravelling the etiology of sporadic late-onset cerebellar ataxia in a cohort of 205 patients: a prospective study.

BACKGROUND: Despite recent progress in the field of genetics, sporadic late-onset (> 40 years) cerebellar ataxia (SLOCA) etiology remains frequently elusive, while the optimal diagnostic workup still needs to be determined. We aimed to comprehensively describe the causes of SLOCA and to discuss the relevance of the investigations. METHODS: We included 205 consecutive patients with SLOCA seen in our referral center. Patients were prospectively investigated using exhaustive clinical assessment, biochemical, genetic, electrophysiological, and imaging explorations. RESULTS: We established a diagnosis in 135 (66%) patients and reported 26 different causes for SLOCA, the most frequent being multiple system atrophy cerebellar type (MSA-C) (41%). Fifty-one patients (25%) had various causes of SLOCA including immune-mediated diseases such as multiple sclerosis or anti-GAD antibody-mediated ataxia; and other causes, such as alcoholic cerebellar degeneration, superficial siderosis, or Creutzfeldt-Jakob disease. We also identified 11 genetic causes in 20 patients, including SPG7 (n = 4), RFC1-associated CANVAS (n = 3), SLC20A2 (n = 3), very-late-onset Friedreich's ataxia (n = 2), FXTAS (n = 2), SCA3 (n = 1), SCA17 (n = 1), DRPLA (n = 1), MYORG (n = 1), MELAS (n = 1), and a mitochondriopathy (n = 1) that were less severe than MSA-C (p < 0.001). Remaining patients (34%) had idiopathic late-onset cerebellar ataxia which was less severe than MSA-C (p < 0.01). CONCLUSION: Our prospective study provides an exhaustive picture of the etiology of SLOCA and clues regarding yield of investigations and diagnostic workup. Based on our observations, we established a diagnostic algorithm for SLOCA.

Prevalence and characterisation of vocal fold motion impairment (VFMI) in patients with Multiple system atrophy compared with Parkinson's disease.

INTRODUCTION: Multiple system atrophy (MSA) is a neurodegenerative disorder in which vocal fold mobility can be affected, sometimes leading to life-threatening situations. Our aim was to know if laryngeal examination could help differentiate MSA from Parkinson's disease (PD). MATERIALS AND METHODS: Between 2004 to 2014, all consecutive patients diagnosed with probable MSA were included in this retrospective, monocentric study. Flexible laryngoscopy was obtained in 51 MSA patients and compared with 27 patients with Parkinson's disease (PD). Laryngeal muscles EMG was available in 6 MSA patients. RESULTS: Vocal fold motion impairments (VFMI) was found in 35 (68.6%) MSA patients: 15 (29.4%) had uni- or bilateral vocal fold abnormal movement (VFAM), 13 (25.5%) had uni- or bilateral vocal fold abductor paresis (VFABP), 4 (7.8%) had uni- or bilateral vocal fold adductor paresis (VFADP), 10 (19.6%) had bilateral vocal fold paralysis (BVFP). VFMI was found in 13 PD patients (48.1%) all of whom had VFADP. Presence of BVFP was found associated with stridor (P<0.001) and dysphagia (P=0.002). In all muscles examined in 6 MSA patients, the EMG showed neuropathic patterns. CONCLUSIONS: Our data support that VFMI may be encountered in two-thirds of MSA with a variable degree of gravity. Laryngological examination should be considered as a supplementary tool for the diagnosis and prognosis of MSA. VFMI in particular VFAM, VFABD and BVFP should be discussed as an additional possible red flag even at an early stage of MSA and could help discriminate MSA from PD.

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.

Prospective study of relevance of 123I-MIBG myocardial scintigraphy and clonidine GH test to distinguish Parkinson's disease and multiple system atrophy.

BACKGROUND: 123I-MIBG myocardial scintigraphy and clonidine growth hormone test (CGH test) may help to distinguish multiple system atrophy (MSA) from Parkinson's disease (PD). Their relevance in the first-stage parkinsonism of uncertain etiology is unknown. METHODS: Patients experiencing parkinsonism of ambiguous etiology were clinically classified into the PD group or the MSA group as initial clinical diagnosis (ICD). Then, CGH test and myocardial scintigraphy were performed. Clinical assessment was repeated throughout the disease course until the final clinical diagnosis (FCD) could be established according to the criteria of PD and MSA, respectively. RESULTS: Twenty-five patients with uncertain diagnosis were included (15 MSA and 10 PD as ICD). At the end of a 6-year follow-up, FCD was MSA in 11/25 patients and PD in 14/25. The CGH test and the scintigraphy showed a sensitivity of 82%, and a specificity of 71 and 93%, respectively, for the diagnosis of MSA. The combination of a normal scintigraphy (i.e., with myocardial MIBG uptake) with genitourinary dysfunction was the most relevant test to diagnose MSA, whereas an abnormal scintigraphy with a levodopa response of > 30% or an abnormal scintigraphy with the absence of OH was the most relevant combinations to diagnose PD. All these combinations had an accuracy superior than 90% and a specificity of 100%. CONCLUSION: Combinations of myocardial scintigraphy with genitourinary dysfunction, levodopa response of > 30%, or orthostatic hypotension could be of interest for the distinction between PD and MSA when the clinical diagnosis remains ambiguous at the first stage of the disease.

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.

L-2-hydroxyglutaric aciduria diagnosed in a young adult with progressive cerebellar ataxia and facial dyskinesia.

INTRODUCTION: L-2-hydroxyglutaric aciduria is a rare metabolic disorder with quite typical radiological abnormalities and various clinical symptoms. OBSERVATION: A 19-year-old girl presented with ataxia, facial dyskinesia, and mild cognitive impairment. Cerebral magnetic resonance imaging demonstrated subcortical white matter T2 abnormalities and a suggestive rim hyperintensity around the caudate nuclei and the putamen. Diagnosis was confirmed by increased 2-hydroxyglutaric acid in urine and a genetic study (Gly260Ala mutation in the L-2-hydroxyglutarate dehydrogenase (L2HGDH) gene). DISCUSSION: This case highlights the movement disorder onset and radiological aspects that should indicate the L-2-hydroxyglutaric aciduria diagnosis.

[Severe generalized dystonia due to postradiotherapy cerebral calcifications]. / Dystonie généralisée sévère liée à des calcifications cérébrales postradiques.

INTRODUCTION: Cerebral calcifications are a cause of secondary dystonia and may be an uncommon complication of radiotherapy. We report a very severe case of generalized dystonia due to postradiotherapy basal ganglia calcifications. CASE REPORT: An 8-year-old girl received 53 grays radiotherapy after surgery for craniopharyngioma. One year later she developed generalized dystonia. Computed tomography showed bilateral basal ganglia calcifications, especially of the lenticular nuclei. Pharmacological treatment with tetrabenazine, clonazepam and trihexiphenydile allowed a very limited improvement of dystonia; the course was complicated by dystonic storms and decompensations resulting from the iatrogenous panhypopituitarism. CONCLUSION: This case illustrates a severe complication of cranial irradiation which should be considered in the indications of this treatment, especially for children.