Gut Microbiome and Serum Metabolome Alterations Associated with Isolated Dystonia.

Dystonia is a complex neurological movement disorder characterized by involuntary muscle contractions. Increasing studies implicate the microbiome as a possible key susceptibility factor for neurological disorders, but the relationship between the gut microbiota and dystonia remains poorly explored. Here, the gut microbiota of 57 patients with isolated dystonia and 27 age- and environment-matched healthy controls was analyzed by 16S rRNA gene amplicon sequencing. Further, integrative analysis of the gut microbiome and serum metabolome measured by high-performance liquid chromatography-mass spectrometry was performed. No difference in α-diversity was found, while ß-diversity was significantly different, with a more heterogeneous community structure among dystonia patients than among controls. The most significant changes in dystonia highlighted an increase in Clostridiales, including Blautia obeum, Dorea longicatena, and Eubacterium hallii, and a reduction in Bacteroides vulgatus and Bacteroides plebeius. The functional analysis revealed that genes related to tryptophan and purine biosynthesis were more abundant in gut microbiota from patients with dystonia, while genes linked to citrate cycle, vitamin B6, and glycan metabolism were less abundant. The evaluation of serum metabolites revealed altered levels of l-glutamic acid, taurine, and d-tyrosine, suggesting changes in neurotransmitter metabolism. The most modified metabolites strongly inversely correlated with the abundance of members belonging to the Clostridiales, revealing the effect of the gut microbiota on neurometabolic activity. This study is the first to reveal gut microbial dysbiosis in patients with isolated dystonia and identified potential links between gut microbiota and serum neurotransmitters, providing new insight into the pathogenesis of isolated dystonia. IMPORTANCE Dystonia is the third most common movement disorder after essential tremor and Parkinson's disease. However, the cause for the majority of cases is not known. This is the first study so far that reveals significant alterations of gut microbiome and correlates the alteration of serum metabolites with gut dysbiosis in patients with isolated dystonia. We demonstrated a general overrepresentation of Clostridiales and underrepresentation of Bacteroidetes in patients with dystonia in comparison with healthy controls. The functional analysis found that genes related to the biosynthesis of tryptophan, which is the precursor of the neurotransmitter serotonin, were more active in isolated dystonia patients. Altered levels of several serum metabolites were found to be associated with microbial changes, such as d-tyrosine, taurine, and glutamate, indicating differences in neurotransmitter metabolism in isolated dystonia. Integrative analysis suggests that neurotransmitter system dysfunction may be a possible pathway by which the gut microbiome participates in the development of dystonia. The gut microbiome changes provide new insight into the pathogenesis of dystonia, suggesting new potential therapeutic directions.

Acute neurological involvement in diarrhea-associated hemolytic uremic syndrome.

BACKGROUND AND OBJECTIVES: Neurologic involvement is the most threatening complication of diarrhea-associated hemolytic uremic syndrome (D+HUS). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We report a retrospective multicenter series of 52 patients with severe initial neurologic involvement that occurred in the course of D+HUS. RESULTS: Verotoxigenic Escherichia coli infection was documented in 24. All except two patients had acute renal failure that required peritoneal dialysis, hemodialysis, or both techniques. A first group of eight patients remained with normal consciousness; five of them had protracted seizures. A second group of 23 patients had stuporous coma; five of these had protracted severe seizures, and 18 had a neurologic defect including pyramidal syndrome, hemiplegia or hemiparesia, and extrapyramidal syndrome. A third group of 21 patients had severe coma. Plasma exchanges were undertaken in 25 patients, 11 of whom were treated within 24 hours after the first neurologic sign; four died, two survived with severe sequelae, and five were alive without neurologic defect. Magnetic resonance imaging (MRI) for 29 patients showed that (1) every structure of the central nervous system was susceptible to involvement; (2) no correlation seemed to exist between special profile of localization on early MRI and the final prognosis; and (3) MRI did not exhibit any focal lesions in three patients. The overall prognosis of the series was marked by the death of nine patients and severe sequelae in 13. CONCLUSIONS: Neurologic involvement is associated with a severe renal disease but does not lead systematically to death or severe disability.

Treatment of dystonia in striatal necrosis caused by Mycoplasma pneumoniae.

We report on an 8-year-old male with bilateral striatal necrosis secondary to Mycoplasma pneumoniae respiratory infection. This patient has been remarkable for persistent severe dystonia that has been difficult to treat. We share our experience of beneficial responses to multimodal treatment, including moderate doses of trihexyphenidyl, botulinum toxin, and intrathecal baclofen.

Focal limb dystonia in a patient with a cerebellar mass.

BACKGROUND: Focal dystonia of acute onset is indicative of a structural lesion in the nervous system. Cerebellar lesions have rarely been associated with dystonia. CASE DESCRIPTION: A 42-year-old woman was admitted to the neurology ward because of fever, confusion, and gait unsteadiness. She was diagnosed as having tuberculous meningitis, and, after a few days of antituberculous treatment, she developed prominent dystonia of the left upper limb. Cranial nuclear magnetic resonance imaging showed an isolated lesion compatible with a tuberculoma in the left cerebellar hemisphere. Both the limb dystonia and the tuberculoma resolved with maintained antituberculous treatment. CONCLUSIONS: In the patient described, the presence of upper-limb dystonia ipsilateral to a focal cerebellar lesion and the resolution of the dystonia and the mass lesion following treatment suggest that the cerebellum or its connections to the thalamus and/or basal ganglia could be involved in the pathophysiology of the dystonia.