Manual Novel Approaches to Studying Basal Ganglia and Related Neuropsychiatric Disorders

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Among the infection-linked disorders, rheumatic fever RF and Sydenham chorea SC are the most widely defined and well-known disorders. More recently, a condition has been related to streptococcal infection: the pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection and registered as the PANDAS acronym. This condition was first reported by Swedo et al. The definition of CANS requires only the acute dramatic onset of OCD and other associated neuropsychiatric disturbances [ 7 , 9 , 11 ].

Auto-antibodies might be responsible for targeting brain structures, such as dopamine D1 and D2 receptors, leading to the alteration of dopaminergic transmission [ 12 ]. Dale et al. However, these authors [ 13 ] concluded that assessment of D2 receptor antibodies may be useful in defining autoimmune movement and psychiatric disorders. As reported by Dale et al. The etiological events causing the disorder are not always detectable; therefore no guideline for treating patients is homogeneously recognized.


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According to that, the treatment can be differently graded according to the degree of the symptoms mild, moderate, serious, severe. In some children, the use of antibiotics may be justified to prevent new infections in association with anti-inflammatories like naproxen and corticosteroids; in the more severe cases, use of cycles of intravenous immunoglobulin IVIG , plasmapheresis PEX , and monoclonal antibodies Rituximab has been advanced [ 14 ].

Clinical evidence reveals that tonsil removal has no efficacy in delaying or changing the course of the disease. Pavone et al. The results between the two groups PANDAS and control subjects showed that tonsillectomy did not reduce the severity of neuropsychiatric symptoms [ 16 ]. The present study focuses on 34 patients with a serious-severe form of PANDAS diagnosed and clinically followed by the participants to this study.

At the diagnosis, laboratory and diagnostic evaluation were carried out according to Chang et al. The patients were clinically followed up for three years. The software was created with runs in the Cloud to obtain data rapidly, and to gain even more information in further studies. A total of 34 patients include 18 males and 16 females, with an average age of 9. All patients showed at least one psychiatric manifestations, specifically anxiety, enuresis, phobia, oppositional behavior. Their daily activity was compromised, as the OCD manifested with episodes of selective feeding, eating refusal, excessive food intake, and behavioral disorders such as psychosis, suicidal thoughts, aggression, and self- harm.

The tics were motor and phonic types, both simple and complex: eye blinking, whistling, shoulder shrugs, facial grimaces, pulling at clothes, jumping, sniffing, throat cleansing, coughing, and spitting. Choreiform movements were found in three patients, and they were largely localized in the arms. In Tables , the single clinical features and psychiatric manifestations are reported. Pharyngeal swab was as positive in 28 children, 4 negative in 4 children, and not available in 2 children. The ASO and the Anti-DNase B titers are higher comparing to the average data from other centers, these discordances may be due to the different strains of involved streptococci.

Psychiatric Neuroimaging Division - Massachusetts General Hospital, Boston, MA

The EEG was normal in almost all cases, with exceptions in three consisting of basal rhythmic asymmetry. The ECG and cardiac ultrasound were normal in all patients. Brain MRI showed abnormalities in 3 cases: a mild asymmetry of the lateral ventricles in two cases, prevalently left asymmetry and a mild bilateral enlargement of the perioptical sheath in one. The remaining cases showed normal. All patients showed impressive tics in high frequency which tends to vary in intensity during the time, and OCD symptoms not responsive to treatment with antibiotics. Gender played no role in the results obtained.

In this cohort with serious-severe PANDAS, choreiform movements were not constantly noted, however, they were largely localized in the arms when they were present. The pharyngeal swab analyses were quite informative. IVIG treatment seems to be useful in the most severe cases.

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The course is variable with different phases, depending on the re-appearance of new infection [ 1 - 5 ]. Therefore, a differential diagnosis between the two disorders is difficult to be performed. This represents an exciting gap that future research will be able to bridge. As reported by Spinello et al. Owing to the high prevalence of the disease about 6. We argue here that to strengthen our understanding of the wide spectrum and variability of PD motor symptoms we need to address how dopamine dysregulation reverberates on the whole BG—Ctx—Cer system.

This broader perspective allows for understanding the dopamine-related causes of PD symptoms as linked to the circular dynamic relations involving the meso-level multiple circuits within BG, Cer and Ctx and their reciprocal interactions at the level of the whole system. This perspective also supports the identification of new possible disease monitoring processes and therapeutic interventions, for example, the identification of new targets for DBS and TMS, a model-based guidance of brain imaging techniques to follow the disease evolution, and a more informed solution of drug-related side effects concerning psychiatric and cognitive disorders.

Davie, C. Redgrave, P.

Novel Approaches to Studying Basal Ganglia and Related Neuropsychiatric Disorders

Goal-directed and habitual control in the basal ganglia: implications for Parkinson's disease. Obeso, J. Missing pieces in the Parkinson's disease puzzle. Wiecki, T. Brain Res. Yin, H.

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The role of the basal ganglia in habit formation. Bostan, A. Cerebellar networks with the cerebral cortex and basal ganglia. Trends Cogn. Caligiore, D. The contribution of brain sub-cortical loops in the expression and acquisition of action understanding abilities.

Early Life Stress, Depression And Parkinson’s Disease: A New Approach

The Cerebellum Alexander, G. Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Middleton, F. Basal ganglia output and cognition: evidence from anatomical, behavioral, and clinical studies. Brain Cogn. Ichinohe, N.


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A di-synaptic projection from the lateral cerebellar nucleus to the laterodorsal part of the striatum via the central lateral nucleus of the thalamus in the rat. Hoshi, E. The cerebellum communicates with the basal ganglia. The basal ganglia communicate with the cerebellum. Natl Acad. Sci USA , — Pelzer, E. Cerebellar networks with basal ganglia: feasibility for tracking cerebello-pallidal and subthalamo-cerebellar projections in the human brain. Milardi, D. Alegre, M. Cattaneo, L. Your actions in my cerebellum: Subclinical deficits in action observation in patients with unilateral chronic cerebellar stroke.

Cerebellum 11 , — Mc Cairn, K. Global dysrhythmia of cerebro-basal ganglia-cerebellar networks underlies motor tics following striatal disinhibition. Filip, P. Dystonia and the cerebellum: a new field of interest in movement disorders?

Helmich, R. Cerebral causes and consequences of parkinsonian resting tremor: A tale of two circuits? Brain , — Wu, T. The cerebellum in Parkinson's disease. Jahanshahi, M. Self-initiated versus externally triggered movements. Connolly, B. Pharmacological treatment of Parkinson's disease: a review. Moustafa, A. Neural and behavioral substrates Parkinson's disease.

Owen, A. Neuroscientist 10 , — Ray, N. Pallidal dysfunction drives a cerebellothalamic circuit into Parkinson tremor.

Shine, J. Maillet, A. Brain Mapp.