PANDAS and the immunologic hypothesis in the obsessive-compulsive disorder

LETTERS TO THE EDITORS

Letter 2: PANDAS and the immunologic hypothesis in the obsessive-compulsive disorder

PANDAS y la hipótesis inmunológica en el trastorno obsesivo-compulsivo

Dear Editor,

We read with great interest the article submitted by Ronchetti et al.¹ discussing the subject of PANDAS, which is an acronym for pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection, and which describes a subset of patients with obsessive-compulsive disorder (OCD) and tic disorders secondary to an auto-immune process triggered by a group A beta-hemolytic streptococci infection. The authors describe the diagnostic criteria for PANDAS as proposed by Swedo et al.² and state that "their acceptance by the scientific community is practically unanimous." In fact, not only the diagnostic criteria, but also the very existence of PANDAS as a clinical entity has been questioned most critically in the literature.^3,4 Firstly, a diagnosis of PANDAS covers, in a single category, two conditions that do not always overlap clinically, OCD and tic disorders. Pre-pubertal onset and fluctuating clinical course are both frequent occurrences in primary OCD and tic disorders cases, and do not, therefore, guarantee the specificity of PANDAS diagnosis. Streptococcal infections are very common among schoolchildren and it is difficult to establish unequivocal causal relationship between these infections and OCD and tic disorders. Furthermore, the definition of neurological indicators present in PANDAS cases is generic and there are no established limits between choreiform movements and chorea itself. It should also be pointed out that the presence of chorea would define a diagnosis of Sydenham's chorea, thus ruling out a diagnosis of PANDAS. Finally, if PANDAS were to be an alternative manifestation of rheumatic fever, as was proposed, then carditis, migratory polyarthritis and cutaneous abnormalities, such as erythema marginatum and subcutaneous nodules, should also be observed in PANDAS cases, which does not happen.

The pathophysiology of PANDAS, as Ronchetti et al.¹ point out, is based on the Sydenham's chorea model, in which it is postulated that there is a crossover reaction between anti-streptococcal antibodies and the basal nuclei, resulting in dysfunction of the circuits linking striatum, globus pallidus, thalamus and cortex. There is no evidence, however, that these auto-antibodies provoke an inflammatory response from the basal nuclei in patients with Sydenham's chorea, as the authors claim. In the past anatomopathological studies of Sydenham's chorea demonstrated inflammation of the basal nuclei, but these studies were later questioned because the inflammation is not restricted to these structures and could be better explained by ischaemia resulting from severe heart failure associated with these patients' rheumatic carditis.⁵ Recent neuroimaging studies demonstrate basal nuclei involvement in Sydenham's chorea, but merely revealed differences in the average dimensions of these structures between patient and control groups, while there was a great deal of intra-group variation and inter-group overlap. These studies did not find any abnormalities in the blood-brain barrier, which is an important marker of central nervous system inflammation for patients with Sydenham's chorea, with the exception of isolated case histories.⁵ A classic method for studying central nervous system inflammation is by cerebrospinal fluid analysis and this too failed to reveal abnormalities among patients with Sydenham's chorea.⁵

It is important to emphasize that, with current knowledge of PANDAS in the state it is, there is no evidence to justify the routine employment of microbiological/serological tests, nor the use of antimicrobial/immunomodulatory therapy with children suffering from OCD and/or tic disorders.^3,4

REFERENCES

1. Ronchetti R, Böhme ES, Ferrão YA. A hipótese imunológica no transtorno obsessivo-compulsivo: revisão de um subtipo (PANDAS) com manifestação na infância. R Psiquiatr RS 2004;26(1):62-9.

2. Swedo SE, Leonard HL, Garvey M, et al. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases. Am J Psychiatry 1998;155:264-71.

3. Singer HS, Loiselle C. PANDAS: a commentary. J Psychosom Res 2003;55:31-9.

4. Kurlan R. The PANDAS hypothesis: losing its bite? Mov Disord 2004;19(4):371-4.

5. Cardoso F. Infectious and transmissible movement disorders. In: Jankovic J, Tolosa E, eds. Parkinson's disease and movement disorders. Philadelphia: Lippincott-Williams and Wilkins; 2002. pp. 584-95.

Antônio L. Teixeira Jr.

Professor, Department of Medical Practice, School of Medicine, Universidade Federal de Minas Gerais (UFMG), Brazil.

Publication Dates

• Publication in this collection
  13 Sept 2005
• Date of issue
  Aug 2004