Diagnosis and Treatment of Catatonia in Autism: Cerebrospinal Fluid Neurotransmitter Findings and Treatment Response; Role for New Therapeutic Options

Background: Patients with autism have been described as developing movement disorders of catatonic type. In addition autism has rarely been associated with central folate deficiency with motor problems in early childhood. Traditional reviews in the literature have not evaluated for possible neurotransmitter problems. Treatments have been limited to either lorazepam or electroconvulsive treatments in the past. We describe the presence of various neurotransmitter abnormalities in 6 patients and their response to folinic acid and/or dopamine replacement therapy.

Objectives:

Patients with autism have been described as developing catatonia but rarely studied for neurotransmitter deficiency. In six cases, lumbar spinal fluid was collected to evaluate the possibility of defective neurotransmitter or folate metabolism. Patients all had normal neuroimaging studies on 1.5 tessla MRI.

Methods: Lumbar cerebrospinal fluid (CSF) was collected under defined conditions from 6 male patients (ages 11,13, 14(2),15, 17 years) with autism and catatonia.   Two patients also had brain nuclear medicine SPECT brain scans and all had 1.5 Tesla MRI brain imaging, reported as normal in all patients. CSF was analyzed for neurotransmitter metabolites homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) and 5-methyltetrahydrofolate (5MTHF) using HPLC and electrochemical detection. Comparison data in other younger non-catatonic autistic children who had CSF data showed no neurotransmitter metabolite abnormality ( N=12) and are used as a control group.Treatment outcomes are described using either folinic acid or levodopa/carbidopa.

Results:

Three patients showed low abnormal metabolite levels. The two most severely catatonic patients  had low HVA (49;139 reference range 167-563 nmol/l) and low 5-HIAA (34; reference range 67-189 nmol/l) and borderline 5MTHF (44; reference range 40-150 nmol/l). A second patient had a low CSF 5-MTHF level of 29nmol/l. A third patient with dystonic gait onset showed low 5HIAA levels only (65; reference range 67-189 nmol/l). Another 2 patients had high 5-HIAA levels. Treatment with folinic acid at 10-20mg BID led to clinical improvement in 4/6 patients and levodopa/carbidopa supplementation in addition helped 2 patients with low HVA or 5-HIAA.

Conclusions: These patients with autism had late childhood or adolescent regressions with onset of catatonia. The presence of abnormal levels of neurotransmitter metabolites or 5MTHF in 5 of these patients, together with a clinical response to folinic acid or dopamine replacement therapy, suggests that changes in these areas of metabolism may be frequent in this patient population. Non-catatonic younger children with autism do not have these findings.  A larger study is warranted to determine if the appearance of catatonia in individuals with autism may be the clinical manifestation of an underlying developmental or aquired neurotransmitter disorder.