N-Acetyl Cysteine and Curcumin in Pediatric Acute-Onset Neuropsychiatric Syndrome

A girl aged 3 years and 4 months presented with obsessive-compulsive disorder (OCD) and tics. Initial onset occurred suddenly at 2 years and followed an impetigo infection.

The initial tic was repetitive blinking, which later increased in complexity to include sniffing, shrugging, and throwing her arm out. She had high anxiety and poor social interaction with other children. This patient met the diagnostic criteria for pediatric acute-onset neuropsychiatric syndrome (PANS) as set out by Swedo et al. (2012) with sudden onset OCD, plus anxiety, extreme irritability, and bouts of aggression. The diagnostic criteria stipulate that the OCD symptoms must be sufficient to meet the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV) criteria.

Her mother reported that the OCD symptoms were of primary concern as it would set off extreme behavior. The mother feared doing anything in case it set her off. The child was extremely sensitive to touch.

The mother had previously consulted with an integrative general practitioner who had prescribed zinc picolinate 15 mg/day, multistrain probiotic, N-acetyl cysteine (N-AC) 600 mg/day, digestive enzymes (betaine hydrochloride 480 mg, l-glutamic acid 480 mg, pancreatin 140 mg, Ox bile concentrate 80 mg, and pepsin 70 mg) and conifer green pine needle extract 320 mg twice daily. Previous investigations revealed negative Streptococcus A serology, normal C-reactive protein plus mildly elevated serum albumin. This may indicate inflammation but is nonspecific.

There had been mild improvement in tics but had continued to experience substantial OCD symptoms. The Yale Global Tic Severity Scale (YGTSS) and Children's Yale-Brown Obsessive Scale (CY-BOCS) were administered by the primary clinician to assess severity and establish baseline scores (shown in Table 1a). As it was administered in a primary care setting, the clinician was not blinded.

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Table 1.

Baseline (a) and Post-Treatment (b) Scores for Obsessive Compulsive Disorder Assessed by the Children's Yale-Brown Obsessive Scale and Tics Assessed by The Yale Global Tic Severity Scale After 3 Weeks of Treatment of 90 mg Curcumin and 1800 mg N-Acetyl Cysteine Daily in a 3-Year-Old Patient with Pediatric Acute-Onset Neuropsychiatric Syndrome

(a) Baseline		(b) Post-treatment		Difference	%
CY-BOCS total	30	CY-BOCS total	13	−17	−57
Total YGTSS	62	Total YGTSS	10	−52	−84

CY-BOCS, Children's Yale-Brown Obsessive Scale; YGTSS, The Yale Global Tic Severity Scale.

Written consent for the case report was obtained from both parents.

Intervention: the patient was prescribed curcumin 90 mg/day (as phospholipid complex) and dose of N-AC was increased from 600 to 1800 mg per day.

Within 7 days, the mother reported almost complete remission of symptoms. The child has been very affectionate and happy, seemed much less sensitive to touch and much generally calmer.

A follow-up 3 weeks later showed a significant reduction in both OCD and tics as shown in Table 1b. CY-BOCS showed a 17-point reduction, taking the OCD severity from severe to mild. The 52-point reduction in YGTSS represented an 84% reduction in the tic disorder.

A systematic review supported the use of N-AC in presentations of moderate-severity OCD. Oliver et al. (2015) found that doses of 2400–3000 mg/day for a minimum of 8 weeks may be adequate for exerting an initial therapeutic effect. N-AC is well tolerated in pediatric cases with minimal adverse effects of flatulence, headaches, skin rash, and nausea.

Curcumin has been well documented to exert both upregulation of antioxidant pathway Nrf2/ARE (nuclear-like factor 2/antioxidant response element) and inhibiting inflammatory mediators, most notably nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) (Kulkarni and Dhir 2010). The combination with phospholipid complex has shown to improve the bioavailability of curcumin, a major therapeutic consideration with neurological disorders. There may also be additional therapeutic benefit to this combination as a synergistic effect has been documented between curcumin and phosphatidylserine on downregulating both interleukin-1b and microglial activation (Mercanti et al. 2014).

The case report showed a substantial reduction in OCD and tic symptoms. Given the level of improvement demonstrated, further research is urgently needed to ascertain whether these findings can be extrapolated to a wider population of children impacted by OCD, tics, and/or PANS.